Regulating Mitochondrial Biogenesis via Pachymaran: A Novel Treatment Strategy for Diabetic Cardiomyopathy

Abstract

Background: Diabetic cardiomyopathy (DCM) is a common complication among diabetic patients, yet its pathogenesis is not fully understood. Mitochondrial dysfunction and oxidative stress play important roles in the development of DCM. Pachymaran (PPS), a natural compound with various biological properties, has not been extensively investigated in DCM. This study aims to explore the role and mechanism of PPS in DCM. Methods: DCM model mice were initially divided into control, DCM, and PPS treatment groups (50 mg/kg and 100 mg/kg). Subsequently, we evaluated the effects of PPS on DCM via myocardial histopathological analysis, cardiac function assessment, and mitochondrial function detection. In addition, Western blot and real-time quantitative PCR were used to study the regulatory effects of PPS on mitochondrial biogenesis and Sirtuin 3 (SIRT3). Results: PPS treatment in DCM mice exhibited significant myocardial protection, evident from reduced myocardial fibrosis upon histopathological examination (p < 0.05). Furthermore, cardiac function assessment revealed a significant improvement in myocardial contractile function in the PPS treatment group (p < 0.01). Moreover, enhanced activity of mitochondrial respiratory chain complexes and ATP synthesis capacity was observed in the PPS treatment group (p < 0.01), indicating improved mitochondrial function. Further research revealed that PPS significantly increased the expression level of SIRT3 and promoted expression of key regulators of mitochondrial biogenesis (p < 0.01). Conclusion: The results of this study indicate that PPS protects against DCM by activating mitochondrial biogenesis and SIRT3. PPS can inhibit myocardial fibrosis, enhance myocardial contractile function, and improve mitochondrial function. Additionally, PPS can regulate SIRT3 expression and promote mitochondrial biogenesis. Therefore, PPS may be a potential drug for DCM treatment, proposing a new strategy for DCM treatment.