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1.
Flavanols from Nature: A Phytochemistry and Biological Activity Review.
Luo, Y, Jian, Y, Liu, Y, Jiang, S, Muhammad, D, Wang, W
Molecules (Basel, Switzerland). 2022;(3)
Abstract
Flavanols, a common class of secondary plant metabolites, exhibit several beneficial health properties by acting as antioxidant, anticarcinogen, cardioprotective, anti-microbial, anti-viral, and neuroprotective agents. Furthermore, some flavanols are considered functional ingredients in dairy products. Based on their structural features and health-promoting functions, flavanols have gained the attention of pharmacologists and botanists worldwide. This review collects and summarizes 121 flavanols comprising four categories: flavan-3-ols, flavan-4-ols, isoflavan-4-ols, and flavan-3,4-ols. The research of the various structural features and pharmacological activities of flavanols and their derivatives aims to lay the groundwork for subsequent research and expect to provide mentality and inspiration for the research. The current study provides a starting point for further research and development.
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An In Silico and an In Vitro Inhibition Analysis of Glycogen Phosphorylase by Flavonoids, Styrylchromones, and Pyrazoles.
Rocha, S, Aniceto, N, Guedes, RC, Albuquerque, HMT, Silva, VLM, Silva, AMS, Corvo, ML, Fernandes, E, Freitas, M
Nutrients. 2022;(2)
Abstract
Glycogen phosphorylase (GP) is a key enzyme in the glycogenolysis pathway. GP inhibitors are currently under investigation as a new liver-targeted approach to managing type 2 diabetes mellitus (DM). The aim of the present study was to evaluate the inhibitory activity of a panel of 52 structurally related chromone derivatives; namely, flavonoids, 2-styrylchromones, 2-styrylchromone-related derivatives [2-(4-arylbuta-1,3-dien-1-yl)chromones], and 4- and 5-styrylpyrazoles against GP, using in silico and in vitro microanalysis screening systems. Several of the tested compounds showed a potent inhibitory effect. The structure-activity relationship study indicated that for 2-styrylchromones and 2-styrylchromone-related derivatives, the hydroxylations at the A and B rings, and in the flavonoid family, as well as the hydroxylation of the A ring, were determinants for the inhibitory activity. To support the in vitro experimental findings, molecular docking studies were performed, revealing clear hydrogen bonding patterns that favored the inhibitory effects of flavonoids, 2-styrylchromones, and 2-styrylchromone-related derivatives. Interestingly, the potency of the most active compounds increased almost four-fold when the concentration of glucose increased, presenting an IC50 < 10 µM. This effect may reduce the risk of hypoglycemia, a commonly reported side effect of antidiabetic agents. This work contributes with important considerations and provides a better understanding of potential scaffolds for the study of novel GP inhibitors.
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3.
Antiproliferative and palliative activity of flavonoids in colorectal cancer.
Fernández, J, Silván, B, Entrialgo-Cadierno, R, Villar, CJ, Capasso, R, Uranga, JA, Lombó, F, Abalo, R
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021;:112241
Abstract
Flavonoids are plant bioactive compounds of great interest in nutrition and pharmacology, due to their remarkable properties as antioxidant, anti-inflammatory, antibacterial, antifungal and antitumor drugs. More than 5000 different flavonoids exist in nature, with a huge structural diversity and a plethora of interesting pharmacological properties. In this work, five flavonoids were tested for their potential use as antitumor drugs against three CRC cell lines (HCT116, HT-29 and T84). These cell lines represent three different stages of this tumor, one of which is metastatic. Xanthohumol showed the best antitumor activity on the three cancer cell lines, even better than that of the clinical drug 5-fluorouracil (5-FU), although no synergistic effect was observed in the combination therapy with this drug. On the other hand, apigenin and luteolin displayed slightly lower antitumor activities on these cancer cell lines but showed a synergistic effect in combination with 5-FU in the case of HTC116, which is of potential clinical interest. Furthermore, a literature review highlighted that these flavonoids show very interesting palliative effects on clinical symptoms such as diarrhea, mucositis, neuropathic pain and others often associated with the chemotherapy treatment of CRC. Flavonoids could provide a double effect for the combination treatment, potentiating the antitumor effect of 5-FU, and simultaneously, preventing important side effects of 5-FU chemotherapy.
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Oral Pycnogenol® Intake Benefits the Skin in Urban Chinese Outdoor Workers: A Randomized, Placebo-Controlled, Double-Blind, and Crossover Intervention Study.
