2. Academic Validation
  3. Chaihuang Yishen Granule ameliorates mitochondrial homeostasis by upregulating PRDX5/TFAM axis to inhibit renal fibrosis in CKD

Chaihuang Yishen Granule ameliorates mitochondrial homeostasis by upregulating PRDX5/TFAM axis to inhibit renal fibrosis in CKD

  • Phytomedicine. 2025 Jan 30:139:156426. doi: 10.1016/j.phymed.2025.156426.
Ling-Hui Xu 1,  Rui-Zhi Tan 1,  Jing-Yi Lin 1,  Tong Li 1,  Jian Jia 1,  Li-Hua Wu 2,  Rui Wang 2,  Yu-Heng He 2,  Hong-Wei Su 3,  Ping Li 4,  Li Wang 5
Affiliations

Affiliations

  • 1 Research Center of Intergated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China.
  • 2 College of integrational Chinese and western medicine, Southwest Medical University, Luzhou, Sichuan 646000, China.
  • 3 Department of Urology Surgery, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China.
  • 4 Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China. Electronic address: lp8675@163.com.
  • 5 College of integrational Chinese and western medicine, Southwest Medical University, Luzhou, Sichuan 646000, China. Electronic address: wangli120@swmu.edu.cn.
PMID: 39955823 DOI: 10.1016/j.phymed.2025.156426
Abstract

Background: Chaihuang Yishen Granules (CHYS) has been clinically proven to be effective for the treatment of chronic kidney disease (CKD), yet its underlying molecular mechanisms remain largely unexplored.

Objective: To explore the innovative mechanisms by which CHYS alleviates CKD, focusing on its role in modulating PRDX5/TFAM-mediated mitochondrial homeostasis in renal cells.

Methods: In this study, CKD mouse model was established by unilateral ureteral obstruction (UUO) and adenine (Ade) diet. Treatment interventions were administered by gavage with CHYS at doses of 3.8g/kg (low dose) and 7.6g/kg (high dose). The ameliorative effects of CHYS on CKD were evaluated by changes in renal function, kidney tissue structure, renal fibrosis, and mitochondrial dysfunction markers. Tert‑butyl hydroperoxide (t-BHP)-induced oxidative stress in TCMK1 cells was used to simulate CKD renal fibrosis induced by mitochondrial dysfunction in vitro.

Results: CHYS significantly improves renal function and mitigates fibrosis while restoring mitochondrial homeostasis. Notably, PRDX5 expression, which is markedly reduced in CKD patients and mouse models, is substantially upregulated following CHYS treatment. Meanwhile, we demonstrate that ultrasound microbubble-mediated in situ overexpression of PRDX5 confers considerable renal protection in the UUO model. In vitro data show that CHYS effectively prevents t-BHP-induced mtDNA leakage in renal tubular cells, preserving mitochondrial function and stability, an effect compromised by PRDX5 knockdown. Moreover, our protein binding assays uncover a previously unreported interaction between PRDX5 and TFAM, with TFAM knockdown reversing the mitochondrial functional and fibrotic improvements achieved through PRDX5 overexpression and CHYS intervention.

Conclusion: These findings introduce a pioneering perspective on CHYS's mechanism of action. CHYS enhance TFAM activation through PRDX5 upregulation, counteract ROS-induced mitochondrial damage, and restoring mitochondrial homeostasis, and alleviates the progression of renal fibrosis in CKD, highlighting the innovative therapeutic potential of CHYS in mitochondrial-related renal pathologies.

Keywords

Chaihuang Yishen Granule; Chronic kidney disease; Mitochondrial function; PRDX5; ROS; TFAM.

Figures
Products
Inhibitors & Agonists
Other Products