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Natural products (NPs) have played a significant role in modern drug discovery, serving as a source of inspiration and ideas for drug design. NPs have led to advancements in the treatment of various diseases, including infectious, cardiovascular, cancer, and multiple sclerosis. Pharmaceutical companies are shifting towards biotechnological methods to develop medicines for complex diseases. NPs offer a wider chemical space compared to synthetic compounds, with unique structural features and a diverse range of bioactive compounds. In the context of kidney disease treatment, both NPs and synthetic drugs have made significant contributions to pharmacotherapy. NPs have the potential to provide unique structural motifs for future drug development. [Extracted from the article]

The current study aimed to identify which natural products and which research directions are related to the major contributors to academic journals for diabetes therapy. Bibliometric data were extracted from the Web of Science online database using the search string TOPIC = ("natural product*' OR "natural compound*' OR "natural molecule*' OR 'phytochemical*' OR "secondary metabolite*') AND TS = ('diabet*') and analysed by a bibliometric software, VOSviewer. The search yielded 3694 publications, which were collectively cited 80,791 times, with an H-index of 117 and 21.9 citations per publication on average. The top-contributing countries were India, the USA, China, South Korea and Brazil. Curcumin, flavanone, resveratrol, carotenoid, polyphenols, flavonol, flavone and berberine were the most frequently cited natural products or compound classes. Our results provide a brief overview of the major directions of natural product research in diabetes up to now and hint on promising avenues for future research. [ABSTRACT FROM AUTHOR]

Excessive alcohol consumption is the cause of several diseases and thus is of a major concern for society. Worldwide alcohol consumption has increased by many folds over the past decades. This urgently calls for intervention and relapse counteract measures. Modern pharmacological solutions induce complete alcohol self-restraint and prevent relapse, but they have many side effects. Natural products are most promising as they cause fewer adverse effects. Here we discuss in detail the medicinal plants used in various traditional/folklore medicine systems for targeting alcohol abuse. We also comprehensively describe preclinical and clinical studies done on some of these plants along with the possible mechanisms of action. [ABSTRACT FROM AUTHOR]

Cataract is the leading reason of blindness worldwide and is defined by the presence of any lens opacities or loss of transparency. The most common symptoms of cataract are impaired vision, decreased contrast sensitivity, color disturbance, and glare. Oxidative stress is among the main mechanisms involved in the development of age-related cataract. Surgery through phacoemulsification and intraocular lens implantation is the most effective method for cataract treatment, however, there are chances of serious complications and irreversible loss of vision associated with the surgery. Natural compounds consisting of antioxidant or anti-inflammatory secondary metabolites can serve as potential leads for anticataract agents. In this review, we tried to document medicinal plants and plant-based natural products used for cataract treatment worldwide, which are gathered from available ethnopharmacological/ethnobotanical data. We have extensively explored a number of recognized databases like Scifinder, PubMed, Science Direct, Google Scholar, and Scopus by using keywords and phrases such as "cataract", "blindness", "traditional medicine", "ethnopharmacology", "ethnobotany", "herbs", "medicinal plants", or other relevant terms, and summarized the plants/phytoconstituents that are evaluated in different models of cataract and also tabulated 44 plants that are traditionally used in cataract in various folklore medical practices. Moreover, we also categorized the plants according to scientific studies carried out in different cataract models with their mechanisms of action. [ABSTRACT FROM AUTHOR]

In recent years, there has been a great deal of attention toward the molecular machinery relevant to age-related progression controlled through the external intervention of polyphenols- an epigenetic-modulating diet. Natural products modulate cellular longevity through histone post-translational modification and can also induce the upregulation of autophagy, thus reducing the level of acetyl coenzyme A (AcCoA). In addition, the effect of caloric restriction (CR) on cancer-related chronic inflammation is of great significance in aging. In line with this, SIRT1 protein levels are expanded in response to calorie restriction mimetics (CRM), in this way acting as autophagy inducers relevant to cancer prevention. [ABSTRACT FROM AUTHOR]