Zhao, H, Wu, J, Wang, N, Grether-Beck, S, Krutmann, J, Wei, L
Skin pharmacology and physiology. 2021;(3):135-145
Abstract
BACKGROUND Oral supplementation with a standardized extract from the bark of the French pine (Pycnogenol®) has been reported to benefit the skin. It might thus represent an easy-to-use strategy to improve the skin health of individuals who are exposed to considerable environmental stress in large urban areas. OBJECTIVE We investigated if oral intake of Pycnogenol® can benefit the skin of Han Chinese working outdoors in Beijing, China. METHODS In a monocentre, double-blind, randomized, placebo-controlled, and crossover study, the effects of Pycnogenol® intake (2 × 50 mg/day for a total of 12 weeks) on a variety of skin physiological parameters was studied in Chinese subjects (n = 76), from spring to autumn, who were working outdoors in Beijing, China. RESULTS During the intervention period, study subjects were constantly exposed to increased levels of particulate matter (PM)2.5 as well as seasonal changes in humidity and temperature. Despite this environmental stress, Pycnogenol® intake prevented (i) a decrease in the skin hydration, (ii) transepidermal water loss (TEWL), and (iii) skin darkening during the dry autumn season. In addition, Pycnogenol® intake improved (iv) viscoelastic skin properties such as gross elasticity and elastic recovery irrespective of the season. These beneficial effects were not observed if the same subjects were supplemented with placebo. CONCLUSION Oral intake of Pycnogenol® benefits the skin in Han Chinese, who are working outdoors under considerable environmental stress.
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Flavonoids as potential phytotherapeutics to combat cytokine storm in SARS-CoV-2.
Gour, A, Manhas, D, Bag, S, Gorain, B, Nandi, U
Phytotherapy research : PTR. 2021;(8):4258-4283
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Abstract
Emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, COVID-19, has become the global panic since December 2019, which urges the global healthcare professionals to identify novel therapeutics to counteract this pandemic. So far, there is no approved treatment available to control this public health issue; however, a few antiviral agents and repurposed drugs support the patients under medical supervision by compromising their adverse effects, especially in emergency conditions. Only a few vaccines have been approved to date. In this context, several plant natural products-based research studies are evidenced to play a crucial role in immunomodulation that can prevent the chances of infection as well as combat the cytokine release storm (CRS) generated during COVID-19 infection. In this present review, we have focused on flavonoids, especially epicatechin, epigallocatechin gallate, hesperidin, naringenin, quercetin, rutin, luteolin, baicalin, diosmin, ge nistein, biochanin A, and silymarin, which can counteract the virus-mediated elevated levels of inflammatory cytokines leading to multiple organ failure. In addition, a comprehensive discussion on available in silico, in vitro, and in vivo findings with critical analysis has also been evaluated, which might pave the way for further development of phytotherapeutics to identify the potential lead candidatetoward effective and safe management of the SARS-CoV-2 disease.
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Comparative Metabolic Profiling in Pulp and Peel of Green and Red Pitayas (Hylocereus polyrhizus and Hylocereus undatus) Reveals Potential Valorization in the Pharmaceutical and Food Industries.
Lin, X, Gao, H, Ding, Z, Zhan, R, Zhou, Z, Ming, J
BioMed research international. 2021;:6546170
Abstract
Pitaya (Hylocereus genus) is a popular plant with exotic and nutritious fruit, which has widespread uses as a source of nutrients and raw materials in the pharmaceutical industry. However, the potential of pitaya peel as a natural source of bioactive compounds has not yet fully been explored. Recent advances in metabolomics have paved the way for understanding and evaluating the presence of diverse sets of metabolites in different plant parts. This study is aimed at exploring the diversity of primary and secondary metabolites in two commercial varieties of pitaya, i.e., green pitaya (Hylocereus undatus) and red pitaya (Hylocereus polyrhizus). A total of 433 metabolites were identified using a widely targeted metabolomic approach and classified into nine known diverse classes of metabolites, including flavonoids, amino acids and its derivatives, alkaloids, tannins, phenolic acids, organic acids, nucleotides and derivatives, lipids, and lignans. Red pitaya peel and pulp showed relatively high accumulation of metabolites viz. alkaloids, amino acids and its derivatives, and lipids. Differential metabolite landscape of pitaya fruit indicated the presence of key bioactive compounds, i.e., L-tyrosine, L-valine, DL-norvaline, tryptophan, γ-linolenic acid, and isorhamnetin 3-O-neohesperidoside. The findings in this study provide new insight into the broad spectrum of bioactive compounds of red and green pitaya, emphasizing the valorization of the biowaste pitaya peel as raw material for the pharmaceutical and food industries.
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Flavonoids Seen through the Energy Perspective.
Li, Z, Zhang, M, Haenen, GRMM, Vervoort, L, Moalin, M
International journal of molecular sciences. 2021;(1)
Abstract
In all life forms, opposing forces provide the energy that flows through networks in an organism, which fuels life. In this concept, health is the ability of an organism to maintain the balance between these opposing forces, which creates resilience, and a deranged flow of energy is the basis for diseases. Treatment should focus on adjusting the deranged flow of energy, e.g., by the redox modulating activity of antioxidants. A major group of antioxidants is formed by flavonoids, a group of polyphenolic compounds abundantly present in our diet. The objective here is to review how the redox modulation by flavonoids fits in the various concepts on the mode of action of bioactive compounds, so we can 'see' where there is overlap and where the missing links are. Based on this fundament, we should choose our research path aiming to 'understand' the redox modulating profile of specific flavonoids, so we can ultimately rationally apply the redox modulating power of flavonoids to improve our health.
