Baoshentongluo Formula relieves podocyte injury in diabetic kidney disease through regulating mitophagy via PINK1/Parkin signaling pathway
IntroductionDiabetic 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 characterist...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1606326/full |
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| author | Yanyu Pang Lei Tian Yufei Liu Yifan Guo Jingwen Zhao Yutong Wang Mengdi Wang Wenjing Zhao |
| author_facet | Yanyu Pang Lei Tian Yufei Liu Yifan Guo Jingwen Zhao Yutong Wang Mengdi Wang Wenjing Zhao |
| author_sort | Yanyu Pang |
| collection | DOAJ |
| description | IntroductionDiabetic 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. MethodsMouse podocyte clone-5 (MPC-5) cells and db/db mice were used. Db/db mice were randomized into db/db and db/db + BSTL (16.5 g/kg/d, intragastric administration for 12 weeks). A group of m/m mice served as the control. Renal function, urinary albumin-to-creatinine ratio (UACR), histopathological analysis, apoptotic, and mitophagy-related protein levels were evaluated. MPC-5 cells were exposed to high glucose (HG, 30 mM) and BSTL drug-containing serum (8%) for 24 h grouping as control, HG, HG + BSTL, and HG + siPINK1. Podocyte apoptosis, mitophagy levels, and expression of PTEN-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (Parkin) were assessed.ResultsIn db/db diabetic mice, oral administration of BSTL significantly lowered urinary albumin-to-creatinine ratio (P<0.05), improved glomerular filtration rate, and ameliorated renal histopathological changes, decreased LC3-II/LC3-I ratio, and downregulated expression of mitophagy-related proteins PINK1, Parkin, ATG5 and Beclin-1. Treatment with 8% BSTL-containing serum significantly attenuated HG-induced podocyte apoptosis (P<0.01) and suppressed excessive mitophagy, as evidenced by reduced TOM20/LC3 co-localization (P<0.01). Notably, BSTL treatment markedly reduced protein levels of both PINK1 and Parkin (P<0.01), key regulators of mitophagy initiation. Genetic silencing of PINK1 in podocytes phenocopied BSTL's protective effects, confirming the pathway specificity. DiscussionOur 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. |
| format | Article |
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| institution | DOAJ |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-e36b0eb1661347ffb64bc0c8dbb6b40e2025-08-20T03:13:27ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-05-011610.3389/fendo.2025.16063261606326Baoshentongluo Formula relieves podocyte injury in diabetic kidney disease through regulating mitophagy via PINK1/Parkin signaling pathwayYanyu Pang0Lei Tian1Yufei Liu2Yifan Guo3Jingwen Zhao4Yutong Wang5Mengdi Wang6Wenjing Zhao7Department of Nephrology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaDepartment of Nephrology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaDongfang Hospital, Beijing University of Chinese Medicine, Beijing, ChinaWangjing Hospital, Beijing University of Chinese Medicine, Beijing, ChinaBeijing Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaBeijing Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Nephrology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaDepartment of Nephrology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaIntroductionDiabetic 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. MethodsMouse podocyte clone-5 (MPC-5) cells and db/db mice were used. Db/db mice were randomized into db/db and db/db + BSTL (16.5 g/kg/d, intragastric administration for 12 weeks). A group of m/m mice served as the control. Renal function, urinary albumin-to-creatinine ratio (UACR), histopathological analysis, apoptotic, and mitophagy-related protein levels were evaluated. MPC-5 cells were exposed to high glucose (HG, 30 mM) and BSTL drug-containing serum (8%) for 24 h grouping as control, HG, HG + BSTL, and HG + siPINK1. Podocyte apoptosis, mitophagy levels, and expression of PTEN-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (Parkin) were assessed.ResultsIn db/db diabetic mice, oral administration of BSTL significantly lowered urinary albumin-to-creatinine ratio (P<0.05), improved glomerular filtration rate, and ameliorated renal histopathological changes, decreased LC3-II/LC3-I ratio, and downregulated expression of mitophagy-related proteins PINK1, Parkin, ATG5 and Beclin-1. Treatment with 8% BSTL-containing serum significantly attenuated HG-induced podocyte apoptosis (P<0.01) and suppressed excessive mitophagy, as evidenced by reduced TOM20/LC3 co-localization (P<0.01). Notably, BSTL treatment markedly reduced protein levels of both PINK1 and Parkin (P<0.01), key regulators of mitophagy initiation. Genetic silencing of PINK1 in podocytes phenocopied BSTL's protective effects, confirming the pathway specificity. DiscussionOur 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.https://www.frontiersin.org/articles/10.3389/fendo.2025.1606326/fulldiabetic kidney diseasetraditional Chinese medicinepodocyteapoptosismitochondria |
| spellingShingle | Yanyu Pang Lei Tian Yufei Liu Yifan Guo Jingwen Zhao Yutong Wang Mengdi Wang Wenjing Zhao Baoshentongluo Formula relieves podocyte injury in diabetic kidney disease through regulating mitophagy via PINK1/Parkin signaling pathway Frontiers in Endocrinology diabetic kidney disease traditional Chinese medicine podocyte apoptosis mitochondria |
| title | Baoshentongluo Formula relieves podocyte injury in diabetic kidney disease through regulating mitophagy via PINK1/Parkin signaling pathway |
| title_full | Baoshentongluo Formula relieves podocyte injury in diabetic kidney disease through regulating mitophagy via PINK1/Parkin signaling pathway |
| title_fullStr | Baoshentongluo Formula relieves podocyte injury in diabetic kidney disease through regulating mitophagy via PINK1/Parkin signaling pathway |
| title_full_unstemmed | Baoshentongluo Formula relieves podocyte injury in diabetic kidney disease through regulating mitophagy via PINK1/Parkin signaling pathway |
| title_short | Baoshentongluo Formula relieves podocyte injury in diabetic kidney disease through regulating mitophagy via PINK1/Parkin signaling pathway |
| title_sort | baoshentongluo formula relieves podocyte injury in diabetic kidney disease through regulating mitophagy via pink1 parkin signaling pathway |
| topic | diabetic kidney disease traditional Chinese medicine podocyte apoptosis mitochondria |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1606326/full |
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