Flavonoids: structure–function and mechanisms of action and opportunities for drug development

Safe, Stephen; Jayaraman, Arul; Chapkin, Robert S.; Howard, Marcell; Mohankumar, Kumaravel; Shrestha, Rupesh

doi:10.1007/s43188-020-00080-z

Cited by 76 publications

(65 citation statements)

References 186 publications

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“…The leaf is the most commonly used plant part for therapeutic purposes and its main phytochemicals include glucosides (glucosinolates), phenolics (phenolic acids and flavonoids), and carotenoids (β-carotene) [18,29,65,66]. The structures of different classes of major phytochemicals present in the MO leave extracts are shown in Figure 8 [67,68]. Glucosinolates are bioactive after being hydrolyzed by the endogenous enzyme myrosinase to thiocyanates, isothiocyanates, and nitriles, which are the active molecules with hypoglycemic effects [49,69,70].…”

Section: Pharmacological Properties Of Mo Extractsmentioning

confidence: 99%

Moringa oleifera Lam. in Diabetes Mellitus: A Systematic Review and Meta-Analysis

et al. 2021

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Plant-derived phytochemicals have been interested in as nutraceuticals for preventing the onset and progress of diabetes mellitus and its serious complications in recent years. Moringa oleifera Lam. is used in vegetables and in herbal medicine for its health-promoting properties against various diseases including diabetes mellitus. This study aimed to examine an effect of Moringa oleifera on diabetic hyperglycemia and dyslipidemia by meta-analyzing the current evidence of diabetic rodent models. Peer-reviewed studies written in English from two databases, PubMed and Embase, were searched to 30 April 2021. Studies reporting blood glucose or lipid levels in diabetic rodents with and without receiving extracts of Moringa oleifera were included. Forty-four studies enrolling 349 diabetic rodents treated with extracts of Moringa oleifera and 350 diabetic controls reported blood glucose levels. The pooled effect size was −3.92 (95% CI: −4.65 to −3.19) with a substantial heterogeneity. This effect was likely to be, at least in part, modified by the type of diabetic models. Moreover, diabetic hypertriglyceridemia and hypercholesterolemia were also significantly improved in diabetic rodent models treated with Moringa oleifera.

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Section: Pharmacological Properties Of Mo Extractsmentioning

confidence: 99%

Moringa oleifera Lam. in Diabetes Mellitus: A Systematic Review and Meta-Analysis

et al. 2021

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“…However, most dietary flavonoids exhibit antioxidant activities and they also enhance the immune system. These effects coupled with other individual flavonoid-dependent responses contribute to their chemoprevention of diseases [ 12 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

Flavonoids kaempferol and quercetin are nuclear receptor 4A1 (NR4A1, Nur77) ligands and inhibit rhabdomyosarcoma cell and tumor growth

Shrestha

Mohankumar

Martin

et al. 2021

J Exp Clin Cancer Res

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Background Flavonoids exhibit both chemopreventive and chemotherapeutic activity for multiple tumor types, however, their mechanisms of action are not well defined. Based on some of their functional and gene modifying activities as anticancer agents, we hypothesized that kaempferol and quercetin were nuclear receptor 4A1 (NR4A1, Nur77) ligands and confirmed that both compounds directly bound NR4A1 with KD values of 3.1 and 0.93 μM, respectively. Methods The activities of kaempferol and quercetin were determined in direct binding to NR4A1 protein and in NR4A1-dependent transactivation assays in Rh30 and Rh41 rhabdomyosarcoma (RMS) cells. Flavonoid-dependent effects as inhibitors of cell growth, survival and invasion were determined in XTT and Boyden chamber assays respectively and changes in protein levels were determined by western blots. Tumor growth inhibition studies were carried out in athymic nude mice bearing Rh30 cells as xenografts. Results Kaempferol and quercetin bind NR4A1 protein and inhibit NR4A1-dependent transactivation in RMS cells. NR4A1 also regulates RMS cell growth, survival, mTOR signaling and invasion. The pro-oncogenic PAX3-FOXO1 and G9a genes are also regulated by NR4A1 and, these pathways and genes are all inhibited by kaempferol and quercetin. Moreover, at a dose of 50 mg/kg/d kaempferol and quercetin inhibited tumor growth in an athymic nude mouse xenograft model bearing Rh30 cells. Conclusion These results demonstrate the clinical potential for repurposing kaempferol and quercetin for clinical applications as precision medicine for treating RMS patients that express NR4A1 in order to increase the efficacy and decrease dosages of currently used cytotoxic drugs.

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“…These backbones occur in various modified forms through hydroxylation, methylation, and glycosylation by transferases. Occasionally other decorations may attach to the aglycones such as sulphates and aliphatic acids [34][35][36]. In the current study, flavonoids identified had aglycones that fall into 4 subclasses which mostly were flavonols (quercetin, kaempferol and isorhamnetin), two anthocyanins (cyanidin and delphinidin), one flavanone, one flavone and one aurone flavonoid (maritimetin, structural isomers of flavones) as listed in Table S1 and Figure 1, decorated with various sugar attachments.…”

Section: Major Chemical Classes Of Momordica Metabolomesmentioning

confidence: 62%

Metabolomics and Molecular Networking to Characterize the Chemical Space of Four Momordica Plant Species

et al. 2021

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Momordica plant species (Cucurbitaceae), have been used for centuries in traditional medicine and for nutritional purposes. Plants from this family are thus claimed to be phytochemically rich, representing an inexhaustible source of natural products. However, the chemical space of these Momordica species has not yet been fully decoded, and due to the inherent complexity of plant metabolomes, the characterization of the Momordica phytochemistry remains challenging. Thus, in this study we propose the use of molecular networking to unravel the molecular families within the metabolomes of four Momordica species (M. cardiospermoides, M. balsamina, M. charantia and M. foetida) and highlight the relevance of molecular networking in exploring the chemotaxonomy of these plants. In silico annotation tools (Network Annotation Propagation and DEREPLICATOR) and an unsupervised substructure identification tool (MS2LDA) were also explored to complement the classical molecular networking output and integration using MolNetEnhancer within GNPS. This allowed for the visualisation of chemical classes and the variety of substructures within the molecular families. The use of computational tools in this study highlighted various classes of metabolites, such as a wide range of flavonoids, terpenoids and lipids. Herein, these species are revealed to be phytochemically rich plants consisting of many biologically active metabolites differentially distributed within the different species, with the metabolome of M. cardiospermoides dereplicated in this paper for the first time.

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Flavonoids: structure–function and mechanisms of action and opportunities for drug development

Cited by 76 publications

References 186 publications

Moringa oleifera Lam. in Diabetes Mellitus: A Systematic Review and Meta-Analysis

Moringa oleifera Lam. in Diabetes Mellitus: A Systematic Review and Meta-Analysis

Flavonoids kaempferol and quercetin are nuclear receptor 4A1 (NR4A1, Nur77) ligands and inhibit rhabdomyosarcoma cell and tumor growth

Metabolomics and Molecular Networking to Characterize the Chemical Space of Four Momordica Plant Species

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