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- Title
Icariin alleviates renal inflammation and tubulointerstitial fibrosis via Nrf2‐mediated attenuation of mitochondrial damage.
- Authors
Ding, Nannan; Sun, Shanyue; Zhou, Shuting; Lv, Zhimei; Wang, Rong
- Abstract
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 superoxide dismutase activity and decreased malondialdehyde level. Additionally, TOMM20 immunofluorescence staining and transmission electron microscope revealed that mitochondrial mass and morphology of tubular epithelial cells in UUO mice was restored by icariin. In HK‐2 cells treated with TGF‐β1, icariin markedly decreased profibrotic proteins expression, inhibited inflammatory factors, and protected mitochondria along with preserving mitochondrial morphology, reducing reactive oxygen species (ROS) and mitochondrial ROS (mtROS) overproduction, and preserving membrane potential. Further investigations demonstrated that icariin could activate nuclear factor erythroid 2‐related factor 2 (Nrf2)/heme oxygenase‐1 (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. Significance statement: Tubulointerstitial fibrosis is an unavoidable consequence of advancing chronic kidney disease (CKD) and imposes a substantial global health burden. However, few effective therapeutic agents are available at present. The present study investigated the ameliorative effects of icariin on tubulointerstitial fibrosis (TIF) both in vivo and in vitro, and demonstrated that icariin inhibited inflammation and oxidative stress, at least partially, through improving Nrf2 activity and subsequent mitochondrial function, and eventually mitigated TIF and preserved renal function, suggesting that icariin could be developed as a promising therapeutic candidate for the treatment of CKD.
- Subjects
NUCLEAR factor E2 related factor; RENAL tubular transport disorders; MITOCHONDRIAL pathology; FETAL hemoglobin; MITOCHONDRIA
- Publication
Cell Biochemistry & Function, 2024, Vol 42, Issue 3, p1
- ISSN
0263-6484
- Publication type
Article
- DOI
10.1002/cbf.4005