<p>Dihydromyricetin Attenuates Metabolic Syndrome And Improves Insulin Sensitivity By Upregulating Insulin Receptor Substrate-1 (Y612) Tyrosine Phosphorylation In db/db Mice</p>

Abstract

PurposeDihydromyricetin (DHM), the main bioactive flavonoid in vine tea, exerts multiple health beneficial effects. This work aimed to identify whether a naturally derived flavonoid product, DHM, can significantly attenuate metabolic syndrome and improve insulin sensitivity.Methods10-week-old db/db mice were randomly assigned to receive the antidiabetic agent metformin (Met, 50 mg/kg BW), DHM (1.0 g and 0.5 g/kg BW) or placebo and were simultaneously fed a high-fat diet for 8 weeks. The general status of the animals was observed and recorded daily, body weight and blood glucose levels were measured weekly, during the experimental period. On day 55, the oral glucose tolerance test (OGTT) was performed. After OGTT, all animals were anesthetized and sacrificed by cervical decapitation. Blood samples were collected in tubes to detect plasma insulin and the biochemical parameters of lipid metabolism. Pancreas histological changes and islet fibrosis were demonstrated by H&E staining and Masson staining, respectively. Moreover, the expression of insulin receptor substrate-1 and phosphorylated insulin receptor substrate-1 in the insulin signaling pathway was detected by Western blot assay.ResultsThe oral administration of DHM (1.0 g and 0.5 g/kg BW) reduced the fasting blood glucose, serum insulin, and glycated hemoglobin levels and the insulin resistance (HOMA-IR) index. Furthermore, DHM intervention decreased body weight and the serum lipid profile. In addition, DHM treatment also markedly decreased the relative abdominal fat weight. Western blot analysis indicated that DHM upregulated the IRS-1 (Y612) tyrosine phosphorylation, improving insulin resistance. Treatment with dihydromyricetin attenuated the progression of insulin resistance and pancreatic fibrosis in fatty db/db mice.ConclusionIn summary, we determined the antimetabolic syndrome effect of DHM in db/db obese mice. DHM upregulates the IRS-1 (Y612) tyrosine phosphorylation, improving insulin resistance. Therefore, DHM is a promising therapeutic candidate for the control of metabolic syndrome.

Dihydromyricetin Improves Endothelial Dysfunction in Diabetic Mice via Oxidative Stress Inhibition in a SIRT3-Dependent Manner

“…Consistent with previous studies, DHY exerted the hypoglycemic effect in the present study, as evidenced by the decrease in FBG and HbA1c level of STZ-induced diabetic mice. It has been verified that DHY can improve glucose metabolism and insulin sensitivity and ameliorate insulin resistance not only in experimental studies but also in terms of clinical efficacy [ 42 , 43 , 44 ]. DHY has been also proven to attenuate atherosclerosis via improving endothelial dysfunction or through microRNA-21 [ 45 , 46 ] and to protect against ligation-induced carotid artery neointimal formation [ 47 ].…”

Dihydromyricetin Acts as a Potential Redox Balance Mediator in Cancer Chemoprevention

“…The content of DHM in A. grossedentata ranges from 30% to 40% (dry weight), which is considered to have the highest flavonoid content in natural plants [1]. Several scientific investigations reported that DHM possesses various biological activities such as anti-inflammatory [2,3], antioxidative [4,5], anticancer [6,7], antidiabetic [8][9][10], antiatherosclerosis [11,12], and cardioprotective effects [13,14]. The biological properties and the underlying mechanisms of DHM were investigated mostly by in vitro cell cultures and in vivo animal models.…”

Herbal therapy as a promising approach for regulation on lipid profiles: A review of molecular aspects

“…This plant has broadly been used in southern China for folk therapeutic purposes and based on records, VT could remove dampness and heat, enhance blood circulation and diuresis, and resolve channel blockage and blood stasis (J. He et al, 2019). It has been revealed that VT exerts numerous functions, such as anti‐inflammatory (Hou et al, 2015), hepatoprotective (Zeng et al, 2018), and antioxidant properties (Ye et al, 2015).…”