Most-cited articles · 2019

The 100 most-cited articles in Molecules, 2019

Ranked by OpenAlex citation count on 29 October 2026, out of 4,626 eligible articles Molecules published in 2019. Ranks are frozen; this page will not change. Number one, with 2,268 citations: Oxidative Stress: A Key Modulator in Neurodegenerative Diseases.

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2026-10-29

The most-cited articles from Molecules in 2019 cluster around a few broad themes. Antioxidant and oxidative stress research features prominently, including the top paper, "Oxidative Stress: A Key Modulator in Neurodegenerative Diseases" by Singh, Kukreti, Saso and colleagues with 2268 citations. Plant polyphenols and their roles under abiotic stress, as well as natural compounds such as quercetin, curcumin, and kaempferol, also appear frequently near the top. Nanoscience and nanotechnology form another recurring theme, spanning applications from nanomedicine to plant growth and crop protection.

Readers can use this ranked list to identify the 2019 Molecules articles that have attracted the most citation attention according to OpenAlex. The list reflects citation counts among 4626 eligible articles and covers reviews and research spanning medicinal chemistry, natural products, materials, and agricultural science.

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  1. 1
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    Oxidative Stress: A Key Modulator in Neurodegenerative Diseases

    Anju Singh, Ritushree Kukreti, Luciano Saso, Shrikant Kukreti

    2,268 citationsOpen access (CC-BY)doi:10.3390/molecules24081583OpenAlex

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    Oxidative stress is proposed as a regulatory element in ageing and various neurological disorders. The excess of oxidants causes a reduction of antioxidants, which in turn produce an oxidation-reduction imbalance in organisms. Paucity of the antioxidant system generates oxidative-stress, characterized by elevated levels of reactive species (oxygen, hydroxyl free radical, and so on). Mitochondria play a key role in ATP supply to cells via oxidative phosphorylation, as well as synthesis of essential biological molecules. Various redox reactions catalyzed by enzymes take place in the oxidative phosphorylation process. An inefficient oxidative phosphorylation may generate reactive oxygen species (ROS), leading to mitochondrial dysfunction. Mitochondrial redox metabolism, phospholipid metabolism, and proteolytic pathways are found to be the major and potential source of free radicals. A lower concentration of ROS is essential for normal cellular signaling, whereas the higher concentration and long-time exposure of ROS cause damage to cellular macromolecules such as DNA, lipids and…

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    Response of Phenylpropanoid Pathway and the Role of Polyphenols in Plants under Abiotic Stress

    Anket Sharma, Babar Shahzad, Abdul Rehman, Renu Bhardwaj, Marco Landi and 1 more

    2,062 citationsOpen access (CC-BY)doi:10.3390/molecules24132452OpenAlex

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    Phenolic compounds are an important class of plant secondary metabolites which play crucial physiological roles throughout the plant life cycle. Phenolics are produced under optimal and suboptimal conditions in plants and play key roles in developmental processes like cell division, hormonal regulation, photosynthetic activity, nutrient mineralization, and reproduction. Plants exhibit increased synthesis of polyphenols such as phenolic acids and flavonoids under abiotic stress conditions, which help the plant to cope with environmental constraints. Phenylpropanoid biosynthetic pathway is activated under abiotic stress conditions (drought, heavy metal, salinity, high/low temperature, and ultraviolet radiations) resulting in accumulation of various phenolic compounds which, among other roles, have the potential to scavenge harmful reactive oxygen species. Deepening the research focuses on the phenolic responses to abiotic stress is of great interest for the scientific community. In the present article, we discuss the biochemical and molecular mechanisms related to the activation of…

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    The History of Nanoscience and Nanotechnology: From Chemical–Physical Applications to Nanomedicine

    Samer Bayda, Muhammad Adeel, Tiziano Tuccinardi, Marco Cordani, Flavio Rizzolio

    2,024 citationsOpen access (CC-BY)doi:10.3390/molecules25010112OpenAlex

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    Nanoscience breakthroughs in almost every field of science and nanotechnologies make life easier in this era. Nanoscience and nanotechnology represent an expanding research area, which involves structures, devices, and systems with novel properties and functions due to the arrangement of their atoms on the 1-100 nm scale. The field was subject to a growing public awareness and controversy in the early 2000s, and in turn, the beginnings of commercial applications of nanotechnology. Nanotechnologies contribute to almost every field of science, including physics, materials science, chemistry, biology, computer science, and engineering. Notably, in recent years nanotechnologies have been applied to human health with promising results, especially in the field of cancer treatment. To understand the nature of nanotechnology, it is helpful to review the timeline of discoveries that brought us to the current understanding of this science. This review illustrates the progress and main principles of nanoscience and nanotechnology and represents the pre-modern as well as modern timeline era of…

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    Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application

    Dong Wu Xu, Meng-Jiao Hu, Yan-Qiu Wang, Yuan‐Lu Cui

    1,305 citationsOpen access (CC-BY)doi:10.3390/molecules24061123OpenAlex

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    Quercetin is a bioactive compound that is widely used in botanical medicine and traditional Chinese medicine due to its potent antioxidant activity. In recent years, antioxidant activities of quercetin have been studied extensively, including its effects on glutathione (GSH), enzymatic activity, signal transduction pathways, and reactive oxygen species (ROS) caused by environmental and toxicological factors. Chemical studies on quercetin have mainly focused on the antioxidant activity of its metal ion complexes and complex ions. In this review, we highlight the recent advances in the antioxidant activities, chemical research, and medicinal application of quercetin.

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    Applications of Nanotechnology in Plant Growth and Crop Protection: A Review

    Yifen Shang, Md. Kamrul Hasan, Golam Jalal Ahammed, Mengqi Li, Hanqin Yin and 1 more

    1,253 citationsOpen access (CC-BY)doi:10.3390/molecules24142558OpenAlex

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    In the era of climate change, global agricultural systems are facing numerous, unprecedented challenges. In order to achieve food security, advanced nano-engineering is a handy tool for boosting crop production and assuring sustainability. Nanotechnology helps to improve agricultural production by increasing the efficiency of inputs and minimizing relevant losses. Nanomaterials offer a wider specific surface area to fertilizers and pesticides. In addition, nanomaterials as unique carriers of agrochemicals facilitate the site-targeted controlled delivery of nutrients with increased crop protection. Due to their direct and intended applications in the precise management and control of inputs (fertilizers, pesticides, herbicides), nanotools, such as nanobiosensors, support the development of high-tech agricultural farms. The integration of biology and nanotechnology into nonosensors has greatly increased their potential to sense and identify the environmental conditions or impairments. In this review, we summarize recent attempts at innovative uses of nanotechnologies in agriculture…

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    Antioxidants of Natural Plant Origins: From Sources to Food Industry Applications

    Sofia C. Lourenço, Margarida Moldão‐Martins, Vitor Delgado Alves

    1,155 citationsOpen access (CC-BY)doi:10.3390/molecules24224132OpenAlex

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    In recent years, great interest has been focused on using natural antioxidants in food products, due to studies indicating possible adverse effects that may be related to the consumption of synthetic antioxidants. A variety of plant materials are known to be natural sources of antioxidants, such as herbs, spices, seeds, fruits and vegetables. The interest in these natural components is not only due to their biological value, but also to their economic impact, as most of them may be extracted from food by-products and under-exploited plant species. This article provides an overview of current knowledge on natural antioxidants: their sources, extraction methods and stabilization processes. In addition, recent studies on their applications in the food industry are also addressed; namely, as preservatives in different food products and in active films for packaging purposes and edible coatings.

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    Curcumin: Biological, Pharmaceutical, Nutraceutical, and Analytical Aspects

    Raghavendhar R. Kotha, Devanand L. Luthria

    894 citationsOpen access (CC-BY)doi:10.3390/molecules24162930OpenAlex

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    Turmeric is a curry spice that originated from India, which has attracted great interest in recent decades because it contains bioactive curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin). Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione), a lipophilic polyphenol may work as an anticancer, antibiotic, anti-inflammatory, and anti-aging agent as suggested by several in vitro, in vivo studies and clinical trials. However, poor aqueous solubility, bioavailability, and pharmacokinetic profiles limit curcumin's therapeutic usage. To address these issues, several curcumin formulations have been developed. However, suboptimal sample preparation and analysis methodologies often hamper the accurate evaluation of bioactivities and their clinical efficacy. This review summarizes recent research on biological, pharmaceutical, and analytical aspects of the curcumin. Various formulation techniques and corresponding clinical trials and in vivo outcomes are discussed. A detailed comparison of different sample preparation (ultrasonic, pressurized liquid…

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    Antibacterial Activity of Terpenes and Terpenoids Present in Essential Oils

    Aline Cristina Guimarães, Leandra Martins Meireles, Mayara Fumiere Lemos, Marco César Cunegundes Guimarães, Denise Coutinho Endringer and 2 more

    825 citationsOpen access (CC-BY)doi:10.3390/molecules24132471OpenAlex

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    Background: The antimicrobial activity of essential oils has been reported in hundreds of studies, however, the great majority of these studies attribute the activity to the most prevalent compounds without analyzing them independently. Therefore, the aim was to investigate the antibacterial activity of 33 free terpenes commonly found in essential oils and evaluate the cellular ultrastructure to verify possible damage to the cellular membrane. Methods: Screening was performed to select substances with possible antimicrobial activity, then the minimal inhibitory concentrations, bactericidal activity and 24-h time-kill curve studies were evaluated by standard protocols. In addition, the ultrastructure of control and death bacteria were evaluated by scanning electron microscopy. Results: Only 16 of the 33 compounds had antimicrobial activity at the initial screening. Eugenol exhibited rapid bactericidal action against Salmonella enterica serovar Typhimurium (2 h). Terpineol showed excellent bactericidal activity against S. aureus strains. Carveol, citronellol and geraniol presented a…

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    Kaempferol: A Key Emphasis to Its Anticancer Potential

    Muhammad Imran, Bahare Salehi, Javad Sharifi‐Rad, Tanweer Aslam Gondal, Farhan Saeed and 8 more

    819 citationsOpen access (CC-BY)doi:10.3390/molecules24122277OpenAlex

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    A marked decrease in human cancers, including breast cancer, bone cancer, and cervical cancer, has been linked to the consumption of vegetable and fruit, and the corresponding chemoprotective effect has been associated with the presence of several active molecules, such as kaempferol. Kaempferol is a major flavonoid aglycone found in many natural products, such as beans, bee pollen, broccoli, cabbage, capers, cauliflower, chia seeds, chives, cumin, moringa leaves, endive, fennel, and garlic. Kaempferol displays several pharmacological properties, among them antimicrobial, anti-inflammatory, antioxidant, antitumor, cardioprotective, neuroprotective, and antidiabetic activities, and is being applied in cancer chemotherapy. Specifically, kaempferol-rich food has been linked to a decrease in the risk of developing some types of cancers, including skin, liver, and colon. The mechanisms of action include apoptosis, cell cycle arrest at the G2/M phase, downregulation of epithelial-mesenchymal transition (EMT)-related markers, and phosphoinositide 3-kinase/protein kinase B signaling…

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    Isoflavones

    Ludmila Křížová, Kateřina Dadáková, Jitka Kašparovská, Tomáš Kašparovský

    695 citationsOpen access (CC-BY)doi:10.3390/molecules24061076OpenAlex

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    Phytoestrogens are naturally occurring nonsteroidal phenolic plant compounds that, due to their molecular structure and size, resemble vertebrate steroids estrogens. This review is focused on plant flavonoids isoflavones, which are ranked among the most estrogenic compounds. The main dietary sources of isoflavones for humans are soybean and soybean products, which contain mainly daidzein and genistein. When they are consumed, they exert estrogenic and/or antiestrogenic effects. Isoflavones are considered chemoprotective and can be used as an alternative therapy for a wide range of hormonal disorders, including several cancer types, namely breast cancer and prostate cancer, cardiovascular diseases, osteoporosis, or menopausal symptoms. On the other hand, isoflavones may also be considered endocrine disruptors with possible negative influences on the state of health in a certain part of the population or on the environment. This review deals with isoflavone classification, structure, and occurrence, with their metabolism, biological, and health effects in humans and animals, and with…

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    Antibacterial Properties of Propolis

    Izabela Przybyłek, Tomasz M. M Karpiński

    683 citationsOpen access (CC-BY)doi:10.3390/molecules24112047OpenAlex

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    Researchers are continuing to discover all the properties of propolis due to its complex composition and associated broad spectrum of activities. This review aims to characterize the latest scientific reports in the field of antibacterial activity of this substance. The results of studies on the influence of propolis on more than 600 bacterial strains were analyzed. The greater activity of propolis against Gram-positive bacteria than Gram-negative was confirmed. Moreover, the antimicrobial activity of propolis from different regions of the world was compared. As a result, high activity of propolis from the Middle East was found in relation to both, Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) strains. Simultaneously, the lowest activity was demonstrated for propolis samples from Germany, Ireland and Korea.

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    Recent Advances in Aptamer Discovery and Applications

    Yang Zhang, Bo Shiun Lai, Mario Juhas

    667 citationsOpen access (CC-BY)doi:10.3390/molecules24050941OpenAlex

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    Aptamers are short, single-stranded DNA, RNA, or synthetic XNA molecules that can be developed with high affinity and specificity to interact with any desired targets. They have been widely used in facilitating discoveries in basic research, ensuring food safety and monitoring the environment. Furthermore, aptamers play promising roles as clinical diagnostics and therapeutic agents. This review provides update on the recent advances in this rapidly progressing field of research with particular emphasis on generation of aptamers and their applications in biosensing, biotechnology and medicine. The limitations and future directions of aptamers in target specific delivery and real-time detection are also discussed.

