2. Academic Validation
  3. Shen-Shuai-II-Recipe inhibits tubular inflammation by PPARα-mediated fatty acid oxidation to attenuate fibroblast activation in fibrotic kidneys

Shen-Shuai-II-Recipe inhibits tubular inflammation by PPARα-mediated fatty acid oxidation to attenuate fibroblast activation in fibrotic kidneys

  • Phytomedicine. 2024 Feb 12:126:155450. doi: 10.1016/j.phymed.2024.155450.
Meng Wang 1,  Lingchen Wang 2,  Liang Zhou 2,  Yizeng Xu 2,  Chen Wang 3
Affiliations

Affiliations

  • 1 Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; TCM institute of kidney disease, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: twsa927101@163.com.
  • 2 Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; TCM institute of kidney disease, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • 3 Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; TCM institute of kidney disease, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: chenwang42@126.com.
PMID: 38368794 DOI: 10.1016/j.phymed.2024.155450
Abstract

Background: Shen Shuai Ⅱ Recipe (SSR) is clinically used to treat chronic kidney diseases (CKDs) with remarkable efficacy and safety. In earlier research, we found the anti-inflammatory, antioxidant, and mitochondrial protective properties of SSR in hypoxic kidney injury model, which is closely related to its renal protection. Further work is needed to understand the underlying molecular mechanisms.

Purpose: Further investigation of the mechanisms of action of SSR against renal interstitial fibrosis (RIF) building on previous research leads.

Methods: Rats receiving CKD model surgery were given with Fenofibrate or SSR once a day for eight weeks. In vitro, the NRK-52E cells were treated with SSR in the presence or absence of 10 μM Sc75741, 0.5 μM PMA, or 1 μM fenofibrate under 1% O2. The effects of SSR on NF-κB/NLRP3 inflammatory cascade, secretion of pro-inflammatory cytokines, fatty acid oxidation (FAO), and renal tubular injury were determined by immunoblotting, luminex liquid suspension chip assay, transmission electron microscopy, and Oil red O staining. Next, we delivered PPARα-interfering sequences to kidney tissue and NRK-52E cells by adeno-associated virus (AAV) injection and siRNA transfection methods. Finally, we evaluated the effect of renal tubular cells on fibroblast activation by co-culture method.

Results: SSR attenuated the release of IL-18, VEGF, and MCP1 cytokines, inhibited the activation of NF-κB/NLRP3 cascade, increased the PPARα, CPT-1α, CPT-2, ACADL, and MCAD protein expression, and improved the lipid accumulation. Further studies have demonstrated that one of the ways in which SSR suppresses the inflammatory response to protect renal tubular cells is through the restoration of PPARα-mediated FAO. In addition, by means of co-culture ways, the results demonstrated that SSR attenuated secretion of inflammatory mediators in NRK-52E cells by PPARα/NF-κB/NLRP3 pathway, thereby inhibiting renal fibroblast activation.

Conclusion: SSR inhibits RIF by suppressing inflammatory response of hypoxia-exposed RTECs through PPARα-mediated FAO.

Keywords

Crosstalk; Fatty acid oxidation; Hypoxia; Inflammatory response; Shen Shuai Ⅱ Recipe.

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