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Effects of myricetin on glucose tolerance after a single-dose injection. Wistar rats were administered liraglutide or myricetin after a period of food withdrawal. Glucose (2 g/kg body weight) was administered 30 min before each time point (0–48 h). A) The effect of a single dose of the myricetin (250 mg/kg body weight by oral) and liraglutide (100 mg/kg body weight) on glucose regulation in Wistar rats. B) The dosage-efficacy of myricetin 12 h after administration. The administration of myricetin maintained the blood glucose concentration at normal levels for 8 h after a single-dose treatment, suggesting it might possess a half-life similar to that of liraglutide (11.3 h).
Source publication
The physiologic properties of glucagon-like peptide 1 (GLP-1) make it a potent candidate drug target in the treatment of type 2 diabetes mellitus (T2DM). GLP-1 is capable of regulating the blood glucose level by insulin secretion after administration of oral glucose. The advantages of GLP-1 for the avoidance of hypoglycemia and the control of body...
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Introduction
Glucagon-like peptide-1 (GLP-1) increases insulin secretion from pancreatic beta-cells and GLP-1 receptor (GLP-1R) agonists are widely used as treatment for type 2 diabetes mellitus. Studying occupancy of the GLP-1R in various tissues is challenging due to lack of quantitative, repeatable assessments of GLP-1R density. The present stud...
Gastrointestinal hormones are currently used to treat type 2 diabetes mellitus (T2D). Incretin preparations with gastric inhibitory polypeptide (GIP) activity or glucagon-like peptide-1 (GLP-1) provide new means for controlling blood glucose levels, body weight, and lipid metabolism. GIP, an incretin, has not been used due to lack of promising acti...
Type 2 diabetes mellitus (T2DM) has become one of the leading causes of morbidity and mortality in developed countries. Low efficacy, weight gain, and hypoglycemia are the main pitfalls of previous treatments for T2DM. New therapies have been designed with the aim of improving the results in efficacy and quality of life. Glucagon-like peptide 1 (GL...
Citations
... Wistar rats revealed its' glucoregulatory activity. 44 Li et al 45 have proved Myricetin as an active anticancer compound with pharmacological effects on tamoxifen and its metabolites. Rosmarinic acid pharmacokinetic properties are a good recommendation for oral prescription as it has a low acute toxicity value. ...
... The derivatives of flavonoid have been proven to have a similar effect to DPP-4 inhibitor agent (7). Another research found ten substrates from flavonoid which showed similar effect to DPP4 inhibitor agent such as hibiscetin, gossypentin, gossypetin -3-glucoside, myricetin, myricetin 3-glucoside, alpha spinasterol, quercetin, syringaresinol, stigmasterol, and isoquercetin (8)(9)(10). This study aimed to prove the effect of oral Gedi leaves extract in increase GLP-1 serum and decrease Fasting Blood Glucose (FBG) level compared to DPP-4 inhibitor in hyperglycemia male rat. ...
... In contrast, myricetin showed least interaction with PPAR-γ, indicating that its role in modulating PPAR-γ activity may be limited suggesting alternate mechanisms of glucose homeostasis. Some studies have suggested that myricetin administration might be beneficial for increasing insulin sensitivity and inhibiting islet β-cell apoptosis by acting as Glucagon-like peptide-1 (GLP-1) agonist [11] . ...
Diabetes mellitus remains to be a significant global metabolic disorder, affecting both human and animal populations. Plant-derived medications have gained focus for diabetes management due to their perceived safety compared to conventional drugs. Recent research has emphasized the potential of polyphenols, particularly flavonols, in modulating genes related to insulin secretion and signalings pathways, indicating their potential role in preventing type II diabetes. This study investigates the interactions of three plant flavonols—quercetin, kaempferol, and myricetin—with two critical proteins involved in glucose homeostasis: PPAR-γ and GLUT-4 through in-silico docking analysis performed using Biovia Discovery Studio (version 2020). Our docking results revealed that kaempferol showed significant binding affinity for PPAR-γ, with a LibDock score of 95.462, interacting notably with residues THR269 and ASP271. Quercetin demonstrated moderate binding affinity (LibDock score of 46.657), while myricetin exhibited no interactions with PPAR-γ. For GLUT-4, myricetin had the highest docking score of 98.347, indicating strong binding affinity, with favorable interactions at residues SER412, LEU410, SER480, and LYS266. Quercetin also interacted with GLUT-4 (LibDock score: 95.317), binding to residues SER412, LYS266, and LEU410. Kaempferol with a dock score of 92.997 interacted with HIS484 and LYS266. The common interaction of amino acid residue LYS266 with all flavonols underscores its role in mediating their effects. The findings thus highlight the potential of flavonols in influencing glucose homeostasis through interactions with key proteins. Further pharmacokinetic studies and in vitro and in vivo validations are necessary to establish their efficacy and safety as anti-diabetic agents.
