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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Renal Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1503628
This article is part of the Research Topic Cell Death in Kidney Diseases: Novel Biomarkers, Mechanisms, and Therapeutic Strategies View all 3 articles

Danshen Injection ameliorates unilateral ureteral obstruction-induced renal fibrosis by inhibiting ferroptosis via activating SIRT1/GPX4 pathway

Provisionally accepted
Yiwen Cao Yiwen Cao 1Huan Zhao Huan Zhao 1Shuyin Lin Shuyin Lin 1Junqi Chen Junqi Chen 2Jingli Xiong Jingli Xiong 1Zhijun Zeng Zhijun Zeng 1Ziyu Long Ziyu Long 1Yingru Su Yingru Su 1Yingqi Zhong Yingqi Zhong 1Lingru Zhao Lingru Zhao 1Mingshan Zhang Mingshan Zhang 1Junbiao Wu Junbiao Wu 3Yuan Zhou Yuan Zhou 1Jiuyao Zhou Jiuyao Zhou 1*
  • 1 Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
  • 2 The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
  • 3 The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China

The final, formatted version of the article will be published soon.

    The pathogenesis of renal fibrosis is related to blood stasis, and the method of promoting blood circulation and removing blood stasis is often used as the treatment principle. Danshen injection (DSI) is a commonly used drug for promoting blood circulation and removing blood stasis in clinic. However, whether DSI slows the progression of renal fibrosis or the potential mechanism is uncertain.We investigated renal fibrosis models using UUO mice and TGF-β stimulation in HK-2 cells.Results: Our findings revealed that DSI or Fer-1 alleviated kidney injury by ameliorating renal morphology injury and pathological injury in vivo. Besides, DSI or Fer-1 inhibited renal fibrosis in vivo and in TGF-β-induced HK-2 cells. Furthermore, ferroptosis was lessened under DSI or Fer-1 treatment. More importantly, the DSI active ingredients (danshensu, salvianolic acid B, protocatechuic aldehyde, caffeic acid and tanshinone IIA) could bind to SIRT1. The protein levels of SIRT1 and GPX4 were downregulated accompanied by the incremental concentrations of TGF-β or Erastin, which were repaired by DSI or Fer-1 intervention. However, the inhibition of ferroptosis and renal fibrosis owing to DSI were reversed by SIRT1 inhibitor EX527.Taken together, our results indicated that DSI could protect against ferroptosis to attenuate renal fibrosis by activating the SIRT1/GPX4 pathway. It is expected to be a potential agent to treat renal fibrosis.

    Keywords: Danshen Injection, renal fibrosis, ferroptosis, SIRT1, GPX4 Abbreviations: BUN, Blood urea nitrogen, CKD, chronic kidney disease, DSI, Danshen Injection, ECM, extracellular matrix, EMT, epithelial-mesenchymal transition, Fer-1, ferrostatin-1, GPX4, glutathione peroxidase 4, GSH, Glutathione

    Received: 29 Sep 2024; Accepted: 26 Dec 2024.

    Copyright: © 2024 Cao, Zhao, Lin, Chen, Xiong, Zeng, Long, Su, Zhong, Zhao, Zhang, Wu, Zhou and Zhou. 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: Jiuyao Zhou, Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China

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