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Icariin alleviates renal inflammation and tubulointerstitial fibrosis via Nrf2-mediated attenuation of mitochondrial damage
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  • Nannan Ding,
  • Shanyue Sun,
  • Shuting Zhou,
  • Zhimei Lv,
  • Rong Wang
Nannan Ding
Shandong Provincial Hospital
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Shanyue Sun
Shandong Provincial Hospital
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Shuting Zhou
Shandong Provincial Qianfoshan Hospital
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Zhimei Lv
Shandong Provincial Hospital

Corresponding Author:[email protected]

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Rong Wang
Shandong Provincial Hospital
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Tubulointerstitial fibrosis is an inevitable consequence of all progressive chronic kidney disease (CKD) and contributes to a substantial health burden worldwide. Icariin, an active flavonoid glycoside obtained from Epimedium species, exerts potential antifibrotic effect. The study aimed to explore the protective effects of icariin against tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO)-induced CKD mice and TGF-β1-treated HK-2 cells, and furthermore, to elucidate the underlying mechanisms. The results demonstrated that icariin significantly improved renal function, alleviated tubular injuries, and reduced fibrotic lesions in UUO mice. Furthermore, icariin suppressed renal inflammation, reduced oxidative stress as evidenced by elevated SOD activity and decreased MDA level. Additionally, TOMM20 immunofluorescence staining and transmission electron microscope revealed that mitochondrial mass and morphology of tubular epithelial cells in UUO mice was improved by icariin. In HK-2 cells treated with TGF-β1, icariin markedly decreased profibrotic proteins expression, inhibited inflammatory factors, and protected mitochondria along with improving mitochondrial morphology, reducing reactive oxygen species (ROS) and mitochondrial ROS (mtROS) overproduction, and preserving membrane potential. Further investigations demonstrated that icariin could activate Nrf2/HO-1 pathway both in vivo and in vitro, whereas inhibition of Nrf2 by ML385 counteracted the protective effects of icariin on TGF-β1-induced HK-2 cells. In conclusion, icariin protects against renal inflammation and tubulointerstitial fibrosis at least partly through Nrf2-mediated attenuation of mitochondrial dysfunction, which suggests that icariin could be developed as a promising therapeutic candidate for the treatment of CKD.
Submitted to Cell Biochemistry & Function
25 Feb 2024Review(s) Completed, Editorial Evaluation Pending
25 Feb 2024Editorial Decision: Revise Major
10 Mar 2024Reviewer(s) Assigned
27 Mar 2024Editorial Decision: Accept