Background: The research into bioactive natural products of medicinal plants has a long tradition, but ethnopharmacology as a well-defined field of research has a relatively short history, only dating back 50 years. Aims: With the fast development of this field and its global importance especially in the fast developing economies of Asia it is timely to assess the most influential articles (as measured by citations) and to identify important drivers and research trends in this field. Methods: Scopus was searched to identify relevant articles which were assessed by all three authors. The 100 most cited articles were identified and analyzed. Bibliometric software (VOSviewer) was utilized to supplement the analysis and to generate a term map that visualized the citation patterns of the 100 articles containing different terms. Results: Forty-four of the 100 articles are reviews. On average, each of the 100 articles had 632 citations and since publication was cited 43 times annually. The four core journals were Journal of Ethnopharmacology (n = 17), Food Chemistry (n = 7), Life Sciences (n = 5), and Journal of Agricultural and Food Chemistry (n = 4). Anti-oxidant effects appeared to be a recurring and highly cited topic, whereas the links into drug discovery and neuropharmacology seemed to be less strong. Numerousmedicinal plants and functional foods were the foci of research, and the foci shifted when comparing pre-2000 and post-2000 publications (with the later involving a broader spectrum of plants and foods and a wider range of biological effects). Contributions largely came from Asia, and also from the Americas, Africa, and Oceania, besides Europe. Conclusion: We have identified and analyzed the 100 most-cited articles in ethnopharmacology. Within 50 years the field has gained a profile and while conventionally often linked to "traditional knowledge," drug discovery and some areas of pharmacology, this analysis highlights its emerging importance in the context of disease prevention (food science), but also the development of research driven by the needs and interests of the fast developing economies most notably of Asia. [ABSTRACT FROM AUTHOR]

Dementia is a clinical syndrome wherein gradual decline of mental and cognitive capabilities of an afflicted person takes place. Dementia is associated with various risk factors and conditions such as insufficient cerebral blood supply, toxin exposure, mitochondrial dysfunction, oxidative damage, and often coexisting with some neurodegenerative disorders such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD). Although there are well-established (semi-)synthetic drugs currently used for the management of AD and AD-associated dementia, most of them have several adverse effects. Thus, traditional medicine provides various plant-derived lead molecules that may be useful for further medical research. Herein we review the worldwide use of ethnomedicinal plants in dementia treatment. We have explored a number of recognized databases by using keywords and phrases such as "dementia", "Alzheimer's," "traditional medicine," "ethnopharmacology," "ethnobotany," "herbs," "medicinal plants" or other relevant terms, and summarized 90 medicinal plants that are traditionally used to treat dementia. Moreover, we highlight five medicinal plants or plant genera of prime importance and discuss the physiological effects, as well as the mechanism of action of their major bioactive compounds. Furthermore, the link between mitochondrial dysfunction and dementia is also discussed. We conclude that several drugs of plant origin may serve as promising therapeutics for the treatment of dementia, however, pivotal evidence for their therapeutic efficacy in advanced clinical studies is still lacking. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a cluster of three or more metabolic disorders including insulin resistance, obesity and hyperlipidemia. Obesity has become the epidemic of the twenty-first century with more than 1.6 billion overweight adults. Due to the strong connection between obesity and type 2 diabetes, obesity has received wide attention with subsequent coining of the term "diabesity". Recent studies have identified unique contributions of the immensely diverse gut microbiota in the pathogenesis of obesity and diabetes. Several mechanisms have been proposed including altered glucose and fatty acid metabolism, hepatic fatty acid storage, and modulation of glucagon-like peptide (GLP)-1. Importantly, the relationship between unhealthy diet and a modified gut microbiota composition observed in diabetic or obese subjects has been recognized. Similarly, the role of diet rich in polyphenols and plant polysaccharides in modulating gut bacteria and its impact on diabetes and obesity have been the subject of investigation by several research groups. Gut microbiota are also responsible for the extensive metabolism of polyphenols thus modulating their biological activities. The aim of this review is to shed light on the composition of gut microbes, their health importance and how they can contribute to diseases as well as their modulation by polyphenols and polysaccharides to control obesity and diabetes. In addition, the role of microbiota in improving the oral bioavailability of polyphenols and hence in shaping their antidiabetic and antiobesity activities will be discussed. [ABSTRACT FROM AUTHOR]

