Myricetin is a natural flavonoid with powerful antioxidant and anti-inflammatory potential commonly found in vegetables, fruits, nuts, and tea. The vital role of this flavonoid in the prevention and treatment of various diseases is evidenced by its ability to reduce inflammation and oxidative stress, maintain tissue architecture, and modulate cell signaling pathways. Thus, this review summarizes recent evidence on myricetin, focusing precisely on its mechanisms of action in various pathogenesis, including obesity, diabetes mellitus, arthritis, osteoporosis, liver, neuro, cardio, and reproductive system-associated pathogenesis. Moreover, it has been revealed that myricetin exhibits anti-microbial properties due to obstructive virulence factors, preventing biofilm formation and disrupting membrane integrity. Additionally, synergistic potential with other drugs and the role of myricetin-based nanoformulations in different diseases are properly discussed. This review seeks to increase the understanding of myricetin's pharmacological potential in various diseases, principally highlighting its effective mechanisms of action. Further wide-ranging research, as well as more randomized and controlled clinical trial studies, should be executed to reconnoiter this compound's therapeutic value, safety, and usefulness against various human pathogenesis.

As a prevalent metabolic disorder, the increasing incidence of diabetes imposes a significant burden on global healthcare. Flavonoids in natural phytochemical products exhibit notable hypoglycemic properties, making them potential alternatives for diabetes treatment. This article summarizes the hypoglycemic properties of flavonoid subcategories studied in recent years, including flavones, isoflavones, flavonols, flavanols, and others. The relevant targets and signal pathways, such as α-amylase, α-glucosidase, insulin receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), PKR-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α (eIF2α)/activation transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP), etc., are also elaborated. Additionally, flavonoids have also been demonstrated to modulate the gut microbiota and its metabolites. Through the aforementioned mechanisms, flavonoids mainly suppress carbohydrate metabolism and gluconeogenesis; facilitate glucose uptake, glycogenesis, and insulin secretion; and mitigate insulin resistance, oxidative stress, inflammation, etc. Notably, several studies have indicated that certain flavonoids displayed synergistic hypoglycemic effects. In conclusion, this article provides a comprehensive review of the hypoglycemic effects of the flavonoids investigated in recent years, aiming to offer theoretical insights for their further exploration.

Type 2 diabetes mellitus (T2DM) is a disorder characterized by insulin resistance, hyperglycemia, and dyslipidemia. Myricetin, a flavonoid found in various plants, has shown potential anti-diabetic effects in murine studies. This meta-analysis aimed to evaluate the impact of myricetin supplementation on glucose metabolism and lipid profiles in mouse models of metabolic diseases.

A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines (PROSPERO: CRD42024591569). Studies involving mice with metabolic disease models and exclusively using myricetin supplementation were checked across four databases (Embase, Scopus, PubMed, and WoS) until 23rd September 2024. The primary outcomes assessed were blood glucose (BG), insulin levels, triacylglycerol (TAG), total cholesterol (TC), HDL, and LDL. A random-effects model was applied to estimate standardized mean differences (SMD), and SYRCLE's risk-of-bias tool for animal studies was used.

Twenty-one studies with 514 mice met the inclusion criteria. Myricetin supplementation significantly reduced BG (SMD = -1.45, CI: -1.91 to -0.99, p < 0.00001, I2 = 74%), insulin (SMD = -1.78, CI: -2.89 to -0.68, p = 0.002, I2 = 86%), TAG (SMD = -2.60, CI: -3.24 to -1.96, p < 0.00001, I2 = 81%), TC (SMD = -1.86, CI: -2.29 to -1.44, p < 0.00001, I2 = 62%), and LDL (SMD = -2.95, CI: -3.75 to -2.14, p < 0.00001, I2 = 74%). However, the effect on HDL was not statistically significant (SMD = 0.71, CI: -0.01 to 1.43, p = 0.05, I2 = 83%).

Myricetin supplementation improved glucose metabolism and lipid profiles in mouse models, suggesting its potential as a therapeutic agent for managing T2DM. However, further research is needed to confirm these findings in human studies.

Abelmoschus manihot (L.) Medic flower (AMf) exhibits both nutritional value and bioactivities such as antioxidative, anti-inflammatory, neuroprotective, cardioprotective, and hepatoprotective effects. The aim of this investigation was to examine the potential impact of three different solvent extracts of AMf: supercritical CO2 extraction extract, water extract, and ethanol extract (AME), on management of diabetes. All three extracts demonstrated significant inhibitory effects on α-glucosidase (IC50 = 157-261 μg/mL) and lipase (IC50 = 401-577 μg/mL) activities while enhancing the α-amylase activity (32.4-41.8 folds at 200 μg/mL). Moreover, all three extracts exhibited notable inhibition of the formation of advanced glycation end-products, including the Amadori products (inhibition rates = 15.7-36.6%) and the dicarbonyl compounds (inhibition rates = 18.6-28.3%). Among the three extracts, AME exhibited the most pronounced inhibitory effect. AME displayed substantial in vitro and intracellular antioxidative activity, and effectively reduced ROS production (135% at 500 μg/mL) in β-cells under hyperglycemic (HG) conditions. AME also enhanced the activity and gene expression of antioxidant enzymes, which were markedly decreased in the HG-induced β-cells. Furthermore, AME protected β-cell viability and maintained normal insulin secretion under HG conditions, likely due to its ability to reduce oxidative stress within β-cells. This study demonstrated the potential of AME in preventing and managing diabetes and its associated complications. Further in vivo research is necessary to thoroughly elucidate the preventive effects and their underlying mechanisms.

