Taraxacum officinale Extracts Alleviate Anhedonia and Depression by Inhibiting UPR^mt and Mitophagy in the Hippocampi of T2DM Rats

Abstract

Objective: The objective of this study was to determine the effects of Taraxacum officinale extracts on mitochondrial unfolded protein response (UPRmt) and mitophagy in the hippocampi of type 2 diabetes mellitus (T2DM) rats. Materials and Methods: The T2DM model was established by a high-fat high-sucrose diet (HFSD) for 6 weeks and streptozotocin (STZ) administration. The rats were randomly divided into control, model, metformin (100 mg/kg/day), and T. officinale extracts (1,500 mg/kg/day) treatment groups. Fasting plasma glucose (FPG) levels, 2-h postprandial plasma glucose (2hPPG) levels, and sucrose preference rates (SPR) were ascertained. Enzyme-linked immunosorbent assay (ELISA) was used to quantify the levels of superoxide dismutase (SOD) and malonaldehyde (MDA) in the serum. Finally, the expression levels of UPRmt and mitophagy-related proteins were determined via Western blot analysis. Results: Rats in the model group exhibited significantly higher levels of FPG and 2hPPG but lower SPR than those in the control group. Rats in the Taraxacum group had lower FPG and 2hPPG levels and higher SPR than those of the model group. Moreover, clpP, HSP60, PINK-1, Parkin, P62, Beclin-1, and LC3-II/I proteins were significantly upregulated in the rats of the model group, relative to the control group. UPRmt and mitophagy-related proteins were markedly downregulated in rats of the Taraxacum group, relative to the model group. Conclusion: T2DM rats exhibited certain levels of anhedonia and depression, which were effectively alleviated by T. officinale extracts through the downregulation of UPRmt and mitophagy, and also by conferring protection to mitochondrial function. Keywords Taraxacum officinale, T2DM, hippocampus, UPRmt, mitophagy