2. Academic Validation
  3. (20S)-protopanaxatriol attenuates Ang II-induced renal injury via PTPN1-mediated AMPK/mTOR signaling pathway

(20S)-protopanaxatriol attenuates Ang II-induced renal injury via PTPN1-mediated AMPK/mTOR signaling pathway

  • J Ginseng Res. 2025 Nov;49(6):652-662. doi: 10.1016/j.jgr.2025.08.009.
Risheng Zhao 1,  Zhuoqun Wang 1,  Chang Liu 1,  Linxin Zhang 1,  Min Zhang 2,  Huizhu Du 3 4,  Gege Yang 1,  Haiming Sun 1,  Wei Liu 1,  Shuang Yan 5,  Mengyang Wang 1
Affiliations

Affiliations

  • 1 Department of Pharmacology, College of Pharmacy, Beihua University, Jilin, Jilin, 132000, China.
  • 2 College of Basic Medicine, Beihua University, Jilin, Jilin, 132000, China.
  • 3 Peking University People's Hospital Qingdao Hospital, No. 1 Jinsheng Road, Chengyang District, Qingdao, 266000, Shandong Province, China.
  • 4 Women and Children's Hospital, Qingdao University, No. 6, Tongfu Road, Shibei District, Qingdao, 266000, Shandong Province, China.
  • 5 Department of Ultrasonography, Integrated Traditional Chinese and Western Medicine Hospital of Jilin City Jilin Province, Jilin, 132000, China.
PMID: 41268307 DOI: 10.1016/j.jgr.2025.08.009
Abstract

Background: (20S)-Protopanaxatriol (PPT), a bioactive triterpenoid from Panax ginseng, has been used in Traditional Chinese Medicine (TCM) to tonify kidney yang and regulate blood pressure. The research aimed to elucidate PPT's protective effects against angiotensin II (Ang II)-induced renal injury.

Methods: A C57BL/6 mouse model of kidney injury was established by continuous infusion of Ang II for 4 weeks using an osmotic minipump. Treatment with PPT was initiated two weeks after Ang II infusion and administered daily for 14 days. Molecular docking, drug affinity response target stability (DARTS), and cellular thermal shift assay (CETSA) were employed to identify and validate potential targets of PPT in alleviating Ang II-induced renal injury. Additionally, biochemical assays, histopathological analysis, and Western blotting were performed to assess renal function, tissue damage, and signaling pathway modulation.

Results: Our findings demonstrated that PPT exerted protective effects against Ang II-induced renal dysfunction in mice by significantly attenuating renal fibrosis and inflammation. Mechanistically, PPT targeted PTPN1 and inhibited the AMPK/mTOR signaling pathway, thereby effectively alleviating Autophagy dysregulation in both renal tissues of mice and Ang II-stimulated NRK-52E cells in vitro. Molecular docking, DARTS, and CETSA experiments confirmed PTPN1 as a direct target of PPT, providing a molecular basis for its renoprotective effects.

Conclusion: These findings validate ginseng's traditional use in kidney disorders and demonstrate PPT's potential as a therapeutic agent for hypertensive nephropathy by targeting PTPN1/AMPK/mTOR signaling. Further clinical exploration is needed to translate these results into practice.

Keywords

(20S)-Protopanaxatriol; AMPK; Angiotensin II; Autophagy; Hypertensive nephropathy; PTPN1; mTOR.

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