Kaempferol (KA), an natural antioxidant of traditional Chinese medicine (TCM), is extensively used as the primary treatment for inflammatory digestive diseases with impaired redox homeostasis. Severe acute pancreatitis (SAP) was exacerbated by mitochondrial dysfunction and abundant ROS, which highlights the role of antioxidants in targeting mitochondrial function. However, low bioavailability and high dosage of KA leading to unavoidable side effects limits clinical transformation. The mechanisms of KA with poor bioavailability largely unexplored, hindering development of the efficient strategies to maximizing the medicinal effects of KA. Here, we engineered a novel thioketals (TK)-modified based on DSPE-PEG2000 liposomal codelivery system for improving bioavailability and avoiding side effects (denotes as DSPE-TK-PEG2000-KA, DTM@KA NPs). We demonstrated that the liposome exerts profound impacts on damaging intracellular redox homeostasis by reducing GSH depletion and activating Nrf2, which synergizes with KA to reinforce the inhibition of inadequate fission, excessive mitochondrial fusion and impaired mitophagy resulting in inflammation and apoptosis; and then, the restored mitochondrial homeostasis strengthens ATP supply for PAC renovation and homeostasis. Interestingly, TK bond was proved as the main functional structure to improve the above efficacy of KA compared with the absence of TK bond. Most importantly, DTM@KA NPs obviously suppresses PAC death with negligible side effects in vitro and vivo. Mechanismly, DTM@KA NPs facilitated STAT6-regulated mitochondrial precursor proteins transport via interacting with TOM20 to further promote Drp1-dependent fission and Pink1/Parkin-regulated mitophagy with enhanced lysosomal degradation for removing damaged mitochondria in PAC and then reduce inflammation and apoptosis. Generally, DTM@KA NPs synergistically improved mitochondrial homeostasis, redox homeostasis, energy metabolism and inflammation response via regulating TOM20-STAT6-Drp1 signaling and promoting mitophagy in SAP. Consequently, such a TCM's active ingredients-based nanomedicine strategy is be expected to be an innovative approach for SAP therapy.

Development of end-stage renal disease is predominantly attributed to diabetic nephropathy (DN). Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue. Nevertheless, the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain.

To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism.

Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk. Subsequently, blood and urine indexes were assessed, along with examination of renal tissue pathology. Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin, periodic acid-Schiff, Masson's trichrome, and Sirius-red. Additionally, high-glucose culturing was conducted on the RAW 264.7 cell line, treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h. In both in vivo and in vitro settings, quantification of inflammation factor levels was conducted using western blotting, real-time qPCR and ELISA.

In db/db mice, administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis. Notably, we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin, along with a decrease in expressions of inflammatory cytokine-related factors. Furthermore, myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha, interleukin-6, and interluekin-1β induced by high glucose in RAW 264.7 cells. Additionally, myricetin modulated the M1-type polarization of the RAW 264.7 cells. Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin. The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002.

This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

Diabetes mellitus is a complex metabolic disease associated with reduced synaptic plasticity, atrophy of the hippocampus, and cognitive decline. Cognitive impairment results from several pathological mechanisms, including increased levels of advanced glycation end products (AGEs) and their receptors, prolonged oxidative stress and impaired activity of endogenous mechanisms of antioxidant defense, neuroinflammation driven by the nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), decreased expression of brain-derived neurotrophic factor (BDNF), and disturbance of signaling pathways involved in neuronal survival and cognitive functioning. There is increasing evidence that dietary interventions can reduce the risk of various diabetic complications. In this context, flavonols, a highly abundant class of flavonoids in the human diet, are appreciated as a potential pharmacological intervention against cognitive decline in diabetes. In preclinical studies, flavonols have shown neuroprotective, antioxidative, anti-inflammatory, and memory-enhancing properties based on their ability to regulate glucose levels, attenuate oxidative stress and inflammation, promote the expression of neurotrophic factors, and regulate signaling pathways. The present review gives an overview of the molecular mechanisms involved in diabetes-induced cognitive dysfunctions and the results of preclinical studies showing that flavonols have the ability to alleviate cognitive impairment. Although the results from animal studies are promising, clinical and epidemiological studies are still needed to advance our knowledge on the potential of flavonols to improve cognitive decline in diabetic patients.

Aging contributes to the progressive loss of cellular biological functions and increases the risk of age-related diseases. Cardiovascular diseases, some neurological disorders and cancers are generally classified as age-related diseases that affect the lifespan of individuals. These diseases result from the accumulation of cellular damage and reduced activity of protective stress response pathways, which can lead to inflammation and oxidative stress, which play a key role in the aging process. There is now increasing interest in the therapeutic effects of edible plants for the prevention of various diseases, including those associated with aging. It has become clear that the beneficial effects of these foods are due, at least in part, to the high concentration of bioactive phenolic compounds with low side effects. Antioxidants are the most abundant, and their high consumption in the Mediterranean diet has been associated with slower ageing in humans. Extensive human dietary intervention studies strongly suggest that polyphenol supplementation protects against the development of degenerative diseases, especially in the elderly. In this review, we present data on the biological effects of plant polyphenols in the context of their relevance to human health, ageing and the prevention of age-related diseases.