ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1606326
This article is part of the Research TopicHerbal Medicine for the Treatment of Chronic Metabolic Diseases, Volume IIView all 20 articles
Baoshentongluo Formula relieves podocyte injury in diabetic kidney disease through regulating mitophagy via PINK1/Parkin signaling pathway
Provisionally accepted
- 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
- 2Beijing University of Chinese Medicine, Beijing, Beijing Municipality, China
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Diabetic kidney disease (DKD) progression is strongly associated with podocyte mitochondrial dysfunction. The clinically effective Chinese herbal Baoshentongluo formula (BSTL) has demonstrated significant proteinuria reduction in DKD patients. HPLC-ESI-MS analysis identified characteristic bioactive components in BSTL including astragalosides, rehmanniosides, and tanshinones. However, the molecular mechanisms through which BSTL maintains podocyte homeostasis remain incompletely understood. In this study, we investigated whether BSTL exerts renoprotective effects by modulating the PINK1/Parkin-mediated mitophagy pathway. Using high glucose (HG, 30 mM)-stimulated mouse podocyte clone-5 (MPC-5) cells, we found that treatment with 8% BSTL-containing serum for 24 hours significantly attenuated HG-induced podocyte apoptosis (P<0.01) and suppressed excessive mitophagy, as evidenced by reduced TOM20/LC3 colocalization (P<0.01), decreased LC3-II/LC3-I ratio, and downregulated expression of autophagyrelated proteins ATG5 and Beclin-1. Notably, BSTL treatment markedly reduced protein levels of both PINK1 and Parkin (P<0.01), key regulators of mitophagy initiation. In db/db diabetic mice, oral administration of BSTL (16.5 g/kg/day) for 12 weeks significantly lowered urinary albumin-tocreatinine ratio (P<0.05), improved glomerular filtration rate, and ameliorated renal histopathological changes. Genetic silencing of PINK1 in podocytes phenocopied BSTL's protective effects, confirming the pathway specificity. Our integrated in vitro and in vivo findings establish that BSTL protects against DKD progression by selectively inhibiting PINK1/Parkin-dependent mitophagy in podocytes to inhibit podocyte injury, which provides both mechanistic insights and therapeutic potential for clinical DKD management.
Keywords: diabetic kidney disease1, Traditional Chinese medicine2, podocyte3, apoptosis4, mitochondria5
Received: 05 Apr 2025; Accepted: 30 Apr 2025.
Copyright: © 2025 Pang, Tian, Liu, Guo, Zhao, Wang, Wang and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mengdi Wang, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
Wenjing Zhao, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
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