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    Mono- and Di-Quaternized 4,4′-Bipyridine Derivatives as Key Building Blocks for Medium- and Environment-Responsive Compounds and Materials

    Raffaello Papadakis

    664 citationsOpen access (CC-BY)doi:10.3390/molecules25010001OpenAlex

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    Mono- and di-quaternized 4,4′-bipyridine derivatives constitute a family of heterocyclic compounds, which in recent years have been employed in numerous applications. These applications correspond to various disciplines of research and technology. In their majority, two key features of these 4,4′-bipyridine-based derivatives are exploited: their redox activity and their electrochromic aptitude. Contemporary materials and compounds encompassing these skeletons as building blocks are often characterized as multifunctional, as their presence often gives rise to interesting phenomena, e.g., various types of chromism. This research trend is acknowledged, and, in this review article, recent examples of multifunctional chromic materials/compounds of this class are presented. Emphasis is placed on solvent-/medium- and environment-responsive 4,4′-bipyridine derivatives. Two important classes of 4,4′-bipyridine-based products with solvatochromic and/or environment-responsive character are reviewed: viologens (i.e., N,N′-disubstituted derivatives) and monoquats (i.e., monosubstituted…

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    Hydrogels and Their Applications in Targeted Drug Delivery

    Radhika Narayanaswamy, Vladimir P. Torchilin

    663 citationsOpen access (CC-BY)doi:10.3390/molecules24030603OpenAlex

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    Conventional drug delivery approaches are plagued by issues pertaining to systemic toxicity and repeated dosing. Hydrogels offer convenient drug delivery vehicles to ensure these disadvantages are minimized and the therapeutic benefits from the drug are optimized. With exquisitely tunable physical properties that confer them great controlled drug release features and the merits they offer for labile drug protection from degradation, hydrogels emerge as very efficient drug delivery systems. The versatility and diversity of the hydrogels extend their applications beyond targeted drug delivery also to wound dressings, contact lenses and tissue engineering to name but a few. They are 90% water, and highly porous to accommodate drugs for delivery and facilitate controlled release. Herein we discuss hydrogels and how they could be manipulated for targeted drug delivery applications. Suitable examples from the literature are provided that support the recent advancements of hydrogels in targeted drug delivery in diverse disease areas and how they could be suitably modified in very different…

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    Review of Alternative Solvents for Green Extraction of Food and Natural Products: Panorama, Principles, Applications and Prospects

    Farid Chemat, Maryline Abert Vian, Harish Karthikeyan Ravi, Boutheina Khadhraoui, Soukaina Hilali and 2 more

    646 citationsOpen access (CC-BY)doi:10.3390/molecules24163007OpenAlex

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    In recent years, almost all extraction processes in the perfume, cosmetic, pharmaceutical, food ingredients, nutraceuticals, biofuel and fine chemical industries rely massively on solvents, the majority of which have petroleum origins. The intricate processing steps involved in the industrial extraction cycle makes it increasingly difficult to predict the overall environmental impact; despite the tremendous energy consumption and the substantial usage of solvents, often the yields are indicated in decimals. The ideal alternative solvents suitable for green extraction should have high solvency, high flash points with low toxicity and low environmental impacts, be easily biodegradable, obtained from renewable (non-petrochemical) resources at a reasonable price and should be easy to recycle without any deleterious effect to the environment. Finding the perfect solvent that meets all the aforementioned requirements is a challenging task, thus the decision for the optimum solvent will always be a compromise depending on the process, the plant and the target molecules. The objective of…

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    Selenium–Fascinating Microelement, Properties and Sources in Food

    Marek Kieliszek

    602 citationsOpen access (CC-BY)doi:10.3390/molecules24071298OpenAlex

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    Selenium is a micronutrient that is essential for the proper functioning of all organisms. Studies on the functions of selenium are rapidly developing. This element is a cofactor of many enzymes, for example, glutathione peroxidase or thioredoxin reductase. Insufficient supplementation of this element results in the increased risk of developing many chronic degenerative diseases. Selenium is important for the protection against oxidative stress, demonstrating the highest activity as a free radical scavenger and anti-cancer agent. In food, it is present in organic forms, as exemplified by selenomethionine and selenocysteine. In dietary supplementation, the inorganic forms of selenium (selenite and selenate) are used. Organic compounds are more easily absorbed by human organisms in comparison with inorganic compounds. Currently, selenium is considered an essential trace element of fundamental importance for human health. Extreme selenium deficiencies are widespread among people all over the world. Therefore, it is essential to supplement the deficiency of this micronutrient with…

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    Essential Oils as Antimicrobial Agents—Myth or Real Alternative?

    Katarzyna Wińska, Wanda Krystyna Mączka, Jacek Łyczko, Małgorzata Grabarczyk, Anna Czubaszek and 1 more

    591 citationsOpen access (CC-BY)doi:10.3390/molecules24112130OpenAlex

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    Herbs and the essential oils derived from them have been used from the beginning of human history for different purposes. Their beneficial properties have been applied to mask unpleasant odors, attract the attention of other people, add flavor and aroma properties to prepared dishes, perfumes, and cosmetics, etc. Herbs and essential oils (EOs) have also been used in medicine because of their biological properties, such as larvicidal action, analgesic and anti-inflammatory properties, antioxidant, fungicide, and antitumor activities, and many more. Many EOs exhibit antimicrobial properties, which is extremely important in fields of science and industry, such as medicine, agriculture, or cosmetology. Among the 250 EOs which are commercially available, about a dozen possess high antimicrobial potential. According to available papers and patents, EOs seem to be a potential alternative to synthetic compounds, especially because of the resistance that has been increasingly developed by pathogenic microorganisms. In this review we summarize the latest research studies about the most-active…

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    Hydrogels Based on Schiff Base Linkages for Biomedical Applications

    Junpeng Xu, Yi Liu, Shan‐hui Hsu

    566 citationsOpen access (CC-BY)doi:10.3390/molecules24163005OpenAlex

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    Schiff base, an important family of reaction in click chemistry, has received significant attention in the formation of self-healing hydrogels in recent years. Schiff base reversibly reacts even in mild conditions, which allows hydrogels with self-healing ability to recover their structures and functions after damages. Moreover, pH-sensitivity of the Schiff base offers the hydrogels response to biologically relevant stimuli. Different types of Schiff base can provide the hydrogels with tunable mechanical properties and chemical stabilities. In this review, we summarized the design and preparation of hydrogels based on various types of Schiff base linkages, as well as the biomedical applications of hydrogels in drug delivery, tissue regeneration, wound healing, tissue adhesives, bioprinting, and biosensors.

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    Role of Intestinal Microbiota in the Bioavailability and Physiological Functions of Dietary Polyphenols

    Kyuichi Kawabata, Yasukiyo Yoshioka, Junji Terao

    563 citationsOpen access (CC-BY)doi:10.3390/molecules24020370OpenAlex

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    Polyphenols are categorized as plant secondary metabolites, and they have attracted much attention in relation to human health and the prevention of chronic diseases. In recent years, a considerable number of studies have been published concerning their physiological function in the digestive tract, such as their prebiotic properties and their modification of intestinal microbiota. It has also been suggested that several hydrolyzed and/or fission products, derived from the catabolism of polyphenols by intestinal bacteria, exert their physiological functions in target sites after transportation into the body. Thus, this review article focuses on the role of intestinal microbiota in the bioavailability and physiological function of dietary polyphenols. Monomeric polyphenols, such as flavonoids and oligomeric polyphenols, such as proanthocyanidins, are usually catabolized to chain fission products by intestinal bacteria in the colon. Gallic acid and ellagic acid derived from the hydrolysis of gallotannin, and ellagitannin are also subjected to intestinal catabolism. These catabolites…

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    Hydrolyzed Collagen—Sources and Applications

    Arely León-López, Alejandro Morales-Peñaloza, Víctor Manuel Martínez Juárez, Apolonio Vargas‐Torres, Dimitrios I. Zeugolis and 1 more

    560 citationsOpen access (CC-BY)doi:10.3390/molecules24224031OpenAlex

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    Hydrolyzed collagen (HC) is a group of peptides with low molecular weight (3-6 KDa) that can be obtained by enzymatic action in acid or alkaline media at a specific incubation temperature. HC can be extracted from different sources such as bovine or porcine. These sources have presented health limitations in the last years. Recently research has shown good properties of the HC found in skin, scale, and bones from marine sources. Type and source of extraction are the main factors that affect HC properties, such as molecular weight of the peptide chain, solubility, and functional activity. HC is widely used in several industries including food, pharmaceutical, cosmetic, biomedical, and leather industries. The present review presents the different types of HC, sources of extraction, and their applications as a biomaterial.

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    Bacillus velezensis: A Valuable Member of Bioactive Molecules within Plant Microbiomes

    Muhammad Fazle Rabbee, Md. Sarafat Ali, Jinhee Choi, Buyng Su Hwang, Sang‐Chul Jeong and 1 more

    549 citationsOpen access (CC-BY)doi:10.3390/molecules24061046OpenAlex

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    Bacillus velezensis is an aerobic, gram-positive, endospore-forming bacterium that promotes plant growth. Numerous strains of this species have been reported to suppress the growth of microbial pathogens, including bacteria, fungi, and nematodes. Based on recent phylogenetic analysis, several Bacillus species have been reclassified as B. velezensis. However, this information has yet to be integrated into a well-organized resource. Genomic analysis has revealed that B. velezensis possesses strain-specific clusters of genes related to the biosynthesis of secondary metabolites, which play significant roles in both pathogen suppression and plant growth promotion. More specifically, B. velezensis exhibits a high genetic capacity for synthesizing cyclic lipopeptides (i.e., surfactin, bacillomycin-D, fengycin, and bacillibactin) and polyketides (i.e., macrolactin, bacillaene, and difficidin). Secondary metabolites produced by B. velezensis can also trigger induced systemic resistance in plants, a process by which plants defend themselves against recurrent attacks by virulent…

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    Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health

    Ana Karković Marković, Jelena Torić, Monika Barbarić, Cvijeta Jakobušić Brala

    538 citationsOpen access (CC-BY)doi:10.3390/molecules24102001OpenAlex

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    The Mediterranean diet and olive oil as its quintessential part are almost synonymous with a healthy way of eating and living nowadays. This kind of diet has been highly appreciated and is widely recognized for being associated with many favorable effects, such as reduced incidence of different chronic diseases and prolonged longevity. Although olive oil polyphenols present a minor fraction in the composition of olive oil, they seem to be of great importance when it comes to the health benefits, and interest in their biological and potential therapeutic effects is huge. There is a growing body of in vitro and in vivo studies, as well as intervention-based clinical trials, revealing new aspects of already known and many new, previously unknown activities and health effects of these compounds. This review summarizes recent findings regarding biological activities, metabolism and bioavailability of the major olive oil phenolic compounds-hydroxytyrosol, tyrosol, oleuropein, oleocanthal and oleacein-the most important being their antiatherogenic, cardioprotective, anticancer,…

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    Piper Species: A Comprehensive Review on Their Phytochemistry, Biological Activities and Applications

    Bahare Salehi, Zainul Amiruddin Zakaria, Rabin Gyawali, Salam Adnan Ibrahim, Jovana Rajković and 10 more

    526 citationsOpen access (CC-BY)doi:10.3390/molecules24071364OpenAlex

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    Piper species are aromatic plants used as spices in the kitchen, but their secondary metabolites have also shown biological effects on human health. These plants are rich in essential oils, which can be found in their fruits, seeds, leaves, branches, roots and stems. Some Piper species have simple chemical profiles, while others, such as Piper nigrum, Piper betle, and Piper auritum, contain very diverse suites of secondary metabolites. In traditional medicine, Piper species have been used worldwide to treat several diseases such as urological problems, skin, liver and stomach ailments, for wound healing, and as antipyretic and anti-inflammatory agents. In addition, Piper species could be used as natural antioxidants and antimicrobial agents in food preservation. The phytochemicals and essential oils of Piper species have shown strong antioxidant activity, in comparison with synthetic antioxidants, and demonstrated antibacterial and antifungal activities against human pathogens. Moreover, Piper species possess therapeutic and preventive potential against several chronic disorders.…

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    Terpene Derivatives as a Potential Agent against Antimicrobial Resistance (AMR) Pathogens

    Nik Amirah Mahizan, Shun-Kai Yang, Chew-Li Moo, Adelene Ai‐Lian Song, Chou Min Chong and 4 more

    474 citationsOpen access (CC-BY)doi:10.3390/molecules24142631OpenAlex

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    The evolution of antimicrobial resistance (AMR) in pathogens has prompted extensive research to find alternative therapeutics. Plants rich with natural secondary metabolites are one of the go-to reservoirs for discovery of potential resources to alleviate this problem. Terpenes and their derivatives comprising of hydrocarbons, are usually found in essential oils (EOs). They have been reported to have potent antimicrobial activity, exhibiting bacteriostatic and bactericidal effects against tested pathogens. This brief review discusses the activity of terpenes and derivatives against pathogenic bacteria, describing the potential of the activity against AMR followed by the possible mechanism exerted by each terpene class. Finally, ongoing research and possible improvisation to the usage of terpenes and terpenoids in therapeutic practice against AMR are discussed.

