2. Academic Validation
  3. Cylindrin from Imperata cylindrica inhibits M2 macrophage formation and attenuates renal fibrosis by downregulating the LXR-α/PI3K/AKT pathway

Cylindrin from Imperata cylindrica inhibits M2 macrophage formation and attenuates renal fibrosis by downregulating the LXR-α/PI3K/AKT pathway

  • Eur J Pharmacol. 2023 May 3;950:175771. doi: 10.1016/j.ejphar.2023.175771.
Xiaoyu Li 1,  Xin Huang 2,  Yongmin Feng 1,  Yaqing Wang 3,  Jibin Guan 4,  Botian Deng 1,  Qiuping Chen 5,  Yanjing Wang 1,  Yongming Chen 1,  Jiahe Wang 6,  Joe Yeong 7,  Junfeng Hao 8
Affiliations

Affiliations

  • 1 Department of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
  • 2 Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, 110022, China.
  • 3 Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, 110000, China.
  • 4 Masonic Cancer Center, University of Minnesota, Minneapolis, 55455, USA.
  • 5 Department of Geriatrics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
  • 6 Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, 110022, China. Electronic address: wangjh1@sj-hospital.org.
  • 7 Institute of Molecular Cell Biology (IMCB), Agency of Science, Technology and Research (A*STAR), Singapore, Singapore; Department of Anatomical Pathology, Singapore General Hospital, Singapore, 169856, Singapore. Electronic address: yeongps@imcb.a-star.edu.sg.
  • 8 Department of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China; Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, 110022, China. Electronic address: ygzhjf85@gmail.com.
PMID: 37146709 DOI: 10.1016/j.ejphar.2023.175771
Abstract

Imperata cylindrica, a medicinal plant used in Traditional Chinese Medicine, has been used to treat chronic kidney disease. Extracts of I. cylindrica display anti-inflammatory, immunomodulatory, and anti-fibrotic properties. However, the active components of the extracts and their protective mechanisms have not been fully elucidated. In this study, we explored the ability of cylindrin, the main active compound extracted from I. cylindrica, to protect against renal fibrosis and to investigate the potential mechanisms involved. At high doses, cylindrin exerted protective effects against folic acid-induced kidney fibrosis in mice. Bioinformatic analysis predicted the LXR-α/PI3K/Akt pathway as a target of regulation by cylindrin. This was supported by our in vitro and in vivo results showing that cylindrin significantly downregulated the expression of LXR-α and phosphorylated PI3K/Akt in M2 macrophages and mouse renal tissues. Furthermore, high-dose cylindrin inhibited M2 polarization of IL-4-stimulated macrophages in vitro. Our results suggest that cylindrin alleviates renal fibrosis by attenuating M2 macrophage polarization through inhibition of the PI3K/Akt pathway via downregulation of LXR-α.

Keywords

Chronic kidney disease; Cylindrin; Macrophage polarization; Renal fibrosis.

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