Natural products have always been exploited to promote health and served as a valuable source for the discovery of new drugs. In this review, the great potential of natural compounds and medicinal plants for the treatment or prevention of cardiovascular and metabolic disorders, global health problems with rising prevalence, is addressed. Special emphasis is laid on natural products for which efficacy and safety have already been proven and which are in clinical trials, as well as on plants used in traditional medicine. Potential benefits from certain dietary habits and dietary constituents, as well as common molecular targets of natural products, are also briefly discussed. A glimpse at the history of statins and biguanides, two prominent representatives of natural products (or their derivatives) in the fight against metabolic disease, is also included. The present review aims to serve as an “opening” of this special issue of Molecules, presenting key historical developments, recent advances, and future perspectives outlining the potential of natural products for prevention or therapy of cardiovascular and metabolic disease. [ABSTRACT FROM AUTHOR]

The transcription factor NF-κB is an essential mediator of inflammation; thus, the identification of compounds that interfere with the NF-κB signaling pathway is an important topic. The natural products leoligin and 5-methoxyleoligin have served as a starting point for the development of NF-κB inhibitors. Using our modular total synthesis method of leoligin, modifications at two positions were undertaken and the effects of these modifications on the biological activity were investigated. The first modification concerned the ester functionality, where it was found that variations in this position have a significant influence, with bulky esters lacking Michael-acceptor properties being favored. Additionally, the substituents on the aryl group in position 2 of the tetrahydrofuran scaffold can vary to some extent, where it was found that a 3,4-dimethoxy and a 4-fluoro substitution pattern show comparable inhibitory efficiency. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, there have been more than 10 million reported cases, more than 517,000 deaths in 215 countries, areas or territories. There is no effective antiviral medicine to prevent or treat COVID-19. Natural products and traditional medicine products with known safety profiles are a promising source for the discovery of new drug leads. There is increasing number of publications reporting the effect of natural products and traditional medicine products on COVID-19. In our review, we provide an overview of natural products and their derivatives or mimics, as well as traditional medicine products, which were reported to exhibit potential to inhibit SARS-CoV-2 infection in vitro, and to manage COVID-19 in vivo, or in clinical reports or trials. These natural products and traditional medicine products are categorized in several classes: (1) anti-malaria drugs including chloroquine and hydroxychloroquine, (2) antivirals including nucleoside analogs (remdesivir, favipiravir, β-D-N4-hydroxycytidine, ribavirin and among others), lopinavir/ritonavir and arbidol, (3) antibiotics including azithromycin, ivermectin and teicoplanin, (4) anti-protozoal drug, emetine, anti-cancer drug, homoharringtonine, and others, as well as (5) traditional medicine (Lian Hua Qing Wen Capsule, Shuang Huang Lian Oral Liquid, Qingfei Paidu Decoction and Scutellariae Radix). Randomized, double-blind and placebo-controlled large clinical trials are needed to provide solid evidence for the potential effective treatment. Currently, drug repurposing is a promising strategy to quickly find an effective treatment for COVID-19. In addition, carefully combined cocktails need to be examined for preventing a COVID-19 pandemic and the resulting global health concerns. [ABSTRACT FROM AUTHOR]

