Heqi San alleviates diabetic atherosclerosis and alters serum metabolic profiles in rats.

BACKGROUND: Heqi San has shown therapeutic potential in the treatment of diabetes. This study aimed to explore the mechanism underlying the effects of Heqi San in treating rats with diabetic atherosclerosis (AS). METHODS: We established a model of atherosclerosis in diabetic rats and treated them with Heqi San. Body weight, food intake, and water intake were measured every two weeks. Subsequently, we examined the effects of Heqi San on serum biochemical markers, aortic structure, fat accumulation, and serum levels of inflammatory factors. The levels of p-AMPK and AMPK in thoracic aorta tissue were evaluated by western blotting. Mass spectrometry was used to identify differential serum metabolites after Heqi San treatment. RESULTS: Intragastric administration of Heqi San enhanced food intake and reduced the excessive water intake caused by diabetic atherosclerosis. Both low and high doses of Heqi San decreased elevated levels of TG, TC, LDL, GLU, and insulin, while increasing HDL levels. Additionally, the AS group showed increased expression of CD68 and CCL-2 in thoracic aorta tissue, along with elevated serum levels of IL-6, IL-1β, and TNF-α. Treatment with Heqi San reduced these inflammatory markers. Heqi San also increased p-AMPK expression in thoracic aorta tissue. Mass spectrometry analysis revealed that the AS group had significantly elevated serum levels of L-NIL, Gln_Cys_Asp, and Geshoidin, whereas high-dose Heqi San treatment decreased the levels of these metabolites. CONCLUSIONS: Heqi San could alleviate atherosclerosis in diabetic rats, and this effect may be associated with changes in serum metabolites such as L-NIL, Gln_Cys_Asp, and Geshoidin.