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    Aptamers Chemistry: Chemical Modifications and Conjugation Strategies

    Fadwa Odeh, Hamdi Nsairat, Walhan Alshaer, Mohammad A. Ismail, Ezaldeen Esawi and 3 more

    420 citationsOpen access (CC-BY)doi:10.3390/molecules25010003OpenAlex

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    Soon after they were first described in 1990, aptamers were largely recognized as a new class of biological ligands that can rival antibodies in various analytical, diagnostic, and therapeutic applications. Aptamers are short single-stranded RNA or DNA oligonucleotides capable of folding into complex 3D structures, enabling them to bind to a large variety of targets ranging from small ions to an entire organism. Their high binding specificity and affinity make them comparable to antibodies, but they are superior regarding a longer shelf life, simple production and chemical modification, in addition to low toxicity and immunogenicity. In the past three decades, aptamers have been used in a plethora of therapeutics and drug delivery systems that involve innovative delivery mechanisms and carrying various types of drug cargos. However, the successful translation of aptamer research from bench to bedside has been challenged by several limitations that slow down the realization of promising aptamer applications as therapeutics at the clinical level. The main limitations include the…

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    Chitosan-Based (Nano)Materials for Novel Biomedical Applications

    Gregor Kravanja, Mateja Primožič, Željko Knez, Maja Leitgeb

    416 citationsOpen access (CC-BY)doi:10.3390/molecules24101960OpenAlex

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    Chitosan-based nanomaterials have attracted significant attention in the biomedical field because of their unique biodegradable, biocompatible, non-toxic, and antimicrobial nature. Multiple perspectives of the proposed antibacterial effect and mode of action of chitosan-based nanomaterials are reviewed. Chitosan is presented as an ideal biomaterial for antimicrobial wound dressings that can either be fabricated alone in its native form or upgraded and incorporated with antibiotics, metallic antimicrobial particles, natural compounds and extracts in order to increase the antimicrobial effect. Since chitosan and its derivatives can enhance drug permeability across the blood-brain barrier, they can be also used as effective brain drug delivery carriers. Some of the recent chitosan formulations for brain uptake of various drugs are presented. The use of chitosan and its derivatives in other biomedical applications is also briefly discussed.

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    Medically Useful Plant Terpenoids: Biosynthesis, Occurrence, and Mechanism of Action

    Matthew E. Bergman, Benjamin B. Davis, Michael A. Phillips

    408 citationsOpen access (CC-BY)doi:10.3390/molecules24213961OpenAlex

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    Specialized plant terpenoids have found fortuitous uses in medicine due to their evolutionary and biochemical selection for biological activity in animals. However, these highly functionalized natural products are produced through complex biosynthetic pathways for which we have a complete understanding in only a few cases. Here we review some of the most effective and promising plant terpenoids that are currently used in medicine and medical research and provide updates on their biosynthesis, natural occurrence, and mechanism of action in the body. This includes pharmacologically useful plastidic terpenoids such as p-menthane monoterpenoids, cannabinoids, paclitaxel (taxol®), and ingenol mebutate which are derived from the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway, as well as cytosolic terpenoids such as thapsigargin and artemisinin produced through the mevalonate (MVA) pathway. We further provide a review of the MEP and MVA precursor pathways which supply the carbon skeletons for the downstream transformations yielding these medically significant natural products.

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    An Updated Review on Pharmaceutical Properties of Gamma-Aminobutyric Acid

    Dai‐Hung Ngo, Thanh‐Sang Vo

    406 citationsOpen access (CC-BY)doi:10.3390/molecules24152678OpenAlex

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    Gamma-aminobutyric acid (Gaba) is a non-proteinogenic amino acid that is widely present in microorganisms, plants, and vertebrates. So far, Gaba is well known as a main inhibitory neurotransmitter in the central nervous system. Its physiological roles are related to the modulation of synaptic transmission, the promotion of neuronal development and relaxation, and the prevention of sleeplessness and depression. Besides, various pharmaceutical properties of Gaba on non-neuronal peripheral tissues and organs were also reported due to anti-hypertension, anti-diabetes, anti-cancer, antioxidant, anti-inflammation, anti-microbial, anti-allergy, hepato-protection, reno-protection, and intestinal protection. Therefore, Gaba may be considered as potential alternative therapeutics for prevention and treatment of various diseases. Accordingly, this updated review was mainly focused to describe the pharmaceutical properties of Gaba as well as emphasize its important role regarding human health.

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    NAMI-A and KP1019/1339, Two Iconic Ruthenium Anticancer Drug Candidates Face-to-Face: A Case Story in Medicinal Inorganic Chemistry

    Enzo Alessio, Luigi Messori A

    386 citationsOpen access (CC-BY)doi:10.3390/molecules24101995OpenAlex

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    ]) are two structurally related ruthenium(III) coordination compounds that have attracted a lot of attention in the medicinal inorganic chemistry scientific community as promising anticancer drug candidates. This has led to a considerable amount of studies on their respective chemico-biological features and to the eventual admission of both to clinical trials. The encouraging pharmacological performances qualified KP1019 mainly as a cytotoxic agent for the treatment of platinum-resistant colorectal cancers, whereas the non-cytotoxic NAMI-A has gained the reputation of being a very effective antimetastatic drug. A critical and strictly comparative analysis of the studies conducted so far on NAMI-A and KP1019 allows us to define the state of the art of these experimental ruthenium drugs in terms of the respective pharmacological profiles and potential clinical applications, and to gain some insight into the inherent molecular mechanisms. Despite their evident structural relatedness, deeply distinct biological and pharmacological profiles do emerge. Overall, these two iconic ruthenium…

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    Hesperidin as a Neuroprotective Agent: A Review of Animal and Clinical Evidence

    Marziyeh Hajialyani, Mohammad Hosein Farzaei, Javier Echeverría, Seyed Mohammad Nabavi, Eugenio Uriarte and 1 more

    385 citationsOpen access (CC-BY)doi:10.3390/molecules24030648OpenAlex

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    Neuroprotection is the preservation of function and networks of neural tissues from damages caused by various agents, as well as neurodegenerative diseases such as Parkinson's, Alzheimer's, Huntington's diseases, and multiple sclerosis. Hesperidin, a flavanone glycoside, is a natural phenolic compound with a wide range of biological effects. Mounting evidence has demonstrated that hesperidin possesses inhibitory effect against development of neurodegenerative diseases. Our review discusses neuropharmacological mechanisms for preventive and therapeutic effects of hesperidin in neurodegenerative diseases. In addition, the review examines clinical evidence confirming its neuroprotective function. Various cellular and animal models specific to neurodegenerative diseases have been conducted to evaluate the underlying neuropharmacological mechanisms of hesperidin. Neuroprotective potential of this flavonoid is mediated by improvement of neural growth factors and endogenous antioxidant defense functions, diminishing neuro-inflammatory and apoptotic pathways. Despite the various preclinical…

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    Naturally Lignan-Rich Foods: A Dietary Tool for Health Promotion?

    Carmen Rodríguez‐García, Cristina Sánchez‐Quesada, Estefanía Toledo, Miguel Delgado‐Rodríguez, José Juan Gaforio

    374 citationsOpen access (CC-BY)doi:10.3390/molecules24050917OpenAlex

    Show abstract

    Dietary guidelines universally advise adherence to plant-based diets. Plant-based foods confer considerable health benefits, partly attributable to their abundant micronutrient (e.g., polyphenol) content. Interest in polyphenols is largely focused on the contribution of their antioxidant activity to the prevention of various disorders, including cardiovascular disease and cancer. Polyphenols are classified into groups, such as stilbenes, flavonoids, phenolic acids, lignans and others. Lignans, which possess a steroid-like chemical structure and are defined as phytoestrogens, are of particular interest to researchers. Traditionally, health benefits attributed to lignans have included a lowered risk of heart disease, menopausal symptoms, osteoporosis and breast cancer. However, the intake of naturally lignan-rich foods varies with the type of diet. Consequently, based on the latest humans' findings and gathered information on lignan-rich foods collected from Phenol Explorer database this review focuses on the potential health benefits attributable to the consumption of different diets…

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    Bee Venom: Overview of Main Compounds and Bioactivities for Therapeutic Interests

    Rim Wehbe, Jacinthe Frangieh, Mohamad Rima, Dany El Obeid, Jean‐Marc Sabatier and 1 more

    372 citationsOpen access (CC-BY)doi:10.3390/molecules24162997OpenAlex

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    Apitherapy is an alternate therapy that relies on the usage of honeybee products, most importantly bee venom for the treatment of many human diseases. The venom can be introduced into the human body by manual injection or by direct bee stings. Bee venom contains several active molecules such as peptides and enzymes that have advantageous potential in treating inflammation and central nervous system diseases, such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Moreover, bee venom has shown promising benefits against different types of cancer as well as anti-viral activity, even against the challenging human immunodeficiency virus (HIV). Many studies described biological activities of bee venom components and launched preclinical trials to improve the potential use of apitoxin and its constituents as the next generation of drugs. The aim of this review is to summarize the main compounds of bee venom, their primary biological properties, mechanisms of action, and their therapeutic values in alternative therapy strategies.

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    Endogenous and Exogenous Stimuli-Responsive Drug Delivery Systems for Programmed Site-Specific Release

    Ali Raza, Tahir Rasheed, Faran Nabeel, Uzma Hayat, Muhammad Bilal and 1 more

    369 citationsOpen access (CC-BY)doi:10.3390/molecules24061117OpenAlex

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    In this study, we reviewed state-of-the-art endogenous-based and exogenous-based stimuli-responsive drug delivery systems (DDS) for programmed site-specific release to overcome the drawbacks of conventional therapeutic modalities. This particular work focuses on the smart chemistry and mechanism of action aspects of several types of stimuli-responsive polymeric carriers that play a crucial role in extracellular and intracellular sections of diseased tissues or cells. With ever increasing scientific knowledge and awareness, research is underway around the globe to design new types of stimuli (external/internal) responsive polymeric carriers for biotechnological applications at large and biomedical and/or pharmaceutical applications, in particular. Both external/internal and even dual/multi-responsive behavior of polymeric carriers is considered an essential element of engineering so-called 'smart' DDS, which controls the effective and efficient dose loading, sustained release, individual variability, and targeted permeability in a sophisticated manner. So far, an array of DDS has…

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    Agro-Food Byproducts as a New Source of Natural Food Additives

    Margarida Faustino, Mariana Veiga, Pedro Sousa, Eduardo M. Costa, Sara Silva and 1 more

    362 citationsOpen access (CC-BY)doi:10.3390/molecules24061056OpenAlex

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    Nowadays, the agro-food industry generates high amounts of byproducts that may possess added value compounds with high functionality and/or bioactivity. Additionally, consumers' demand for healthier foodstuffs has increased over the last years, and thus the food industry has strived to answer this challenge. Byproducts are generally secondary products derived from primary agro-food production processes and represent an interesting and cheaper source of potentially functional ingredients, such as peptides, carotenoids, and phenolic compounds, thus promoting a circular economy concept. The existing body of work has shown that byproducts and their extracts may be successfully incorporated into foodstuffs, for instance, phenolic compounds from eggplant can be potentially used as a mulfitunctional food additive with antimicrobial, antioxidant, and food colorant properties. As such, the aim of this review is to provide insights into byproducts and their potential as new sources of foodstuffs additives.

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    Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

    Kathrin Laura Kohnen, Oliver Kayser

    355 citationsOpen access (CC-BY)doi:10.3390/molecules24040796OpenAlex

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    Tropane alkaloids (TA) are valuable secondary plant metabolites which are mostly found in high concentrations in the Solanaceae and Erythroxylaceae families. The TAs, which are characterized by their unique bicyclic tropane ring system, can be divided into three major groups: hyoscyamine and scopolamine, cocaine and calystegines. Although all TAs have the same basic structure, they differ immensely in their biological, chemical and pharmacological properties. Scopolamine, also known as hyoscine, has the largest legitimate market as a pharmacological agent due to its treatment of nausea, vomiting, motion sickness, as well as smooth muscle spasms while cocaine is the 2nd most frequently consumed illicit drug globally. This review provides a comprehensive overview of TAs, highlighting their structural diversity, use in pharmaceutical therapy from both historical and modern perspectives, natural biosynthesis in planta and emerging production possibilities using tissue culture and microbial biosynthesis of these compounds.

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    Broccoli or Sulforaphane: Is It the Source or Dose That Matters?

    Yoko Yagishita, Jed W. Fahey, Albena T. Dinkova‐Kostova, Thomas W. Kensler

    350 citationsOpen access (CC-BY)doi:10.3390/molecules24193593OpenAlex

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    There is robust epidemiological evidence for the beneficial effects of broccoli consumption on health, many of them clearly mediated by the isothiocyanate sulforaphane. Present in the plant as its precursor, glucoraphanin, sulforaphane is formed through the actions of myrosinase, a β-thioglucosidase present in either the plant tissue or the mammalian microbiome. Since first isolated from broccoli and demonstrated to have cancer chemoprotective properties in rats in the early 1990s, over 3000 publications have described its efficacy in rodent disease models, underlying mechanisms of action or, to date, over 50 clinical trials examining pharmacokinetics, pharmacodynamics and disease mitigation. This review evaluates the current state of knowledge regarding the relationships between formulation (e.g., plants, sprouts, beverages, supplements), bioavailability and efficacy, and the doses of glucoraphanin and/or sulforaphane that have been used in pre-clinical and clinical studies. We pay special attention to the challenges for better integration of animal model and clinical studies,…

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    Membrane Processes for Microplastic Removal

    Teresa Poerio, Emma Piacentini, Rosalinda Mazzei

    344 citationsOpen access (CC-BY)doi:10.3390/molecules24224148OpenAlex

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    Plastic pollution of the aquatic environment is a major concern considering the disastrous impact on the environment and on human beings. The significant and continuous increase in the production of plastics causes an enormous amount of plastic waste on the land entering the aquatic environment. Furthermore, wastewater treatment plants (WWTPs) are reported as the main source of microplastic and nanoplastic in the effluents, since they are not properly designed for this purpose. The application of advanced wastewater treatment technologies is mandatory to avoid effluent contamination by plastics. A concrete solution can be represented by membrane technologies as tertiary treatment of effluents in integrated systems for wastewater treatment, in particular, for the plastic particles with a smaller size (< 100 nm). In this review, a survey of the membrane processes applied in the plastic removal is analyzed and critically discussed. From the literature analysis, it was found that the removal of microplastic by membrane technology is still insufficient, and without the use of specially…

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    Fabrication of Electrospun Polymer Nanofibers with Diverse Morphologies

    Chenyu Wang, Jun Wang, Liangdan Zeng, Ziwen Qiao, Xiaochen Liu and 3 more

    332 citationsOpen access (CC-BY)doi:10.3390/molecules24050834OpenAlex

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    Fiber structures with nanoscale diameters offer many fascinating features, such as excellent mechanical properties and high specific surface areas, making them attractive for many applications. Among a variety of technologies for preparing nanofibers, electrospinning is rapidly evolving into a simple process, which is capable of forming diverse morphologies due to its flexibility, functionality, and simplicity. In such review, more emphasis is put on the construction of polymer nanofiber structures and their potential applications. Other issues of electrospinning device, mechanism, and prospects, are also discussed. Specifically, by carefully regulating the operating condition, modifying needle device, optimizing properties of the polymer solutions, some unique structures of core⁻shell, side-by-side, multilayer, hollow interior, and high porosity can be obtained. Taken together, these well-organized polymer nanofibers can be of great interest in biomedicine, nutrition, bioengineering, pharmaceutics, and healthcare applications.