Gut microbiota metabolites have a great influence on host digestive function and body health itself. The effects of intestinal microbes on the host metabolism and nutrients absorption are mainly due to regulatory mechanisms related to serotonin, cytokines, and metabolites. Multiple studies have repeatedly reported that the gut microbiota plays a fundamental role in the absorption of bioactive compounds by converting dietary polyphenols into absorbable bioactive substances. Moreover, some intestinal metabolites derived from natural polyphenol products have more biological activities than their own fundamental biological functions. Bioactive like polyphenolic compounds, prebiotics and probiotics are the best known dietary strategies for regulating the composition of gut microbial populations or metabolic/immunological activities, which are called "three "p" for gut health". Intestinal microbial metabolites have an indirect effect on atherosclerosis, by regulating lipid metabolism and inflammation. It has been found that the diversity of intestinal microbiota negatively correlates with the development of atherosclerosis. The fewer the variation and number of microbial species in the gut, the higher the risk of developing atherosclerosis. Therefore, the atherosclerosis can be prevented and treated from the perspective of improving the number and variability of gut microbiota. In here, we summarize the effects of gut metabolites of natural products on the pathological process of the atherosclerosis, since gut intestinal metabolites not only have an indirect effect on macrophage foaming in the vessel wall, but also have a direct effect on vascular endothelial cells. [ABSTRACT FROM AUTHOR]

Holotrichia diomphalia larvae (HD), a natural product from an insect resource, possesses many pharmacological properties, including anticoagulant, antitumor, anti-inflammatory, and analgesic activity. The major bioactive ingredients include oleic acid, palmitic acid, palmitoleic acid, linoleic acid, proline, and glutamic acid. Although HD is associated with immunoregulatory activities in allergic diseases, the therapeutic mechanisms of the action of HD in allergic diseases have not been investigated. The aim of this study was to evaluate the anti-asthmatic potential of HD in an ovalbumin (OVA)-induced mouse model of allergic asthma. Moreover, the anti-inflammatory potential of HD was examined to identify a plausible mechanism of action of HD in vitro. HD strongly reduced goblet cell hyperplasia, eosinophil infiltration, and reactive oxygen species (ROS), which reduced airway hyperresponsiveness (AHR), inflammation, and the expression of Th2 cytokines (IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF). The expression of IL-5, IL-4, eotaxin-2, lysyl oxidase-like 2 (loxl2), and GATA-binding protein 3 (GATA-3) was attenuated in the lungs. In an in vitro assay, HD exerted immunomodulatory effects through the suppression of Th2 cytokines (IL-5, IL-13), IL-17, and tumor necrosis factor (TNF)-α production through downregulation of GATA-3 expression in EL-4 T cells. These findings suggest that the anti-asthmatic activity of HD may occur through the suppression of Th2 cytokines and total Immunoglobulin E (IgE) production by inhibition of the GATA-3 transcription pathway. Our results suggest that HD may be a potential alternative therapy, or a novel therapeutic traditional medicine, for the treatment of allergic asthma. [ABSTRACT FROM AUTHOR]

Many natural products have been so far tested regarding their potency to inhibit vascular smooth muscle cell proliferation, a process involved in atherosclerosis, pulmonary hypertension and restenosis. Compounds studied in vitro and in vivo as VSMC proliferation inhibitors include, for example indirubin-3′-monoxime, resveratrol, hyperoside, plumericin, pelargonidin, zerumbone and apamin. Moreover, taxol and rapamycin, the most prominent compounds applied in drug-eluting stents to counteract restenosis, are natural products. Numerous studies show that natural products have proven to yield effective inhibitors of vascular smooth muscle cell proliferation and ongoing research effort might result in the discovery of further clinically relevant compounds. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are a major cause of human death worldwide. Excessive proliferation of vascular smooth muscle cells contributes to the etiology of such diseases, including atherosclerosis, restenosis, and pulmonary hypertension. The control of vascular cell proliferation is complex and encompasses interactions of many regulatory molecules and signaling pathways. Herein, we recapitulated the importance of signaling cascades relevant for the regulation of vascular cell proliferation. Detailed understanding of the mechanism underlying this process is essential for the identification of new lead compounds (e.g., natural products) for vascular therapies. [ABSTRACT FROM AUTHOR]

