Ligustrazine with telmisartan mitigates the progression of diabetic cardiomyopathy by reducing ER stress, apoptosis, and myocardial fibrosis.

Abstract

Diabetic cardiomyopathy (DCM) is a condition whereby hyperglycemia induces structural, functional, and metabolic changes in the heart, leading to cardiac dysfunction. The renin-angiotensin system plays a pivotal role in the progression of DCM. Ligustrazine (LIG) is an alkaloid from the Chuanxiong plant that has long been used as a "food medicine". The stewed rhizomes, which contain LIG as a major constituent, have proven benefits and have been extensively studied for their anti-apoptotic and anti-fibrotic properties; however, their role in DCM remains unclear. Additionally, whether combining LIG with telmisartan (TEL), an AT1R blocker, offers greater cardiac protection is unclear. The animal experimentation included a single streptozotocin-55 mg/kg, i.p. injection for disease induction. Four weeks post-induction, animals received respective treatments for 4 weeks: Normal control (NC), diabetic control (DC), DC+LIG40 (40 mg/kg, i.p.), DC+LIG80 (80 mg/kg, i.p.), NC+LIG80, DC+T10 (10 mg/kg, p.o.), and DC+LIG40+ T5. The heart and blood samples were collected to assess cardiac markers, including LDH, CK-MB, ANP, and BNP. Cardiac electrical and hemodynamic changes, as well as histological, immunohistochemical, immunofluorescence, qRT-PCR, and apoptotic assays were performed. A combination of LIG40 and TEL5 provided greater cardiac protection, with a significant improvement in cardiac electrical rhythm and hemodynamics, accompanied by a marked reduction in UPR^ER, myocardial apoptosis, and fibrosis, indicating the efficacy of the combination therapy. Combining LIG, a phytopharmaceutical, with TEL offers greater efficacy in DCM, provides a novel therapeutic strategy, and is compelling and holds value in treating DCM.