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    Prospect of Polysaccharide-Based Materials as Advanced Food Packaging

    Aleksandra Nešić, Gustavo Cabrera‐Barjas, Suzana Dimitrijević‐Branković, Slađana Davidović, Neda R. Radovanović and 1 more

    327 citationsOpen access (CC-BY)doi:10.3390/molecules25010135OpenAlex

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    The use of polysaccharide-based materials presents an eco-friendly technological solution, by reducing dependence on fossil resources while reducing a product's carbon footprint, when compared to conventional plastic packaging materials. This review discusses the potential of polysaccharides as a raw material to produce multifunctional materials for food packaging applications. The covered areas include the recent innovations and properties of the polysaccharide-based materials. Emphasis is given to hemicelluloses, marine polysaccharides, and bacterial exopolysaccharides and their potential application in the latest trends of food packaging materials, including edible coatings, intelligent films, and thermo-insulated aerogel packaging.

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    Current Trends on Seaweeds: Looking at Chemical Composition, Phytopharmacology, and Cosmetic Applications

    Bahare Salehi, Javad Sharifi‐Rad, Ana M. L. Seca, Diana C. G. A. Pinto, Izabela Michalak and 5 more

    315 citationsOpen access (CC-BY)doi:10.3390/molecules24224182OpenAlex

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    Seaweeds have received huge interest in recent years given their promising potentialities. Their antioxidant, anti-inflammatory, antitumor, hypolipemic, and anticoagulant effects are among the most renowned and studied bioactivities so far, and these effects have been increasingly associated with their content and richness in both primary and secondary metabolites. Although primary metabolites have a pivotal importance such as their content in polysaccharides (fucoidans, agars, carragenans, ulvans, alginates, and laminarin), recent data have shown that the content in some secondary metabolites largely determines the effective bioactive potential of seaweeds. Among these secondary metabolites, phenolic compounds feature prominently. The present review provides the most remarkable insights into seaweed research, specifically addressing its chemical composition, phytopharmacology, and cosmetic applications.

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    Food-Grade Nanoemulsions: Preparation, Stability and Application in Encapsulation of Bioactive Compounds

    Qingqing Liu, He Huang, Honghong Chen, Junfan Lin, Qin Wang

    306 citationsOpen access (CC-BY)doi:10.3390/molecules24234242OpenAlex

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    Nanoemulsions have attracted significant attention in food fields and can increase the functionality of the bioactive compounds contained within them. In this paper, the preparation methods, including low-energy and high-energy methods, were first reviewed. Second, the physical and chemical destabilization mechanisms of nanoemulsions, such as gravitational separation (creaming or sedimentation), flocculation, coalescence, Ostwald ripening, lipid oxidation and so on, were reviewed. Then, the impact of different stabilizers, including emulsifiers, weighting agents, texture modifiers (thickening agents and gelling agents), ripening inhibitors, antioxidants and chelating agents, on the physicochemical stability of nanoemulsions were discussed. Finally, the applications of nanoemulsions for the delivery of functional ingredients, including bioactive lipids, essential oil, flavor compounds, vitamins, phenolic compounds and carotenoids, were summarized. This review can provide some reference for the selection of preparation methods and stabilizers that will improve performance in…

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    Antimicrobial Susceptibility and Antibacterial Mechanism of Limonene against Listeria monocytogenes

    Yingjie Han, Zhichang Sun, Wenxue Chen

    304 citationsOpen access (CC-BY)doi:10.3390/molecules25010033OpenAlex

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    Limonene is a monoterpenoid compound, which is founded in a lot of plants’ essential oils with good antibacterial activity against food-borne pathogens, but it has an ambiguous antimicrobial susceptibility and mechanism against Listeria monocytogenes (L. monocytogenes). In this study, the antimicrobial susceptibility of Limonene to L. monocytogenes was studied, and some new sights regarding its antibacterial mechanism were further explored. Scanning electron microscopy (SEM) verified that limonene caused the destruction of the cell integrity and wall structure of L. monocytogenes. The increase in conductivity and the leakage of intracellular biomacromolecules (nucleic acids and proteins) confirmed that limonene had an obvious effect on cell membrane permeability. The results of Propidium Iodide (PI) fluorescence staining were consistent with the results of the conductivity measurements. This indicated that limonene treatment caused damage to the L. monocytogenes cell membrane. Furthermore, the decrease in ATP content, ATPase (Na+K+-ATPase, Ca2+-ATPase) activity and respiratory chain…

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    Deep Eutectic Solvents for Pretreatment, Extraction, and Catalysis of Biomass and Food Waste

    Payam Kalhor, Khashayar Ghandi

    303 citationsOpen access (CC-BY)doi:10.3390/molecules24224012OpenAlex

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    Valorization of lignocellulosic biomass and food residues to obtain valuable chemicals is essential to the establishment of a sustainable and biobased economy in the modern world. The latest and greenest generation of ionic liquids (ILs) are deep eutectic solvents (DESs) and natural deep eutectic solvents (NADESs); these have shown great promise for various applications and have attracted considerable attention from researchers who seek versatile solvents with pretreatment, extraction, and catalysis capabilities in biomass- and biowaste-to-bioenergy conversion processes. The present work aimed to review the use of DESs and NADESs in the valorization of biomass and biowaste as pretreatment or extraction solvents or catalysis agents.

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    Aptamers: A Review of Their Chemical Properties and Modifications for Therapeutic Application

    Tatsuo Adachi, Yoshikazu Nakamura

    299 citationsOpen access (CC-BY)doi:10.3390/molecules24234229OpenAlex

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    Aptamers are short, single-stranded oligonucleotides that bind to specific target molecules. The shape-forming feature of single-stranded oligonucleotides provides high affinity and excellent specificity toward targets. Hence, aptamers can be used as analogs of antibodies. In December 2004, the US Food and Drug Administration approved the first aptamer-based therapeutic, pegaptanib (Macugen), targeting vascular endothelial growth factor, for the treatment of age-related macular degeneration. Since then, however, no aptamer medication for public health has appeared. During these relatively silent years, many trials and improvements of aptamer therapeutics have been performed, opening multiple novel directions for the therapeutic application of aptamers. This review summarizes the basic characteristics of aptamers and the chemical modifications available for aptamer therapeutics.

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    Application of Porphyrins in Antibacterial Photodynamic Therapy

    Bamidele Amos-Tautua, Sandile P. Songca, Oluwatobi Samuel Oluwafemi

    290 citationsOpen access (CC-BY)doi:10.3390/molecules24132456OpenAlex

    Show abstract

    Antibiotics are commonly used to control, treat, or prevent bacterial infections, however bacterial resistance to all known classes of traditional antibiotics has greatly increased in the past years especially in hospitals rendering certain therapies ineffective. To limit this emerging public health problem, there is a need to develop non-incursive, non-toxic, and new antimicrobial techniques that act more effectively and quicker than the current antibiotics. One of these effective techniques is antibacterial photodynamic therapy (aPDT). This review focuses on the application of porphyrins in the photo-inactivation of bacteria. Mechanisms of bacterial resistance and some of the current 'greener' methods of synthesis of meso-phenyl porphyrins are discussed. In addition, significance and limitations of aPDT are also discussed. Furthermore, we also elaborate on the current clinical applications and the future perspectives and directions of this non-antibiotic therapeutic strategy in combating infectious diseases.

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    Chia Seeds (Salvia Hispanica L.): An Overview—Phytochemical Profile, Isolation Methods, and Application

    Maša Knez Hrnčič, Maja Ivanovski, Darija Cör, Željko Knez

    286 citationsOpen access (CC-BY)doi:10.3390/molecules25010011OpenAlex

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    L. In recent years, usage of Chia seeds has tremendously grown due to their high nutritional and medicinal values. Chia was cultivated by Mesopotamian cultures, but then disappeared for centuries until the middle of the 20th century, when it was rediscovered. Chia seeds contain healthy ω-3 fatty acids, polyunsaturated fatty acids, dietary fiber, proteins, vitamins, and some minerals. Besides this, the seeds are an excellent source of polyphenols and antioxidants, such as caffeic acid, rosmarinic acid, myricetin, quercetin, and others. Today, chia has been analyzed in different areas of research. Researches around the world have been investigating the benefits of chia seeds in the medicinal, pharmaceutical, and food industry. Chia oil is today one of the most valuable oils on the market. Different extraction methods have been used to produce the oil. In the present study, an extensive overview of the chemical composition, nutritional properties, and antioxidant and antimicrobial activities, along with extraction methods used to produce chia oil, will be discussed.

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    A Critical Review of Phenolic Compounds Extracted from the Bark of Woody Vascular Plants and Their Potential Biological Activity

    Corneliu Tanase, Sanda Coşarcă, Daniela-Lucia Muntean

    283 citationsOpen access (CC-BY)doi:10.3390/molecules24061182OpenAlex

    Show abstract

    Polyphenols are one of the largest and most widespread groups of secondary metabolites in the plants world. These compounds are of particular interest due to their occurrence and the properties they possess. The main sources of phenolic compounds are fruits and vegetables, but lately, more and more studies refer to woody vascular plants, especially to bark, as an important source of phenolic compounds with a potential biological effect. This study aims to bring together information on the phenolic compounds present in the bark of woody vascular plants by discussing extraction methods, the chemical composition of the extracts and potential biological effects. The literature data used in this paper were collected via PubMed (2004⁻2019). Search terms were: bark, rhytidome, woody vascular plant, polyphenols, phenolic compounds, biologic activity, antioxidant, immunostimulatory, antimutagenic, antibacterial, anti-inflammatory, and antitumoral. This paper intends to highlight the fact that the polyphenolic extracts obtained from the bark of woody vascular plants represent sources of…

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    Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies

    Justine Habault, Jean‐Luc Poyet

    281 citationsOpen access (CC-BY)doi:10.3390/molecules24050927OpenAlex

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    Cell-penetrating-peptides (CPPs) are small amino-acid sequences characterized by their ability to cross cellular membranes. They can transport various bioactive cargos inside cells including nucleic acids, large proteins, and other chemical compounds. Since 1988, natural and synthetic CPPs have been developed for applications ranging from fundamental to applied biology (cell imaging, gene editing, therapeutics delivery). In recent years, a great number of studies reported the potential of CPPs as carriers for the treatment of various diseases. Apart from a good efficacy due to a rapid and potent delivery, a crucial advantage of CPP-based therapies is the peptides low toxicity compared to most drug carriers. On the other hand, they are quite unstable and lack specificity. Higher specificity can be obtained using a cell-specific CPP to transport the therapeutic agent or using a non-specific CPP to transport a cargo with a targeted activity. CPP-cargo complexes can also be conjugated to another moiety that brings cell- or tissue-specificity. Studies based on all these approaches are…

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    Recent Progress of Targeted G-Quadruplex-Preferred Ligands Toward Cancer Therapy

    Sefan Asamitsu, Shunsuke Obata, Zutao Yu, Toshikazu Bando, Hiroshi Sugiyama

    277 citationsOpen access (CC-BY)doi:10.3390/molecules24030429OpenAlex

    Show abstract

    A G-quadruplex (G4) is a well-known nucleic acid secondary structure comprising guanine-rich sequences, and has profound implications for various pharmacological and biological events, including cancers. Therefore, ligands interacting with G4s have attracted great attention as potential anticancer therapies or in molecular probe applications. To date, a large variety of DNA/RNA G4 ligands have been developed by a number of laboratories. As protein-targeting drugs face similar situations, G-quadruplex-interacting drugs displayed low selectivity to the targeted G-quadruplex structure. This low selectivity could cause unexpected effects that are usually reasons to halt the drug development process. In this review, we address the recent research on synthetic G4 DNA-interacting ligands that allow targeting of selected G4s as an approach toward the discovery of highly effective anticancer drugs.