The current trend of combining state of the art technologies with quondam treatments in order to overcome existing gaps in the clinical area determined an increased interest into polyphenols, common dietary phytochemicals, for the prevention and treatment of chronic diseases, especially cancer. The reemergence of polyphenols in the cancer field is sustained by advanced-omics technologies able to identify coding and non-coding genes and their related signaling pathways modulated by natural compounds. Identification of the structural correspondence between interacting molecules will allow the development of more targeted and informed therapeutic strategies for cancer management. [ABSTRACT FROM AUTHOR]

Agonists of the nuclear receptor PPARγ are therapeutically used to combat hyperglycaemia associated with the metabolic syndrome and type 2 diabetes. In spite of being effective in normalization of blood glucose levels, the currently used PPARγ agonists from the thiazolidinedione type have serious side effects, making the discovery of novel ligands highly relevant. Natural products have proven historically to be a promising pool of structures for drug discovery, and a significant research effort has recently been undertaken to explore the PPARγ-activating potential of a wide range of natural products originating from traditionally used medicinal plants or dietary sources. The majority of identified compounds are selective PPARγ modulators (SPPARMs), transactivating the expression of PPARγ-dependent reporter genes as partial agonists. Those natural PPARγ ligands have different binding modes to the receptor in comparison to the full thiazolidinedione agonists, and on some occasions activate in addition PPARα (e.g. genistein, biochanin A, sargaquinoic acid, sargahydroquinoic acid, resveratrol, amorphastilbol) or the PPARγ-dimer partner retinoid X receptor (RXR; e.g. the neolignans magnolol and honokiol). A number of in vivo studies suggest that some of the natural product activators of PPARγ (e.g. honokiol, amorfrutin 1, amorfrutin B, amorphastilbol) improve metabolic parameters in diabetic animal models, partly with reduced side effects in comparison to full thiazolidinedione agonists. The bioactivity pattern as well as the dietary use of several of the identified active compounds and plant extracts warrants future research regarding their therapeutic potential and the possibility to modulate PPARγ activation by dietary interventions or food supplements. [ABSTRACT FROM AUTHOR]

In different countries and areas of the world, traditional medicine has been and is still used for the treatment of various disorders, including chest pain or liver complaints, of which we now know that they can be linked with altered lipid and cholesterol homeostasis. As ATP-binding cassette transporter A1 (ABCA1) plays an essential role in cholesterol metabolism, its modulation may be one of the molecular mechanisms responsible for the experienced benefit of traditional recipes. Intense research activity has been dedicated to the identification of natural products from traditional medicine that regulate ABCA1 expression. This review surveys natural products, originating from ethnopharmacologically used plants, fungi or marine sources, which influence ABCA1 expression, providing a reference for future study. Information on regulation of ABCA1 expression by natural compounds from traditional medicine was extracted from ancient and modern books, materia medica, and electronic databases (PubMed, Google Scholar, Science Direct, and ResearchGate). More than 60 natural compounds from traditional medicine, especially traditional Chinese medicine (TCM), are reported to regulate ABCA1 expression in different in vitro and in vivo models (such as cholesterol efflux and atherosclerotic animal models). These active compounds belong to the classes of polyketides, terpenoids, phenylpropanoids, tannins, alkaloids, steroids, amino acids and others. Several compounds appear very promising in vivo , which need to be further investigated in animal models of diseases related to ABCA1 or in clinical studies. Natural products from traditional medicine constitute a large promising pool for compounds that regulate ABCA1 expression, and thus may prevent/treat diseases related to cholesterol metabolism, like atherosclerosis or Alzheimer's disease. In many cases, the molecular mechanisms of these natural products remain to be investigated. Image 1 [ABSTRACT FROM AUTHOR]