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Baicalein, Baicalin, and Wogonin: Protective Effects against Ischemia-Induced Neurodegeneration in the Brain and Retina.
Pan, L, Cho, KS, Yi, I, To, CH, Chen, DF, Do, CW
Oxidative medicine and cellular longevity. 2021;:8377362
Abstract
Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).
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Effects of 12 Weeks Cosmos caudatus Supplement among Older Adults with Mild Cognitive Impairment: A Randomized, Double-Blind and Placebo-Controlled Trial.
You, YX, Shahar, S, Rajab, NF, Haron, H, Yahya, HM, Mohamad, M, Din, NC, Maskat, MY
Nutrients. 2021;(2)
Abstract
Cosmos caudatus (CC) contains high flavonoids and might be beneficial in neuroprotection. It has the potential to prevent neurodegenerative diseases. Therefore, we aimed to investigate the effects of 12 weeks of Cosmos caudatus supplement on cognitive function, mood status, blood biochemical profiles and biomarkers among older adults with mild cognitive impairment (MCI) through a double-blind, placebo-controlled trial. The subjects were randomized into CC supplement (n = 24) and placebo group (n = 24). Each of them consumed one capsule of CC supplement (250 mg of CC/capsule) or placebo (500 mg maltodextrin/capsule) twice daily for 12 weeks. Cognitive function and mood status were assessed at baseline, 6th week, and 12th week using validated neuropsychological tests. Blood biochemical profiles and biomarkers were measured at baseline and 12th week. Two-way mixed analysis of variance (ANOVA) analysis showed significant improvements in mini mental state examination (MMSE) (partial η2 = 0.150, p = 0.049), tension (partial η2 = 0.191, p = 0.018), total mood disturbance (partial η2 = 0.171, p = 0.028) and malondialdehyde (MDA) (partial η2 = 0.097, p = 0.047) following CC supplementation. In conclusion, 12 weeks CC supplementation potentially improved global cognition, tension, total mood disturbance, and oxidative stress among older adults with MCI. Larger sample size and longer period of intervention with incorporation of metabolomic approach should be conducted to further investigate the underlying mechanism of CC supplementation in neuroprotection.
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Tea intake and cardiovascular disease: an umbrella review.
Keller, A, Wallace, TC
Annals of medicine. 2021;(1):929-944
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Abstract
Brewed tea (Camellia sinensis) is a major dietary source of flavonoids, in particular flavan-3-ols. Tea consumption has been suggested to be inversely associated with a decreased risk of cardiovascular disease (CVD). Several biological mechanisms support the inverse relationship between tea flavonoid intake and CVD risk. Given the recent accumulating evidence from various systematic reviews regarding the role of tea as a beverage in reducing CVD risk and severity, we conducted an umbrella review to describe and critically evaluate the totality of evidence to date. We searched the PubMed, Web of Science, Cochrane Database of Systematic Reviews, and BIOSIS databases for systematic reviews published between January 1, 2010 and February 22, 2020 reporting relationships between tea (C. sinensis) consumption and CVD mortality, CVD diagnosis or incidence, CVD events, stroke events, blood pressure, endothelial function, blood lipids and triglycerides, and inflammatory markers. Herein, we describe results from 23 included systematic reviews. Consistently consuming 2 cups of unsweet tea per day offers the right levels of flavonoids to potentially decrease CVD risk and its progression. This is supported by the consistency between a recent high-quality systematic review and dose-response meta-analyses of population-based studies demonstrating beneficial effects of consumption on CVD mortality, CVD events and stroke events and medium- to high-quality systematic reviews of intervention studies that further elucidate potential benefits on both validated (i.e., SBP, DBP, total cholesterol, and LDL-cholesterol) and emerging risk biomarkers of CVD (TNF-ɑ and IL-6). On the basis of this umbrella review, the consumption of tea as a beverage did not seem to be harmful to health; therefore, the benefits of moderate consumption likely outweigh risk. Future large, clinical intervention studies will provide better mechanistic insight with the ability to confirm the outcome effects shown across observational studies. The review protocol was registered on PROSPERO (https://www.crd.york.ac.uk/PROSPERO/) as CRD42020218159.KEY MESSAGESIt is reasonable to judge that 2 cups of unsweet tea per day has the potential to decrease CVD risk and progression due to its flavonoid content.The primary side effects of tea documented in human studies are hepatotoxicity and gastrointestinal disturbances (i.e., vomiting and diarrhea) after high-dose supplemental intake.Additional clinical research is needed to fully elucidate the effects of tea flavonoids on markers of CVD, as many studies were under-powered to detect changes.[Figure: see text].