Clinical studies of Dihydromyricetin have confirmed that it has the effect of improving liver function in patients with alcoholic liver injury, and has shown the effect of reducing liver fat content and improving insulin resistance in patients with non-alcoholic fatty liver disease, which can effectively alleviate the symptoms of alcohol discomfort and accelerate alcohol metabolism. In addition, preliminary clinical trials have suggested that it has an adjunctive hypoglycaemic effect in patients with type 2 diabetes. The existing Dihydromyricetin preparations (200-300mg/time) have a good safety profile, but the problem of low bioavailability needs to be solved.

Pharmacological action

-Liver protection

As a plant-derived flavonoid compound, Dihydromyricetin has significant hepatoprotective effects and can effectively improve a variety of liver damage conditions. Studies have shown that compared with the control group, the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the Dihydromyricetin treatment group are reduced, serum albumin (ALB) is significantly increased, and superoxide dismutase (SOD) activity is enhanced, that is, Dihydromyricetin can significantly improve carbon tetrachloride (CCl4)-induced liver injury in mice.

Figure 1 Protective effect of Dihydromyricetin on acute liver injury in mice. (A) ALT levels. (B) AST levels. (C) ALB content. (D) SOD activity.

-Anticancer

Dihydromyricetin, a flavonoid active ingredient derived from plants, has become a research hotspot for its potential anti-tumour effects. A large number of in vitro and in vivo studies have shown that Dihydromyricetin exhibits selective inhibitory effects on breast cancer (MDA-MB-231) and lung cancer (A549) and other malignant tumour cells, and can produce synergistic effects when combined with conventional chemotherapy drugs (such as cisplatin). Studies have shown that Dihydromyricetin significantly inhibits the proliferation of human liver cancer HepG2 cells in a concentration and time dependence, and finally achieves an inhibitory effect on the development of liver cancer.

Figure 2 HepG2 cells were treated with different concentrations of Dihydromyricetin for 24 h, 48 h and 72 h, respectively.

-Hypoglycaemic effect

The flavonoid small molecule compound Dihydromyricetin maintains blood glucose homeostasis by enhancing insulin sensitivity, regulating glucose metabolism enzyme activity, delaying intestinal sugar absorption, and protecting pancreatic islet function. Experiments have confirmed that the 250mg/kg dose can reduce fasting blood glucose by 40-45% in diabetic model rats, which is comparable to Metformin (MET), and has good biosafety and potential clinical application value.

Figure 3 Effects of Dihydromyricetin on glucose metabolism in rats with type 2 diabetes.

-Anti-inflammatory

Dihydromyricetin, a naturally occurring flavonoid small molecule compound, exhibits definite anti-inflammatory effects, mainly by inhibiting numerous inflammatory signalling pathways, changing the levels of various inflammatory factors, and regulating immune cell function. Studies have found that Dihydromyricetin can inhibit the secretion of lipopolysaccharide (LPS)-induced pro-inflammatory factor interleukin-6 (IL-6), while increasing the production of anti-inflammatory factor interleukin-10 (IL-10), and ultimately exert local anti-inflammatory effects.

Figure 4 Effect of Dihydromyricetin on LPS-induced secretion of inflammatory cytokines in RAW264.7 cells. (A-B) IL-6 and IL-10 expression levels.

-Improve obesity effects

The natural active ingredient Dihydromyricetin can exert significant anti-obesity effects by inhibiting adipocyte differentiation, reducing white fat accumulation, promoting lipolysis, reducing visceral fat content, and improving obesity-induced insulin resistance. Experimental data showed that compared with the control group, Dihydromyricetin intervention could significantly reduce adipose tissue weight and blood sugar and other related indicators in high-fat diet-induced obesity model mice, which revealed that Dihydromyricetin had the effect of improving obesity-related body lipid dyslipidemia and glucose metabolism disorders.

Figure 5 Effects of Dihydromyricetin on body fat weight, blood glucose and Lee's index in obese mice fed on a high-fat diet.

-Neuroprotection

Dihydromyricetin is a natural compound with neuroprotective activity that significantly improves the pathological features of a variety of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Studies have shown that Dihydromyricetin has a clear protective effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model and can effectively improve motor dysfunction in model animals, and these results suggest that Dihydromyricetin has potential application value in the treatment of neurodegenerative diseases.

Figure 6 Dihydromyricetin promotes the recovery of motor dysfunction induced by MPTP-induced Parkinson's disease in mice.

 (A) Climbing rod test. (B) Rod rotation test. (C) Average motion speed. (D) Total distance of movement.

-Heart-protective

Dihydromyricetin is a flavonoid naturally contained in plants, which can effectively improve the pathological status of a variety of heart diseases, including myocardial infarction, myocardial fibrosis and myocardial ischaemia-reperfusion injury, etc., and at the same time shows good therapeutic potential, providing a new research direction for the prevention and treatment of cardiovascular diseases. Studies have shown that Dihydromyricetin can significantly inhibit atherosclerotic plaque formation in Apoe−/− mice by inhibiting endothelial activation and promoting endothelial cell NO production.

Figure 7 Anti-atherosclerotic effect of Dihydromyricetin on Apoe-/- mice.

 (A) Quantitative analysis of oil red O staining. (B) ORO-stained plaque area quantification. (C) NO level.

-Other effects

As a natural active ingredient of flavonoids derived from plants, Dihydromyricetin can also effectively delay the process of various ageing models, providing new research directions and application potential for the field of anti-ageing. In addition, its antioxidant activity is mainly manifested in the fact that it can significantly scavenge free radicals and enhance endogenous antioxidant enzyme activity. At the same time, its antibacterial experiments showed that it had a significant inhibitory effect on gram-positive bacteria such as Staphylococcus aureus. Based on these characteristics, Dihydromyricetin has important development and application prospects in the field of functional food and medicine.

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