... The flavonoid myricetin is prevalent in various teas, plants, and fruits [97]. Recent discoveries have unveiled the mechanisms of action of myricetin in diabetes, such as DPP4 inhibition [98], GLP-1 inactivation, or acting as a GLP-1 receptor agonist [99]. Notably, myricetin appears to normalize gut flora in T2D-afflicted mice [100]. ...
There are a wide variety of phytochemicals collectively known as polyphenols. Their structural diversity results in a broad range of characteristics and biological effects. Polyphenols can be found in a variety of foods and drinks, including fruits, cereals, tea, and coffee. Studies both in vitro and in vivo, as well as clinical trials, have shown that they possess potent antioxidant activities, numerous therapeutic effects, and health advantages. Dietary polyphenols have demonstrated the potential to prevent many health problems, including obesity, atherosclerosis, high blood sugar, diabetes, hypertension, cancer, and neurological diseases. In this paper, the protective effects of polyphenols and the mechanisms behind them are investigated in detail, citing the most recent available literature. This review aims to provide a comprehensive overview of the current knowledge on the role of polyphenols in preventing and managing chronic diseases. The cited publications are derived from in vitro, in vivo, and human-based studies and clinical trials. A more complete understanding of these naturally occurring metabolites will pave the way for the development of novel polyphenol-rich diet and drug development programs. This, in turn, provides further evidence of their health benefits.
... Conversely, several natural substances also directly stimulate the GLP-1 receptors. These substances include Geniposide [14], Catalpol [15], Puerarin [16], Myricetin [17], Morroniside [18], and Cinchonine [19]. ...
The phenolic aldehyde syringaldehyde (SA) has been shown to have an antihyperglycemic effect in diabetic rats due to increased glucose utilization and insulin sensitivity. To understand the direct effect of SA on the GLP-1 receptor, STZ-induced diabetic rats were used. The levels of pro-inflammatory cytokines, liver enzymes, and renal function were measured using specific ELISA kits. The mechanisms of SA effects were investigated using CHO-K1 cells, pancreatic Min-6 cells, and cardiomyocyte H9c2 cells. The results indicated that the antihyperglycemic effect of SA in diabetic rats was abolished by blocking the GLP-1 receptor with an antagonist. SA has a direct effect on the GLP-1 receptor when using CHO-K1 cells transfected with the exogenous GLP-1 receptor gene. In addition, SA stimulated insulin production in Min-6 cells by activating GLP-1 receptors. SA caused a dose-dependent rise in GLP-1 receptor mRNA levels in cardiac H9c2 cells. These in vitro results support the notion that SA has a direct effect on the GLP-1 receptor. Otherwise, SA inhibited the increase of pro-inflammatory cytokines, including interleukins and tumor TNF-α, in type 1 diabetic rats in a dose-dependent manner. Moreover, as with liraglutide, SA reduced plasma lipid profiles, including total cholesterol and triglyceride, in mixed diet-induced type 2 diabetic rats. Intriguingly, chronic treatment with SA (as with liraglutide) reversed the functions of both the liver and the kidney in these diabetic rats. SA displayed less efficiency in reducing body weight and food consumption compared to liraglutide. In conclusion, SA effectively activates GLP-1 receptors, resulting in a reduction in diabetic-related complications in rats. Therefore, it is beneficial to develop SA as a chemical agonist for clinical applications in the future.
... Myricetin shows a wide range o benefts on various diseases, such as cancer (Jiang et al., 2019), obesity , diabetes (Y. Li et al., 2017), cardiovascular diseases, neurological disorders (Ahmed et al., 2019), liver injury (Guo et al., 2019), viral inection (Ren et al., 2018), and inammation (Hou et al., 2018). It is reported that myricetin possesses potential anti-inammatory eects on various inammatory injury models via multiple signaling pathways. ...
Myricetin shows great anti‐inflammatory effect on colitis and supplementation with myricetin could improve gut microbiota dysbiosis. It is reported that the abnormal blood glucose condition of prediabetes could aggravate the progression of inflammation. However, there is no report on whether myricetin has the protective effect on inflammation comorbid prediabetes. This study aimed to explore the effect and potential mechanism of myricetin on dextran sulfate sodium (DSS)‐induced colitis in prediabetic mice. Several indexes related to colitis were evaluated on DSS‐induced prediabetic mice. Myricetin intervention improved body weight loss, disease activity index score in DSS‐induced colitis in prediabetic mice. Myricetin alleviated inflammation by inhibiting proinflammatory cytokines and myeloperoxidase production in DSS‐induced colitis in prediabetic mice. Furthermore, myricetin showed recovery of intestinal barrier integrity by increasing the expression of tight junction proteins (ZO‐1, Occludin and Claudin‐1). At the gut microbiota level, myricetin showed protective effects via modulating gut dysbiosis associated with DSS‐induced colitis in prediabetic mice. In addition, myricetin could significantly increase the short chain fatty acids produced by gut microbiota. Myricetin may be serving as a novel therapeutic agent which could be used in the treatment of DSS‐induced colitis in prediabetic patients in the future with its added value as well reported antidiabetic agent.