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    A Comprehensive Review on Infrared Heating Applications in Food Processing

    Salam A. Aboud, Ammar B. Altemimi, Asaad R. Al‐Hilphy, Yi-Chen Lee, Francesco Cacciola

    275 citationsOpen access (CC-BY)doi:10.3390/molecules24224125OpenAlex

    Show abstract

    Infrared (IR) technology is highly energy-efficient, less water-consuming, and environmentally friendly compared to conventional heating. Further, it is also characterized by homogeneity of heating, high heat transfer rate, low heating time, low energy consumption, improved product quality, and food safety. Infrared technology is used in many food manufacturing processes, such as drying, boiling, heating, peeling, polyphenol recovery, freeze-drying, antioxidant recovery, microbiological inhibition, sterilization grains, bread, roasting of food, manufacture of juices, and cooking food. The energy throughput is increased using a combination of microwave heating and IR heating. This combination heats food quickly and eliminates the problem of poor quality. This review provides a theoretical basis for the infrared treatment of food and the interaction of infrared technology with food ingredients. The effect of IR on physico-chemical properties, sensory properties, and nutritional values, as well as the interaction of food components under IR radiation can be discussed as a future food…

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    Ursolic Acid and Its Derivatives as Bioactive Agents

    Sithenkosi Mlala, Adebola Omowunmi Oyedeji, Mavuto Masopera Gondwe, Opeoluwa Oyehan Oyedeji

    274 citationsOpen access (CC-BY)doi:10.3390/molecules24152751OpenAlex

    Show abstract

    Non-communicable diseases (NCDs) such as cancer, diabetes, and chronic respiratory and cardiovascular diseases continue to be threatening and deadly to human kind. Resistance to and side effects of known drugs for treatment further increase the threat, while at the same time leaving scientists to search for alternative sources from nature, especially from plants. Pentacyclic triterpenoids (PT) from medicinal plants have been identified as one class of secondary metabolites that could play a critical role in the treatment and management of several NCDs. One of such PT is ursolic acid (UA, 3 β-hydroxy-urs-12-en-28-oic acid), which possesses important biological effects, including anti-inflammatory, anticancer, antidiabetic, antioxidant and antibacterial effects, but its bioavailability and solubility limits its clinical application. Mimusops caffra, Ilex paraguarieni, and Glechoma hederacea, have been reported as major sources of UA. The chemistry of UA has been studied extensively based on the literature, with modifications mostly having been made at positions C-3 (hydroxyl), C12-C13…

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    The Concept of an Ideal Antibiotic: Implications for Drug Design

    Márió Gajdács

    274 citationsOpen access (CC-BY)doi:10.3390/molecules24050892OpenAlex

    Show abstract

    The emergence and spread of antibiotic-resistant pathogens is a major public health issue, which requires global action of an intersectoral nature. Multidrug-resistant (MDR) pathogens—especially “ESKAPE” bacteria—can withstand lethal doses of antibiotics with various chemical structures and mechanisms of action. Pharmaceutical companies are increasingly turning away from participating in the development of new antibiotics, due to the regulatory environment and the financial risks. There is an urgent need for innovation in antibiotic research, as classical discovery platforms (e.g., mining soil Streptomycetes) are no longer viable options. In addition to discovery platforms, a concept of an ideal antibiotic should be postulated, to act as a blueprint for future drugs, and to aid researchers, pharmaceutical companies, and relevant stakeholders in selecting lead compounds. Based on 150 references, the aim of this review is to summarize current advances regarding the challenges of antibiotic drug discovery and the specific attributes of an ideal antibacterial drug (a prodrug or…

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    Application of Chitosan in Bone and Dental Engineering

    Alicia Aguilar, Naïmah Zein, Ezeddine Harmouch, Brahim Hafdi, Fabien Bornert and 6 more

    272 citationsOpen access (CC-BY)doi:10.3390/molecules24163009OpenAlex

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    Chitosan is a deacetylated polysaccharide from chitin, the natural biopolymer primarily found in shells of marine crustaceans and fungi cell walls. Upon deacetylation, the protonation of free amino groups of the d-glucosamine residues of chitosan turns it into a polycation, which can easily interact with DNA, proteins, lipids, or negatively charged synthetic polymers. This positive-charged characteristic of chitosan not only increases its solubility, biodegradability, and biocompatibility, but also directly contributes to the muco-adhesion, hemostasis, and antimicrobial properties of chitosan. Combined with its low-cost and economic nature, chitosan has been extensively studied and widely used in biopharmaceutical and biomedical applications for several decades. In this review, we summarize the current chitosan-based applications for bone and dental engineering. Combining chitosan-based scaffolds with other nature or synthetic polymers and biomaterials induces their mechanical properties and bioactivities, as well as promoting osteogenesis. Incorporating the bioactive molecules into…

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    Extraction, Purification, Structural Characteristics, Biological Activities and Pharmacological Applications of Acemannan, a Polysaccharide from Aloe vera: A Review

    Chang Liu, Yan Cui, Fuwei Pi, Yuliang Cheng, Yahui Guo and 1 more

    270 citationsOpen access (CC-BY)doi:10.3390/molecules24081554OpenAlex

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    Aloe vera is a medicinal plant species of the genus Aloe with a long history of usage around the world. Acemannan, considered one of the main bioactive polysaccharides of Aloe vera, possesses immunoregulation, anti-cancer, anti-oxidation, wound healing and bone proliferation promotion, neuroprotection, and intestinal health promotion activities, among others. In this review, recent advancements in the extraction, purification, structural characteristics and biological activities of acemannan from Aloe vera were summarized. Among these advancements, the structural characteristics of purified polysaccharides were reviewed in detail. Meanwhile, the biological activities of acemannan from Aloe vera determined by in vivo, in vitro and clinical experiments are summarized, and possible mechanisms of these bioactivities were discussed. Moreover, the latest research progress on the use of acemannan in dentistry and wound healing was also summarized in details. The structure-activity relationships of acemannan and its medical applications were discussed. Finally, new perspectives for future…

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    Catechin in Human Health and Disease

    Mamoru Isemura

    265 citationsOpen access (CC-BY)doi:10.3390/molecules24030528OpenAlex

    Show abstract

    Catechin, the name of which is derived from catechu of the extract of Acacia catechu L [...]

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    Red Wine Consumption and Cardiovascular Health

    Luigi Castaldo, Alfonso Narváez, Luana Izzo, Giulia Graziani, Anna Gaspari and 2 more

    264 citationsOpen access (CC-BY)doi:10.3390/molecules24193626OpenAlex

    Show abstract

    Wine is a popular alcoholic beverage that has been consumed for hundreds of years. Benefits from moderate alcohol consumption have been widely supported by the scientific literature and, in this line, red wine intake has been related to a lesser risk for coronary heart disease (CHD). Experimental studies and meta-analyses have mainly attributed this outcome to the presence in red wine of a great variety of polyphenolic compounds such as resveratrol, catechin, epicatechin, quercetin, and anthocyanin. Resveratrol is considered the most effective wine compound with respect to the prevention of CHD because of its antioxidant properties. The mechanisms responsible for its putative cardioprotective effects would include changes in lipid profiles, reduction of insulin resistance, and decrease in oxidative stress of low-density lipoprotein cholesterol (LDL-C). The aim of this review is to summarize the accumulated evidence correlating moderate red wine consumption with prevention of CHD by focusing on the different mechanisms underlying this relationship. Furthermore, the chemistry of wine…

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    Petroleum Hydrocarbon Contamination in Terrestrial Ecosystems—Fate and Microbial Responses

    Adam Truskewycz, Taylor D. Gundry, Leadin Salah Khudur, Adam Kolobaric, Mohamed Taha and 3 more

    263 citationsOpen access (CC-BY)doi:10.3390/molecules24183400OpenAlex

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    Petroleum hydrocarbons represent the most frequent environmental contaminant. The introduction of petroleum hydrocarbons into a pristine environment immediately changes the nature of that environment, resulting in reduced ecosystem functionality. Natural attenuation represents the single, most important biological process which removes petroleum hydrocarbons from the environment. It is a process where microorganisms present at the site degrade the organic contaminants without the input of external bioremediation enhancers (i.e., electron donors, electron acceptors, other microorganisms or nutrients). So successful is this natural attenuation process that in environmental biotechnology, bioremediation has developed steadily over the past 50 years based on this natural biodegradation process. Bioremediation is recognized as the most environmentally friendly remediation approach for the removal of petroleum hydrocarbons from an environment as it does not require intensive chemical, mechanical, and costly interventions. However, it is under-utilized as a commercial remediation strategy…

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    Biofilm Formation in Acinetobacter Baumannii: Genotype-Phenotype Correlation

    Cheng-Hong Yang, Pai-Wei Su, Sin‐Hua Moi, Li-Yeh Chuang

    260 citationsOpen access (CC-BY)doi:10.3390/molecules24101849OpenAlex

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    Strains of Acinetobacter baumannii are commensal and opportunistic pathogens that have emerged as problematic hospital pathogens due to its biofilm formation ability and multiple antibiotic resistances. The biofilm-associated pathogens usually exhibit dramatically decreased susceptibility to antibiotics. This study was aimed to investigate the correlation of biofilm-forming ability, antibiotic resistance and biofilm-related genes of 154 A. baumannii isolates which were collected from a teaching hospital in Taiwan. Biofilm-forming ability of the isolates was evaluated by crystal violet staining and observed by scanning electron microscopy. Antibiotic susceptibility was determined by disc diffusion method and minimum inhibitory concentration; the biofilm-related genes were screened by polymerase chain reaction. Results showed that among the 154 tested isolates, 15.6% of the clinical isolates were weak biofilm producers, while 32.5% and 45.4% of them possessed moderate and strong biofilm formation ability, respectively. The experimental results revealed that the multiple drug resistant…

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    Application of Antimicrobial Nanoparticles in Dentistry

    Wenjing Song, Shaohua Ge

    260 citationsOpen access (CC-BY)doi:10.3390/molecules24061033OpenAlex

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    Oral cavity incessantly encounters a plethora of microorganisms. Plaque biofilm-a major cause of caries, periodontitis and other dental diseases-is a complex community of bacteria or fungi that causes infection by protecting pathogenic microorganisms from external drug agents and escaping the host defense mechanisms. Antimicrobial nanoparticles are promising because of several advantages such as ultra-small sizes, large surface-area-to-mass ratio and special physical and chemical properties. To better summarize explorations of antimicrobial nanoparticles and provide directions for future studies, we present the following critical review. The keywords "nanoparticle," "anti-infective or antibacterial or antimicrobial" and "dentistry" were retrieved from Pubmed, Scopus, Embase and Web of Science databases in the last five years. A total of 172 articles met the requirements were included and discussed in this review. The results show that superior antibacterial properties of nanoparticle biomaterials bring broad prospects in the oral field. This review presents the development,…

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    Quercetin, Epigallocatechin Gallate, Curcumin, and Resveratrol: From Dietary Sources to Human MicroRNA Modulation

    Erika Cione, Chiara La Torre, Roberto Cannataro, Maria Cristina Caroleo, Pierluigi Plastina and 1 more

    251 citationsOpen access (CC-BY)doi:10.3390/molecules25010063OpenAlex

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    Epidemiologic studies suggest that dietary polyphenol intake is associated with a lower incidence of several non-communicable diseases. Although several foods contain complex mixtures of polyphenols, numerous factors can affect their content. Besides the well-known capability of these molecules to act as antioxidants, they are able to interact with cell-signaling pathways, modulating gene expression, influencing the activity of transcription factors, and modulating microRNAs. Here we deeply describe four polyphenols used as nutritional supplements: quercetin, resveratrol, epigallocatechin gallate (ECGC), and curcumin, summarizing the current knowledge about them, spanning from dietary sources to the epigenetic capabilities of these compounds on microRNA modulation.

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    Spirocyclic Motifs in Natural Products

    Evgeny Gennadievich Chupakhin, Olga Babich, Alexander Yu. Prosekov, Lyudmila Konstantinovna Asyakina, Mikhail Krasavin

    250 citationsOpen access (CC-BY)doi:10.3390/molecules24224165OpenAlex

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    Spirocyclic motifs are emerging privileged structures for drug discovery. They are also omnipresent in the natural products domain. However, until today, no attempt to analyze the structural diversity of various spirocyclic motifs occurring in natural products and their relative populations with unique compounds reported in the literature has been undertaken. This review aims to fill that void and analyze the diversity of structurally unique natural products containing spirocyclic moieties of various sizes.

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    Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer

    Bee Ling Tan, Mohd Esa Norhaizan

    246 citationsOpen access (CC-BY)doi:10.3390/molecules24142527OpenAlex

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    Many chemotherapeutic drugs have been used for the treatment of cancer, for instance, doxorubicin, irinotecan, 5-fluorouracil, cisplatin, and paclitaxel. However, the effectiveness of chemotherapy is limited in cancer therapy due to drug resistance, therapeutic selectivity, and undesirable side effects. The combination of therapies with natural compounds is likely to increase the effectiveness of drug treatment as well as reduce the adverse outcomes. Curcumin, a polyphenolic isolated from Curcuma longa, belongs to the rhizome of Zingiberaceae plants. Studies from in vitro and in vivo revealed that curcumin exerts many pharmacological activities with less toxic effects. The biological mechanisms underlying the anticancer activity of co-treatment curcumin and chemotherapy are complex and worth to discuss further. Therefore, this review aimed to address the molecular mechanisms of combined curcumin and chemotherapy in the treatment of cancer. The anticancer activity of combined nanoformulation of curcumin and chemotherapy was also discussed in this study. Taken together, a better…

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    The Preparation and Structure Analysis Methods of Natural Polysaccharides of Plants and Fungi: A Review of Recent Development

    Yan Ren, Yueping Bai, Zhidan Zhang, Wenlong Cai, Antonio Del Rio Flores

    244 citationsOpen access (CC-BY)doi:10.3390/molecules24173122OpenAlex

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    Polysaccharides are ubiquitous biomolecules found in nature that contain various biological and pharmacological activities that are employed in functional foods and therapeutic agents. Natural polysaccharides are obtained mainly by extraction and purification, which may serve as reliable procedures to enhance the quality and the yield of polysaccharide products. Moreover, structural analysis of polysaccharides proves to be promising and crucial for elucidating structure-activity relationships. Therefore, this report summarizes the recent developments and applications in extraction, separation, purification, and structural analysis of polysaccharides of plants and fungi.

