Jinlida granules alleviate podocyte apoptosis and mitochondrial dysfunction via the AMPK/PGC-1α pathway in diabetic nephropathy

Traditional Chinese Medicine (TCM) has demonstrated promising efficacy in managing and preventing the early-stage diabetic nephropathy (DN). Although the exact mechanisms remain elusive, clinical evidence has suggested that Jinlida granules (JLD) are beneficial in improving renal function among patients with DN. The present study aimed to elucidate the effect of JLD on DN and the underlying molecular mechanism. Therefore, podocyte apoptosis was evaluated using flow cytometry and TUNEL staining, while mitochondrial morphology and function were assessed using transmission electron microscopy, MitoTracker, JC-1 and reactive oxygen species staining. RNA sequencing analysis was performed to elucidate the mechanism underlying the effect of JLD on DN. Additionally, to investigate the role of peroxisome proliferator-activated receptor-gamma co-activator-1 alpha (PGC-1 alpha) in mitigating JLD-induced mitochondrial dysfunction and podocyte apoptosis, MPC5 cells were transfected with the corresponding small interfering RNA constructs. The results showed that JLD effectively improved renal function and mitigated podocyte injury, as well as ameliorated mitochondrial dysfunction and inhibited apoptosis in db/db mice. In vitro experiments further revealed that JLD exerted a protective effect via inhibiting mitochondrial fission and apoptosis in high glucose-treated podocytes. Furthermore, JLD enhanced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), thus promoting the expression of PGC-1 alpha, eventually improving apoptosis and mitochondrial homeostasis. Overall, the current study revealed that JLD could improve mitochondrial homeostasis and reduce cell apoptosis in podocytes via activating the AMPK/PGC-1 alpha pathway, thus providing a theoretical foundation for the clinical management of DN.