[Dihydromyricetin improves Parkinson's disease-like lesions in T2DM rats by activating AMPK/ULK1 pathway].

The purpose of this study was to explore the effect and mechanism of dihydromyricetin (DHM) on Parkinson's disease (PD)-like lesions in type 2 diabetes mellitus (T2DM) rats. The T2DM model was established by feeding Sprague Dawley (SD) rats with high-fat diet and intraperitoneal injection of streptozocin (STZ). The rats were intragastrically administered with DHM (125 or 250 mg/kg per day) for 24 weeks. The motor ability of the rats was measured by balance beam experiment, the changes of dopaminergic (DA) neurons and the expression of autophagy initiation related protein ULK1 in the midbrains of the rats were detected by immunohistochemistry, and the protein expression levels of α-synuclein (α-syn), tyrosine hydroxylase (TH), as well as AMPK activation level, in the midbrains of the rats were detected by Western blot. The results showed that, compared with normal control, the rats with long-term T2DM exhibited motor dysfunction, increased α-syn aggregation, down-regulated TH protein expression, decreased number of DA neurons, declined activation level of AMPK, and significantly down-regulated ULK1 expression in the midbrain. DHM (250 mg/kg per day) treatment for 24 weeks significantly improved the above PD-like lesions, increased AMPK activity, and up-regulated ULK1 protein expression in T2DM rats. These results suggest that DHM may improve PD-like lesions in T2DM rats by activating AMPK/ULK1 pathway.

[Effects of dihydromyricetin on high fat diet induced obesity in mice and its mechanism].

OBJECTIVE: To observe the effects of dihydromyricetin (DHM) on obesity induced by high-fat diet in mice, and to explore whether its mechanism of action is related to the promotion of WAT browning. METHODS: Sixty c57bl/6j mice were randomly divided into 6 groups (n=10): ①normal control group (ND group): normal feed feeding; ②Normal control + low dose DHM group (ND+L-DHM group): normal feed feeding was treated with low dose DHM (125 mg/(kg·d)); ③Normal control + high dose DHM group (ND+H-DHM group): normal feed feeding was treated with high dose DHM (250 mg/(kg·d)); ④High-fat diet group (HFD): high-fat diet; ⑤high-fat diet + low-dose DHM group (HFD+L-DHM group): high-fat diet feeding with low-dose DHM; ⑥High-fat diet + high-dose DHM group (HFD+H-DHM group): High-fat diet was treated with high-dose DHM. After 16 weeks, the mice were fasted overnight, blood samples were collected for fasting blood glucose and blood lipids, then the animals were sacrificed, body length was measured, and Lee's index was calculated. After weighing the adipose tissue in the scapula, groin and epididymis, formaldehyde fixation and HE staining were used to observe the fat cells size, immunohistochemistry was used to detect the expression of uncoupling protein 1 (UCP1). The body weight was measured every 4 weeks during the experiment. RESULTS: Compared with the ND group, the body weight of the mice in the HFD group was increased significantly, suggesting that the obese mouse model replicated successfully. In addition, the body fat weight, fat cell diameter, Lee's index and blood glucose of the HFD group were increased significantly, and the expression of UCP1 in the adipocytes was increased. Body weight, fat cell diameter, Lee's index and blood glucose of HFD mice treated with L-DHM and H-DHM were reversed significantly, while the expression of UCP1 in adipocytes was more significantly increased; however, L-DHM and H-DHM had no significant effects on the above indicators in normal mice. CONCLUSION: Dihydromyricetin inhibited high fat diet induced mouse obesity; the mechanism might be associated with promoting WAT browning.