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    Concepts and Core Principles of Fragment-Based Drug Design

    Philine Kirsch, Alwin M. Hartman, Anna K. H. Hirsch, Martin Empting

    243 citationsOpen access (CC-BY)doi:10.3390/molecules24234309OpenAlex

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    In this review, a general introduction to fragment-based drug design and the underlying concepts is given. General considerations and methodologies ranging from library selection/construction over biophysical screening and evaluation methods to in-depth hit qualification and subsequent optimization strategies are discussed. These principles can be generally applied to most classes of drug targets. The examples given for fragment growing, merging, and linking strategies at the end of the review are set in the fields of enzyme-inhibitor design and macromolecule-macromolecule interaction inhibition. Building upon the foundation of fragment-based drug discovery (FBDD) and its methodologies, we also highlight a few new trends in FBDD.

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    Speciation Studies of Bifunctional 3-Hydroxy-4-Pyridinone Ligands in the Presence of Zn2+ at Different Ionic Strengths and Temperatures

    Anna Irto, Paola Cardiano, Salvatore Cataldo, Karam Chand, Rosalia Maria Cigala and 7 more

    239 citationsOpen access (CC-BY)doi:10.3390/molecules24224084OpenAlex

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    The acid–base properties of two bifunctional 3-hydroxy-4-pyridinone ligands and their chelating capacity towards Zn2+, an essential bio-metal cation, were investigated in NaCl aqueous solutions by potentiometric, UV-Vis spectrophotometric, and 1H NMR spectroscopic titrations, carried out at 0.15 ≤ I/mol −1 ≤ 1.00 and 288.15 ≤ T/K ≤ 310.15. A study at I = 0.15 mol L−1 and T = 298.15 K was also performed for other three Zn2+/Lz− systems, with ligands belonging to the same family of compounds. The processing of experimental data allowed the determination of protonation and stability constants, which showed accordance with the data obtained from the different analytical techniques used, and with those reported in the literature for the same class of compounds. ESI-MS spectrometric measurements provided support for the formation of the different Zn2+/ligand species, while computational molecular simulations allowed information to be gained on the metal–ligand coordination. The dependence on ionic strength and the temperature of equilibrium constants were investigated by means of the…

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    Antibacterial Activity and Mechanisms of Essential Oil from Citrus medica L. var. sarcodactylis

    Ze-Hua Li, Ming Cai, Yuan‐Shuai Liu, Peilong Sun, Shao-Lei Luo

    239 citationsOpen access (CC-BY)doi:10.3390/molecules24081577OpenAlex

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    In this work, antibacterial activity of finger citron essential oil (FCEO, Citrus medica L. var. sarcodactylis) and its mechanism against food-borne bacteria were evaluated. A total of 28 components in the oil were identified by gas chromatography-mass spectrometry, in which limonene (45.36%), γ-terpinene (21.23%), and dodecanoic acid (7.52%) were three main components. For in vitro antibacterial tests, FCEO exhibited moderately antibacterial activity against common food-borne bacteria: Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus. It showed a better bactericidal effect on Gram-positive bacteria than Gram-negative. Mechanisms of the antibacterial action were investigated by observing changes of bacteria morphology according to scanning electron microscopy, time-kill analysis, and permeability of cell and membrane integrity. Morphology of tested bacteria was changed and damaged more seriously with increased concentration and exposure time of FCEO. FCEO showed a significant reduction effect on the growth rate of surviving bacteria and lead to lysis…

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    Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials

    Serena Silvestro, Santa Mammana, Eugenio Cavalli, Placido Bramanti, Emanuela Mazzon

    239 citationsOpen access (CC-BY)doi:10.3390/molecules24081459OpenAlex

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    . CBD is a terpenophenol and it has received a great scientific interest thanks to its medical applications. This compound showed efficacy as anti-seizure, antipsychotic, neuroprotective, antidepressant and anxiolytic. The neuroprotective activity appears linked to its excellent anti-inflammatory and antioxidant properties. The purpose of this paper is to evaluate the use of CBD, in addition to common anti-epileptic drugs, in the severe treatment-resistant epilepsy through an overview of recent literature and clinical trials aimed to study the effects of the CBD treatment in different forms of epilepsy. The results of scientific studies obtained so far the use of CBD in clinical applications could represent hope for patients who are resistant to all conventional anti-epileptic drugs.

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    Nanoparticle Delivery Systems in the Treatment of Diabetes Complications

    Eliana B. Souto, Selma B. Souto, Joana R. S. Campos, Patrícia B. Severino, Tatiana N. Pashirova and 6 more

    236 citationsOpen access (CC-BY)doi:10.3390/molecules24234209OpenAlex

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    Diabetes mellitus, an incurable metabolic disease, is characterized by changes in the homeostasis of blood sugar levels, being the subcutaneous injection of insulin the first line treatment. This administration route is however associated with limited patient's compliance, due to the risk of pain, discomfort and local infection. Nanoparticles have been proposed as insulin carriers to make possible the administration of the peptide via friendlier pathways without the need of injection, i.e., via oral or nasal routes. Nanoparticles stand for particles in the nanometer range that can be obtained from different materials (e.g., polysaccharides, synthetic polymers, lipid) and are commonly used with the aim to improve the physicochemical stability of the loaded drug and thereby its bioavailability. This review discusses the use of different types of nanoparticles (e.g., polymeric and lipid nanoparticles, liposomes, dendrimers, niosomes, micelles, nanoemulsions and also drug nanosuspensions) for improved delivery of different oral hypoglycemic agents in comparison to conventional therapies.

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    DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents

    Maria Valeria Raimondi, Ornella Randazzo, Mery La Franca, Giampaolo Barone, Elisa Vignoni and 2 more

    235 citationsOpen access (CC-BY)doi:10.3390/molecules24061140OpenAlex

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    Dihydrofolate reductase inhibitors are an important class of drugs, as evidenced by their use as antibacterial, antimalarial, antifungal, and anticancer agents. Progress in understanding the biochemical basis of mechanisms responsible for enzyme selectivity and antiproliferative effects has renewed the interest in antifolates for cancer chemotherapy and prompted the medicinal chemistry community to develop novel and selective human DHFR inhibitors, thus leading to a new generation of DHFR inhibitors. This work summarizes the mechanism of action, chemical, and anticancer profile of the DHFR inhibitors discovered in the last six years. New strategies in DHFR drug discovery are also provided, in order to thoroughly delineate the current landscape for medicinal chemists interested in furthering this study in the anticancer field.

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    Peptide-Based Drug-Delivery Systems in Biotechnological Applications: Recent Advances and Perspectives

    Diego Tesauro, Antonella Accardo, Carlo Diaferia, Vittoria Milano, Jean Guillon and 2 more

    235 citationsOpen access (CC-BY)doi:10.3390/molecules24020351OpenAlex

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    Peptides of natural and synthetic sources are compounds operating in a wide range of biological interactions. They play a key role in biotechnological applications as both therapeutic and diagnostic tools. They are easily synthesized thanks to solid-phase peptide devices where the amino acid sequence can be exactly selected at molecular levels, by tuning the basic units. Recently, peptides achieved resounding success in drug delivery and in nanomedicine smart applications. These applications are the most significant challenge of recent decades: they can selectively deliver drugs to only pathological tissues whilst saving the other districts of the body. This specific feature allows a reduction in the drug side effects and increases the drug efficacy. In this context, peptide-based aggregates present many advantages, including biocompatibility, high drug loading capacities, chemical diversity, specific targeting, and stimuli responsive drug delivery. A dual behavior is observed: on the one hand they can fulfill a structural and bioactive role. In this review, we focus on the design…

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    Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-Oncology

    Hyun Tae Lee, Sang Hyung Lee, Yong‐Seok Heo

    234 citationsOpen access (CC-BY)doi:10.3390/molecules24061190OpenAlex

    Show abstract

    Cancer cells can evade immune surveillance through the molecular interactions of immune checkpoint proteins, including programmed death 1 (PD-1), PD-L1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Since 2011, the FDA-approved antibody drugs ipilimumab (Yervoy®), nivolumab (Opdivo®), pembrolizumab (Keytruda®), cemiplimab (Libtayo®), atezolizumab (Tecentriq®), durvalumab (Imfinzi®), and avelumab (Bavencio®), which block the immune checkpoint proteins, have brought about a significant breakthrough in the treatment of a wide range of cancers, as they can induce durable therapeutic responses. In recent years, crystal structures of the antibodies against PD-1, PD-L1, and CTLA-4 have been reported. In this review, we describe the latest structural studies of these monoclonal antibodies and their interactions with the immune checkpoint proteins. A comprehensive analysis of the interactions of these immune checkpoint blockers can provide a better understanding of their therapeutic mechanisms of action. The accumulation of these structural studies would provide a basis that is…

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    PPARs as Nuclear Receptors for Nutrient and Energy Metabolism

    Fan Hong, Shijia Pan, Yuan Guo, Pengfei Xu, Yonggong Zhai

    233 citationsOpen access (CC-BY)doi:10.3390/molecules24142545OpenAlex

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    It has been more than 36 years since peroxisome proliferator-activated receptors (PPARs) were first recognized as enhancers of peroxisome proliferation. Consequently, many studies in different fields have illustrated that PPARs are nuclear receptors that participate in nutrient and energy metabolism and regulate cellular and whole-body energy homeostasis during lipid and carbohydrate metabolism, cell growth, cancer development, and so on. With increasing challenges to human health, PPARs have attracted much attention for their ability to ameliorate metabolic syndromes. In our previous studies, we found that the complex functions of PPARs may be used as future targets in obesity and atherosclerosis treatments. Here, we review three types of PPARs that play overlapping but distinct roles in nutrient and energy metabolism during different metabolic states and in different organs. Furthermore, research has emerged showing that PPARs also play many other roles in inflammation, central nervous system-related diseases, and cancer. Increasingly, drug development has been based on the use of…

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    Exogenous Melatonin Enhances Cold, Salt and Drought Stress Tolerance by Improving Antioxidant Defense in Tea Plant (Camellia sinensis (L.) O. Kuntze)

    Jiahao Li, Yiqing Yang, Kang Sun, Yi Chen, Xuan Chen and 1 more

    229 citationsOpen access (CC-BY)doi:10.3390/molecules24091826OpenAlex

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    Melatonin is a biological hormone that plays crucial roles in stress tolerance. In this study, we investigated the effect of exogenous melatonin on abiotic stress in the tea plant. Under cold, salt and drought stress, increasing malondialdehyde levels and decreasing maximum photochemical efficiency of PSII were observed in tea leaves. Meanwhile, the levels of reactive oxygen species (ROS) increased significantly under abiotic stress. Interestingly, pretreatment with melatonin on leaves alleviated ROS burst, decreased malondialdehyde levels and maintain high photosynthetic efficiency. Moreover, 100 μM melatonin-pretreated tea plants showed high levels of glutathione and ascorbic acid and increased the activities of superoxide dismutase, peroxidase, catalase and ascorbate peroxidase under abiotic stress. Notably, melatonin treatments can positively up-regulate the genes (CsSOD, CsPOD, CsCAT and CsAPX) expression of antioxidant enzyme biosynthesis. Taken together, our results confirmed that melatonin protects tea plants against abiotic stress-induced damages through detoxifying ROS and…

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    Black Chokeberry Aronia Melanocarpa L.—A Qualitative Composition, Phenolic Profile and Antioxidant Potential

    Andrzej Sidor, Anna Gramza‐Michałowska

    222 citationsOpen access (CC-BY)doi:10.3390/molecules24203710OpenAlex

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    ) is a source of many bioactive compounds with a wide spectrum of health-promoting properties. Fresh, unprocessed chokeberry fruits are rarely consumed due to their astringent taste, but they are used in the food industry for the production of juices, nectars, syrups, jams, preserves, wines, tinctures, fruit desserts, jellies, fruit teas and dietary supplements. Polyphenols are biofactors that determine the high bioactivity of chokeberries, some of the richest sources of polyphenols, which include anthocyanins, proanthocyanidins, flavonols, flavanols, proanthocyanidins, and phenolic acids. Chokeberry fruit and products have great antioxidant and health-promoting potential as they reduce the occurrence of free radicals. This publication reviewed the scientific research regarding the phenolic compounds and the antioxidant potential of chokeberry fruits, products and isolated compounds. These findings may be crucial in future research concerning chokeberry based functional food products. Chokeberry fruits can be considered as promising component of designed food with enhanced…

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    Encapsulation of Essential Oils for the Development of Biosourced Pesticides with Controlled Release: A Review

    Chloé Maes, Sandrine Bouquillon, Marie‐Laure Fauconnier

    221 citationsOpen access (CC-BY)doi:10.3390/molecules24142539OpenAlex

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    Essential oil (EO) encapsulation can be carried out via a multitude of techniques, depending on applications. Because of EOs' biological activities, the development of biosourced pesticides with EO encapsulation is of great interest. A lot of methods have been developed; they are presented in this review, together with the properties of the final products. Encapsulation conserves and protects EOs from outside aggression, but also allows for controlled release, which is useful for applications in agronomy. The focus is on the matrices that are of interest for the controlled release of their content, namely: alginate, chitosan, and cyclodextrin. Those three matrices are used with several methods in order to create EO encapsulation with different structures, capacities, and release profiles.

