The mechanisms of hydroxy-a-sanshool from Zanthoxyum bungeanum maxim activates AMPK-HIF1-PKM2 pathway to fix the obesity

To explore effects of hydroxy-a-sanshool (HAS) on metabolism disorder and oxidative stress induced by high-fat diet. The 50 SD male rats were divided into normal group (NC), high-fat group (MC) and HAS groups. Some key indexes, metabolites and signaling molecules were determined. The results showed that compared with MC, HAS significantly reduced body weight, contents of TC, TG, LDL-C, HIF-1, ATP, LDH, CPT and CS in liver; increased activity of SOD and CAT in liver and serum. The identified 7 differential metabolites by UPLC/HRMS were enriched to 18 metabolic pathways including ascorbate metabolism, glutathione metabolism, HIF-1 and glucagon pathway. Furtherly, Western blot showed that increased protein abundance of p-AMPK, p-ACC, Nrf2 and HO-1; reduced that of HIF-1a, p-PKM2 (Tyr105) and CPT1A in HAS groups. It was indicated that HAS activates AMPK-HIF1-PKM2 pathway and Nrf2/HO1 pathway to reduce oxidative damage and improve lipid and energy metabolism disorder caused by high-fat diet.