... Among those flavonoids, quercetin was reported to suppress Entodinium rumen protozoa in vivo without reducing the relative abundance of bacteria or volatile fatty acid concentration (Oskoueian et al., 2013). Regarding myricetin compound, it has been proven to have many positive pharmacological functions against different types of tumors and pathogenic microbial infections, potentially including the COVID-19 virus (Li et al., 2017;Sun et al., 2018;Joshi et al., 2020). In addition, myricetin regulates some disorders related to ACE, eNOS / NO, MAPK, PI3K/AKT/mTOR, GSK-3β, Nrf2/HO-1, IκB/NF-κB and BrdU/NeuN expressions (Lee, 2016;Qiu et al., 2017;Yang et al., 2017). ...
... Glucagon-like peptide 1 (GLP-1) is a receptor that regulates blood glucose levels by promoting insulin synthesis and secretion, inhibiting glucagon secretion, delaying stomach emptying, and promoting satiety. A dose of 250 mg/kg body weight, given twice daily for 40 days to laboratory mice, myricetin depicted glucoregulatory activity through agonizing the GLP-1 receptor, suggesting that the substance may have potential anti-type 2 diabetes mellitus effects [153]. ...
... The cytotoxic effects of these compounds were observed through different mechanisms like stimulation of PI3KAkt pathway [118,209], NFkB nuclear translocation [153,192], reduction of cell proliferation [96,210], expression of MM9, ERK, JNK [100], metastases [97], and AkT posphorylation [114,211]. However, flavonoids block MAPK activation [129,210] as well as the Nrf-2 signaling pathway [116,212] (Figs. 9 and 10). ...
Flavonoids are organic compounds characterized by a range of phenolic structures, which are abundantly present in various natural sources such as fruits, vegetables, cereals, bark, roots, stems, flowers, tea, and wine. The health advantages of these natural substances are renowned, and initiatives are being taken to extract the flavonoids. Apigenin, galangin, hesperetin, kaempferol, myricetin, naringenin, and quercetin are the seven most common compounds belonging to this class. A thorough analysis of bibliographic records from reliable sources including Google Scholar, Web of Science, PubMed, ScienceDirect, MEDLINE, and others was done to learn more about the biological activities of these flavonoids. These flavonoids appear to have promising anti-diabetic, anti-inflammatory, antibacterial, antioxidant, antiviral, cytotoxic, and lipid-lowering activities, according to evidence from in vitro, in vivo, and clinical research. The review contains recent trends, therapeutical interventions, and futuristic aspects of flavonoids to treat several diseases like diabetes, inflammation, bacterial and viral infections, cancers, and cardiovascular diseases. However, this manuscript should be handy in future drug discovery. Despite these encouraging findings, a notable gap exists in clinical research, hindering a comprehensive understanding of the effects of flavonoids at both high and low concentrations on human health. Future investigations should prioritize exploring bioavailability, given the potential for high inter-individual variation. As a starting point for further study on these flavonoids, this review paper may promote identifying and creating innovative therapeutic uses.
... Wistar rats revealed its' glucoregulatory activity. 44 Li et al 45 have proved Myricetin as an active anticancer compound with pharmacological effects on tamoxifen and its metabolites. Rosmarinic acid pharmacokinetic properties are a good recommendation for oral prescription as it has a low acute toxicity value. ...
Epidermal growth factor receptor (EGFR) is a transmembrane protein that belongs to the ErbB/HER-family of tyrosine kinase receptors. Somatic mutations and overexpression of EGFR have been reported to play a vital role in cancer cell development and progression, including cell proliferation, differentiation, angiogenesis, apoptosis, and metastatic spread. Hence, EGFR is an important therapeutic target for the treatment of various types of epithelial cancers. Somatic mutations have led to resistance to clinically approved synthetic EGFR inhibitors. Furthermore, synthetic EGFR inhibitors have been associated with several side effects. Thus, there is a need to develop novel EGFR inhibitors with an acceptable biosafety profile and high efficacy.
Methods
... Myricetin, a kind of flavonoids, is characterized by a pyrogallol B-bring and has been identified as a potential natural GLP-1R agonist that can be orally administered. Besides, myricetin exhibits enhanced biological properties due to its more extensive hydroxylation compared to other flavonols [43,44]. Quercetin [45], luteolin [46], morin and eriodictyol also have exhibited anti-diabetic pharmacological activity [47,48], primarily based on their anti-oxidant effects. ...
There is increasing evidence that the activation of glucagon-like peptide-1 receptor (GLP-1R) can be used as a therapeutic intervention for cognitive disorders. Here, we have screened GLP-1R targeted compounds from Scutellaria baicalensis, which revealed baicalein is a potential GLP-1R small-molecule agonist. Mitophagy, a selective autophagy pathway for mitochondrial quality control, plays a neuroprotective role in multiple cognitive impairment diseases. We noticed that Glp1r knock-out (KO) mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze (MWM) test than their wide-type (WT) counterparts. Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice. Finally, we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1R-dependent manner. Our findings shed light on the importance of GLP-1R for cognitive function maintenance, and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis. Furthermore, we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.