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    Facile Formation of Anatase/Rutile TiO2 Nanocomposites with Enhanced Photocatalytic Activity

    Jing J. He, Yi‐en Du, Yang Bai, Jing An, Xuemei Cai and 4 more

    220 citationsOpen access (CC-BY)doi:10.3390/molecules24162996OpenAlex

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    Anatase/rutile mixed-phase TiO2 nanoparticles were synthesized through a simple sol-gel route with further calcination using inexpensive titanium tetrachloride as a titanium source, which effectively reduces the production cost. The structural and optical properties of the prepared materials were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), and UV-vis adsorption. The specific surface area was also analyzed by Brunauer–Emmett–Teller (BET) method. The anatase/rutile mixed-phase TiO2 nanocomposites containing of rod-like, cuboid, and some irregularly shaped anatase nanoparticles (exposed {101} facets) with sizes ranging from tens to more than 100 nanometers, and rod-like rutile nanoparticles (exposed {110} facets) with sizes ranging from tens to more than 100 nanometers. The photocatalytic activities of the obtained anatase/rutile mixed-phase TiO2 nanoparticles were investigated and compared by evaluating the degradation of hazardous dye methylene blue (MB) under ultraviolet light illumination. Compared to the commercial Degussa P25-TiO2, the…

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    Formulation Strategies for Enhancing the Bioavailability of Silymarin: The State of the Art

    Alfonso Di Costanzo, Ruggero Angelico

    220 citationsOpen access (CC-BY)doi:10.3390/molecules24112155OpenAlex

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    ) seeds, has anti-oxidant, anti-inflammatory, anti-cancer and anti-viral activities potentially useful in the treatment of several liver disorders, such as chronic liver diseases, cirrhosis and hepatocellular carcinoma. Equally promising are the effects of silymarin in protecting the brain from the inflammatory and oxidative stress effects by which metabolic syndrome contributes to neurodegenerative diseases. However, although clinical trials have proved that silymarin is safe at high doses (>1500 mg/day) in humans, it suffers limiting factors such as low solubility in water (<50 μg/mL), low bioavailability and poor intestinal absorption. To improve its bioavailability and provide a prolonged silymarin release at the site of absorption, the use of nanotechnological strategies appears to be a promising method to potentiate the therapeutic action and promote sustained release of the active herbal extract. The purpose of this study is to review the different nanostructured systems available in literature as delivery strategies to improve the absorption and bioavailability of silymarin.

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    Cinnamomum cassia Presl: A Review of Its Traditional Uses, Phytochemistry, Pharmacology and Toxicology

    Chunling Zhang, Linhong Fan, Shunming Fan, Jiaqi Wang, Ting Luo and 3 more

    218 citationsOpen access (CC-BY)doi:10.3390/molecules24193473OpenAlex

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    Cinnamomum cassia Presl is a tropical aromatic evergreen tree of the Lauraceae family, commonly used in traditional Chinese medicine. It is also a traditional spice, widely used around the world. This paper summarizes the achievements of modern research on C. cassia, including the traditional uses, phytochemistry, pharmacology and toxicology. In addition, this review also discusses some significant issues and the potential direction of future C. cassia research. More than 160 chemicals have been separated and identified from C. cassia. The main constituents of C. cassia are terpenoids, phenylpropanoids, glycosides, etc. Modern studies have confirmed that C. cassia has a wide range of pharmacological effects, including antitumour, anti-inflammatory and analgesic, anti-diabetic and anti-obesity, antibacterial and antiviral, cardiovascular protective, cytoprotective, neuroprotective, immunoregulatory effects, anti-tyrosinase activity and other effects. However, the modern studies of C. cassia are still not complete and more in-depth investigations need to be conducted in…

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    ACPred: A Computational Tool for the Prediction and Analysis of Anticancer Peptides

    Nalini Schaduangrat, Chanin Nantasenamat, Virapong Prachayasittikul, Watshara Shoombuatong

    218 citationsOpen access (CC-BY)doi:10.3390/molecules24101973OpenAlex

    Show abstract

    Anticancer peptides (ACPs) have emerged as a new class of therapeutic agent for cancer treatment due to their lower toxicity as well as greater efficacy, selectivity and specificity when compared to conventional small molecule drugs. However, the experimental identification of ACPs still remains a time-consuming and expensive endeavor. Therefore, it is desirable to develop and improve upon existing computational models for predicting and characterizing ACPs. In this study, we present a bioinformatics tool called the ACPred, which is an interpretable tool for the prediction and characterization of the anticancer activities of peptides. ACPred was developed by utilizing powerful machine learning models (support vector machine and random forest) and various classes of peptide features. It was observed by a jackknife cross-validation test that ACPred can achieve an overall accuracy of 95.61% in identifying ACPs. In addition, analysis revealed the following distinguishing characteristics that ACPs possess: (i) hydrophobic residue enhances the cationic properties of α-helical ACPs…

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    Analysis of Cellulose and Lignocellulose Materials by Raman Spectroscopy: A Review of the Current Status

    Umesh Prasad Agarwal

    218 citationsOpen access (CC-BY)doi:10.3390/molecules24091659OpenAlex

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    This review is a summary of the Raman spectroscopy applications made over the last 10 years in the field of cellulose and lignocellulose materials. This paper functions as a status report on the kinds of information that can be generated by applying Raman spectroscopy. The information in the review is taken from the published papers and author's own research-most of which is in print. Although, at the molecular level, focus of the investigations has been on cellulose and lignin, hemicelluloses have also received some attention. The progress over the last decade in applying Raman spectroscopy is a direct consequence of the technical advances in the field of Raman spectroscopy, in particular, the application of new Raman techniques (e.g., Raman imaging and coherent anti-Stokes Raman or CARS), novel ways of spectral analysis, and quantum chemical calculations. On the basis of this analysis, it is clear that Raman spectroscopy continues to play an important role in the field of cellulose and lignocellulose research across a wide range of areas and applications, and thereby provides…

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    Allelochemicals and Signaling Chemicals in Plants

    Chui‐Hua Kong, Tran Dang Xuan, Tran Dang Khanh, Hoang-Dung Tran, Nguyễn Thành Trung

    216 citationsOpen access (CC-BY)doi:10.3390/molecules24152737OpenAlex

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    Plants abound with active ingredients. Among these natural constituents, allelochemicals and signaling chemicals that are released into the environments play important roles in regulating the interactions between plants and other organisms. Allelochemicals participate in the defense of plants against microbial attack, herbivore predation, and/or competition with other plants, most notably in allelopathy, which affects the establishment of competing plants. Allelochemicals could be leads for new pesticide discovery efforts. Signaling chemicals are involved in plant neighbor detection or pest identification, and they induce the production and release of plant defensive metabolites. Through the signaling chemicals, plants can either detect or identify competitors, herbivores, or pathogens, and respond by increasing defensive metabolites levels, providing an advantage for their own growth. The plant-organism interactions that are mediated by allelochemicals and signaling chemicals take place both aboveground and belowground. In the case of aboveground interactions, mediated air-borne…

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    Protein–Phenolic Interactions as a Factor Affecting the Physicochemical Properties of White Bean Proteins

    Łukasz Sęczyk, Michał Świeca, Ireneusz Tomasz Kapusta, Urszula Gawlik‐Dziki

    216 citationsOpen access (CC-BY)doi:10.3390/molecules24030408OpenAlex

    Show abstract

    This study was conducted with an aim to determine the interactions of pure phenolic compounds (gallic acid, ferulic acid, chlorogenic acid, quercetin, apigenin, and catechin) and phenolics from plant extracts (green tea and green coffee) with protein fractions of white bean (albumins and globulins). The physicochemical properties of complexes were established through an analysis of the UV-Vis spectrum; relative content of free amino groups, thiol groups, and tryptophan residues; chromatographic (SE-HPLC) and electrophoretic (SD-PAGE, Native-PAGE) properties; and conformational changes reflected by Fourier transform infrared spectra. Further, the effect of pH and ionic strength on the solubility and stability of complexes as well as the binding capacity of phenolics to proteins were determined. Results show that, in most cases, phenolics significantly affected the measured parameters; however, the effects were strongly differentiated by the type of phenolic compounds and protein fraction that were applied. Moreover, it may be that changes in the properties of complexes are reflected…

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    G-Quadruplex-Forming Aptamers—Characteristics, Applications, and Perspectives

    Carolina Roxo, Weronika Kotkowiak, Anna Pasternak

    210 citationsOpen access (CC-BY)doi:10.3390/molecules24203781OpenAlex

    Show abstract

    G-quadruplexes constitute a unique class of nucleic acid structures formed by G-rich oligonucleotides of DNA- or RNA-type. Depending on their chemical nature, loops length, and localization in the sequence or structure molecularity, G-quadruplexes are highly polymorphic structures showing various folding topologies. They may be formed in the human genome where they are believed to play a pivotal role in the regulation of multiple biological processes such as replication, transcription, and translation. Thus, natural G-quadruplex structures became prospective targets for disease treatment. The fast development of systematic evolution of ligands by exponential enrichment (SELEX) technologies provided a number of G-rich aptamers revealing the potential of G-quadruplex structures as a promising molecular tool targeted toward various biologically important ligands. Because of their high stability, increased cellular uptake, ease of chemical modification, minor production costs, and convenient storage, G-rich aptamers became interesting therapeutic and diagnostic alternatives to…

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    Recent Developments in Antibacterial Therapy: Focus on Stimuli-Responsive Drug-Delivery Systems and Therapeutic Nanoparticles

    Roberto Canaparo, Federica Foglietta, Francesca Giuntini, Carlo Della Pepa, Franco Dosio and 1 more

    210 citationsOpen access (CC-BY)doi:10.3390/molecules24101991OpenAlex

    Show abstract

    Conventional drugs used for antibacterial therapy display several limitations. This is not due to antibiotics being ineffective, but rather due to their low bioavailability, limited penetration to sites of infection and the rise of drug-resistant bacteria. Although new delivery systems (e.g., nanoparticles) that are loaded with antibacterial drugs have been designed to overcome these limitations, therapeutic efficacy does not seem to have improved. Against this backdrop, stimuli-responsive antibiotic-loaded nanoparticles and materials with antimicrobial properties (nanoantibiotics) present the ability to enhance therapeutic efficacy, while also reducing drug resistance and side effects. These stimuli can either be exogenous (e.g., light, ultrasound) or endogenous (e.g., pH, variation in redox gradient, enzymes). This promising therapeutic approach relies on advances in materials science and increased knowledge of microorganism growth and biofilm formation. This review provides an overview in the field of antibacterial drug-delivery systems and nanoantibiotics that benefit from a…

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    Fabrication, Flow Control, and Applications of Microfluidic Paper-Based Analytical Devices

    Hosub Lim, Ali Turab Jafry, Jinkee Lee

    208 citationsOpen access (CC-BY)doi:10.3390/molecules24162869OpenAlex

    Show abstract

    Paper-based microfluidic devices have advanced significantly in recent years as they are affordable, automated with capillary action, portable, and biodegradable diagnostic platforms for a variety of health, environmental, and food quality applications. In terms of commercialization, however, paper-based microfluidics still have to overcome significant challenges to become an authentic point-of-care testing format with the advanced capabilities of analyte purification, multiplex analysis, quantification, and detection with high sensitivity and selectivity. Moreover, fluid flow manipulation for multistep integration, which involves valving and flow velocity control, is also a critical parameter to achieve high-performance devices. Considering these limitations, the aim of this review is to (i) comprehensively analyze the fabrication techniques of microfluidic paper-based analytical devices, (ii) provide a theoretical background and various methods for fluid flow manipulation, and iii) highlight the recent detection techniques developed for various applications, including their…

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    Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System

    Kinga Fanni Tóth, Dorottya Ádám, Tamás Bı́ró, Attila Oláh

    204 citationsOpen access (CC-BY)doi:10.3390/molecules24050918OpenAlex

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    The endocannabinoid system (ECS) has lately been proven to be an important, multifaceted homeostatic regulator, which influences a wide-variety of physiological processes all over the body. Its members, the endocannabinoids (eCBs; e.g., anandamide), the eCB-responsive receptors (e.g., CB₁, CB₂), as well as the complex enzyme and transporter apparatus involved in the metabolism of the ligands were shown to be expressed in several tissues, including the skin. Although the best studied functions over the ECS are related to the central nervous system and to immune processes, experimental efforts over the last two decades have unambiguously confirmed that cutaneous cannabinoid ("c[ut]annabinoid") signaling is deeply involved in the maintenance of skin homeostasis, barrier formation and regeneration, and its dysregulation was implicated to contribute to several highly prevalent diseases and disorders, e.g., atopic dermatitis, psoriasis, scleroderma, acne, hair growth and pigmentation disorders, keratin diseases, various tumors, and itch. The current review aims to give an overview of the…

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    Ion Mobility Spectrometry in Food Analysis: Principles, Current Applications and Future Trends

    Maykel Hernández‐Mesa, David Ropartz, Ana María García-Campaña, Hélène Rogniaux, Gaud Dervilly and 1 more

    203 citationsOpen access (CC-BY)doi:10.3390/molecules24152706OpenAlex

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    In the last decade, ion mobility spectrometry (IMS) has reemerged as an analytical separation technique, especially due to the commercialization of ion mobility mass spectrometers. Its applicability has been extended beyond classical applications such as the determination of chemical warfare agents and nowadays it is widely used for the characterization of biomolecules (e.g., proteins, glycans, lipids, etc.) and, more recently, of small molecules (e.g., metabolites, xenobiotics, etc.). Following this trend, the interest in this technique is growing among researchers from different fields including food science. Several advantages are attributed to IMS when integrated in traditional liquid chromatography (LC) and gas chromatography (GC) mass spectrometry (MS) workflows: (1) it improves method selectivity by providing an additional separation dimension that allows the separation of isobaric and isomeric compounds; (2) it increases method sensitivity by isolating the compounds of interest from background noise; (3) and it provides complementary information to mass spectra and retention…

  88. 88
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    Chemical Structures and Pharmacological Profiles of Ginseng Saponins

    Zeyu Shi, Jin-Zhang Zeng, Alice S.T. Wong

    203 citationsOpen access (CC-BY)doi:10.3390/molecules24132443OpenAlex

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    that has a long history of use in traditional Chinese medicine (TCM). Among the bioactive constituents extracted from ginseng, ginseng saponins are a group of natural steroid glycosides and triterpene saponins found exclusively throughout the plant. Studies have shown that these ginseng saponins play a significant role in exerting multiple therapeutic effects. This review covers their chemical structure and classification, as well as their pharmacological activities, including their regulatory effects on immunomodulation, their anticancer effects, and their functions in the central nervous and cardiovascular systems. The general benefits of ginseng saponins for boosting physical vitality and improving quality of life are also discussed. The review concludes with fruitful directions for future research in the use of ginseng saponins as effective therapeutic agents.

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    A Comparative Review on the Extraction, Antioxidant Content and Antioxidant Potential of Different Parts of Walnut (Juglans regia L.) Fruit and Tree

    Ali Jahanban‐Esfahlan, Alireza Ostadrahimi, Mahnaz Tabibiazar, Ryszard Amarowicz

    203 citationsOpen access (CC-BY)doi:10.3390/molecules24112133OpenAlex

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    As a valuable tree nut, walnut is a well-known member of the Juglandaceae family. The fruit is made up of an outer green shell cover or husk, the middle shell which must be cracked to release the kernel, a thin layer known as skin or the seed coat, and finally, the kernel or meat. The nutritional importance of walnut fruit is ascribed to its kernel. The shell and husk are burned as fuel or discarded away as waste products. In the past two decades, the evaluation of the phenolic content and antioxidant activity of different parts of walnut has received great interest. In this contribution, the recent reports on the extraction and quantification of phenolic content from each part of the walnut tree and fruit using different solvents were highlighted and comparatively reviewed. The current review paper also tries to describe the antioxidant content of phenolic extracts obtained from different parts of the walnut tree and fruit. Additionally, the antioxidant and antiradical activities of the prepared extracts have also been discussed.

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    Review of Stimuli-Responsive Polymers in Drug Delivery and Textile Application

    Sudipta Chatterjee, Chi Leung Hui

    200 citationsOpen access (CC-BY)doi:10.3390/molecules24142547OpenAlex

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    This review describes some commercially available stimuli-responsive polymers of natural and synthetic origin, and their applications in drug delivery and textiles. The polymers of natural origin such as chitosan, cellulose, albumin, and gelatin are found to show both thermo-responsive and pH-responsive properties and these features of the biopolymers impart sensitivity to act differently under different temperatures and pH conditions. The stimuli-responsive characters of these natural polymers have been discussed in the review, and their respective applications in drug delivery and textile especially for textile-based transdermal therapy have been emphasized. Some practically important thermo-responsive polymers such as pluronic F127 (PF127) and poly(N-isopropylacrylamide) (pNIPAAm) of synthetic origin have been discussed in the review and they are of great importance commercially because of their in situ gel formation capacity. Some pH-responsive synthetic polymers have been discussed depending on their surface charge, and their drug delivery and textile applications have been…

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    A Review on the Phytochemistry, Medicinal Properties and Pharmacological Activities of 15 Selected Myanmar Medicinal Plants

    Mya Mu Aye, Hnin Thanda Aung, Myint Myint Sein, Chabaco Armijos

    199 citationsOpen access (CC-BY)doi:10.3390/molecules24020293OpenAlex

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    Medicinal plants are a reservoir of biologically active compounds with therapeutic properties that over time have been reported and used by diverse groups of people for treatment of various diseases. This review covers 15 selected medicinal plants distributed in Myanmar, including Dalbergia cultrata, Eriosema chinense, Erythrina suberosa, Millettia pendula, Sesbania grandiflora, Tadehagi triquetrum, Andrographis echioides, Barleria cristata, Justicia gendarussa, Premna integrifolia, Vitex trifolia, Acacia pennata, Cassia auriculata, Croton oblongifolius and Glycomis pentaphylla. Investigation of the phytochemical constituents, biological and pharmacological activities of the selected medicinal plants is reported. This study aims at providing a collection of publications on the species of selected medicinal plants in Myanmar along with a critical review of the literature data. As a country, Myanmar appears to be a source of traditional drugs that have not yet been scientifically investigated. This review will be support for further investigations on the pharmacological activity of…

  92. 92
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    Betanin, a Natural Food Additive: Stability, Bioavailability, Antioxidant and Preservative Ability Assessments

    Davi Vieira Teixeira da Silva, Diego dos Santos Baião, Fabrício de Oliveira Silva, Genilton Alves da Silva, Daniel Perrone and 2 more

    195 citationsOpen access (CC-BY)doi:10.3390/molecules24030458OpenAlex

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    Betanin is the only betalain approved for use in food and pharmaceutical products as a natural red colorant. However, the antioxidant power and health-promoting properties of this pigment have been disregarded, perhaps due to the difficulty in obtaining a stable chemical compound, which impairs its absorption and metabolism evaluation. Herein, betanin was purified by semi-preparative HPLC-LC/MS and identified by LC-ESI(+)-MS/MS as the pseudomolecular ion m/z 551.16. Betanin showed significant stability up to −30 °C and mild stability at chilling temperature. The stability and antioxidant ability of this compound were assessed during a human digestion simulation and ex vivo colon fermentation. Half of the betanin amount was recovered in the small intestine digestive fluid and no traces were found after colon fermentation. Betanin high antioxidant ability was retained even after simulated small intestine digestion. Betanin, besides displaying an inherent colorant capacity, was equally effective as a natural antioxidant displaying peroxy-radical scavenger ability in pork meat. Betanin…

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    Research Advances of Purple Sweet Potato Anthocyanins: Extraction, Identification, Stability, Bioactivity, Application, and Biotransformation

    Aoran Li, Ruoshi Xiao, Sijia He, Xiaoyu An, Yi He and 5 more

    193 citationsOpen access (CC-BY)doi:10.3390/molecules24213816OpenAlex

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    Purple sweet potato anthocyanins are kinds of natural anthocyanin red pigments extracted from the root or stem of purple sweet potato. They are stable and have the functions of anti-oxidation, anti-mutation, anti-tumor, liver protection, hypoglycemia, and anti-inflammation, which confer them a good application prospect. Nevertheless, there is not a comprehensive review of purple sweet potato anthocyanins so far. The extraction, structural characterization, stability, functional activity, application in the food, cosmetics, medicine, and other industries of anthocyanins from purple sweet potato, together with their biotransformation in vitro or by gut microorganism are reviewed in this paper, which provides a reference for further development and utilization of anthocyanins.

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    Porphyrin as Diagnostic and Therapeutic Agent

    Ncediwe Tsolekile, Simphiwe Maurice Nelana, Oluwatobi Samuel Oluwafemi

    193 citationsOpen access (CC-BY)doi:10.3390/molecules24142669OpenAlex

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    The synthesis and application of porphyrins has seen a huge shift towards research in porphyrin bio-molecular based systems in the past decade. The preferential localization of porphyrins in tumors, as well as their ability to generate reactive singlet oxygen and low dark toxicities has resulted in their use in therapeutic applications such as photodynamic therapy. However, their inherent lack of bio-distribution due to water insolubility has shifted research into porphyrin-nanomaterial conjugated systems to address this challenge. This has broadened their bio-applications, viz. bio-sensors, fluorescence tracking, in vivo magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT imaging to photo-immuno-therapy just to highlight a few. This paper reviews the unique theranostic role of porphyrins in disease diagnosis and therapy. The review highlights porphyrin conjugated systems and their applications. The review ends by bringing current challenges and future perspectives of porphyrin based conjugated systems and their respective applications into light.

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    Avocado Oil: Characteristics, Properties, and Applications

    Marcos Flores, Carolina Saravia, Claudia Vergara, Felipe Ávila, Hugo Valdés and 1 more

    193 citationsOpen access (CC-BY)doi:10.3390/molecules24112172OpenAlex

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    Avocado oil has generated growing interest among consumers due to its nutritional and technological characteristics, which is evidenced by an increase in the number of scientific articles that have been published on it. The purpose of the present research was to discuss the extraction methods, chemical composition, and various applications of avocado oil in the food and medicine industries. Our research was carried out through a systematic search in scientific databases. Even though there are no international regulations concerning the quality of avocado oil, some authors refer to the parameters used for olive oil, as stated by the Codex Alimentarius or the International Olive Oil Council. They indicate that the quality of avocado oil will depend on the quality and maturity of the fruit and the extraction technique in relation to temperature, solvents, and conservation. While the avocado fruit has been widely studied, there is a lack of knowledge about avocado oil and the potential health effects of consuming it. On the basis of the available data, avocado oil has established itself…

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    Click Chemistry as a Tool for Cell Engineering and Drug Delivery

    Yukiya Takayama, Kosuke Kusamori, Makiya Nishikawa

    189 citationsOpen access (CC-BY)doi:10.3390/molecules24010172OpenAlex

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    Click chemistry has great potential for use in binding between nucleic acids, lipids, proteins, and other molecules, and has been used in many research fields because of its beneficial characteristics, including high yield, high specificity, and simplicity. The recent development of copper-free and less cytotoxic click chemistry reactions has allowed for the application of click chemistry to the field of medicine. Moreover, metabolic glycoengineering allows for the direct modification of living cells with substrates for click chemistry either in vitro or in vivo. As such, click chemistry has become a powerful tool for cell transplantation and drug delivery. In this review, we describe some applications of click chemistry for cell engineering in cell transplantation and for drug delivery in the diagnosis and treatment of diseases.

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    Supercritical Fluid Extraction of Carotenoids from Vegetable Waste Matrices

    Micael de Andrade Lima, Ioannis Kestekoglou, Dimitris Charalampopoulos, Afroditi Chatzifragkou

    188 citationsOpen access (CC-BY)doi:10.3390/molecules24030466OpenAlex

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    The aim of this work was to evaluate a previously-developed model on supercritical fluid extraction (SFE) for carotenoid recovery from carrot peels on various carotenoid-rich fruit and vegetable wastes. To this end, 15 matrices, including flesh and peels of sweet potato, tomato, apricot, pumpkin and peach, as well as flesh and wastes of green, yellow and red peppers, were submitted to SFE under optimised conditions (59 °C, 350 bar, 15 g/min CO2, 15.5% (v/v) ethanol as co-solvent, 30 min of extraction time). The obtained extracts were characterised for their total carotenoid content, antioxidant activity and total carotenoid recovery (TCR). TCR values were greater than 90% w/w for most samples, with β-carotene being the most successfully extracted compound (TCRs 88–100% w/w). More polar carotenoids, such as lutein and lycopene, exhibited lower TCRs. A comparison with literature data suggested that carotenoid extraction is partially dependent on the composition of vegetable matrices, specifically on polysaccharide and moisture content. The results indicated that the optimised SFE…

  98. 98
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    Applications of Tea (Camellia sinensis) and Its Active Constituents in Cosmetics

    Wojciech Koch, Justyna Zagórska, Zbigniew Marzec, Wirginia Anna Kukula-Koch

    186 citationsOpen access (CC-BY)doi:10.3390/molecules24234277OpenAlex

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    Studies on the cosmetic applications of plant extracts are increasingly appearing in the scientific literature, which is due to the growing popularity of skincare products around the world. In the light of the observed changes, a return to natural treatment and skincare with cosmetics free of harmful substances or toxic preservatives is visible. Currently, tea extracts, due to their rich composition and various biological actions, play an important role among the dietary supplements and cosmetics. This review is intended to collect the reports on the properties of the tea plant, its extracts and preparations in cosmetology: for skin care products and for the treatment of selected dermatological diseases. Particular attention is paid to its antioxidant, anti-hyaluronidase, anti-inflammatory, slimming, hair-strengthening, photoprotective and sealing blood vessels properties.

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    Enzymes for Detoxification of Various Mycotoxins: Origins and Mechanisms of Catalytic Action

    Ilya Lyagin, Elena N. Efremenko

    185 citationsOpen access (CC-BY)doi:10.3390/molecules24132362OpenAlex

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    Mycotoxins are highly dangerous natural compounds produced by various fungi. Enzymatic transformation seems to be the most promising method for detoxification of mycotoxins. This review summarizes current information on enzymes of different classes to convert various mycotoxins. An in-depth analysis of 11 key enzyme mechanisms towards dozens of major mycotoxins was realized. Additionally, molecular docking of mycotoxins to enzymes' active centers was carried out to clarify some of these catalytic mechanisms. Analyzing protein homologues from various organisms (plants, animals, fungi, and bacteria), the prevalence and availability of natural sources of active biocatalysts with a high practical potential is discussed. The importance of multifunctional enzyme combinations for detoxification of mycotoxins is posed.

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    Curcumin and Its Derivatives as Potential Therapeutic Agents in Prostate, Colon and Breast Cancers

    Zintle Mbese, Vuyolwethu Khwaza, Blessing A. Aderibigbe

    183 citationsOpen access (CC-BY)doi:10.3390/molecules24234386OpenAlex

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    Cancer is a life-threatening disease and is the second leading cause of death around the world. The increasing threats of drug-resistant cancers indicate that there is an urgent need for the improvement or development of more effective anticancer agents. Curcumin, a phenolic compound originally derived from turmeric plant (Curcuma longa L. (Zingiberaceae family)) widely known as a spice and a coloring agent for food have been reported to possess notable anticancer activity by inhibiting the proliferation and metastasis, and enhancing cell cycle arrest or apoptosis in various cancer cells. In spite of all these benefits, the therapeutic application of curcumin in clinical medicine and its bioavailability are still limited due to its poor absorption and rapid metabolism. Structural modification of curcumin through the synthesis of curcumin-based derivatives is a potential approach to overcome the above limitations. Curcumin derivatives can overcome the disadvantages of curcumin while enhancing the overall efficacy and hindering drug resistance. This article reports a review of…

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The cohort is every article, review and book chapter OpenAlex attributes to Molecules with publication year 2019, excluding retracted works and paratext such as editorials and errata. The top 100 by citation count are listed; the percentile is the rank divided by the cohort size. 100 of the 100 entries have an abstract in OpenAlex. Counts were read on 29 October 2026 and will not be updated on this page, so a quoted rank stays verifiable. Full rules on the methodology page.

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