Leonurine ameliorates kidney fibrosis via suppressing TGF-β and NF-κB signaling pathway in UUO mice.
Fibrosis is one of the characteristic features of chronic kidney disease (CKD). Inflammatory reactions and oxidative stress are implicated in the pathogenesis of fibrosis of CKD. Leonurine (LEO) is one of the active compounds from Herba leonuri. In this study, we further evaluated its renoprotective effect in a mouse unilateral urethral obstruction (UUO), featuring the renal tubulointerstitial fibrosis and inflammation. In this model, pretreat of LEO before ureteral obstruction abolished the expression of fibronectin, suppressed the expression of α-SMA and type I/III collagen and down-regulated vimentin. LEO also modified the cytokine expression of TGF-β, TNF-α, IL-6 and IL-1β and suppressed the phosphorylation of Smad3. Moreover, LEO blocked phosphorylation of NF-κB, and inactivated the signaling pathways associated with the progression of kidney inflammatory response. Our data support that LEO is a candidate renoprotective compound for renal fibrosis through targeting the TGF-β/Smad3 and NF-κB pathway.
Translational Medicine Research Center, Nanjing University of Chinese Medicine, Nanjing, PR China.
Haibo
H
Cheng
Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
Yun
Y
Bo
Translational Medicine Research Center, Nanjing University of Chinese Medicine, Nanjing, PR China.
Weixing
W
Shen
Translational Medicine Research Center, Nanjing University of Chinese Medicine, Nanjing, PR China.
Jiani
J
Tan
Translational Medicine Research Center, Nanjing University of Chinese Medicine, Nanjing, PR China.
Zhirong
Z
Jia
Translational Medicine Research Center, Nanjing University of Chinese Medicine, Nanjing, PR China. Electronic address: cl.xu81@gmail.com.
Changliang
C
Xu
Kidney Institute of People's Liberation Army, Xinqiao Hospital, The Third Military Medical University, Chongqing, PR China. Electronic address: lfr199839@163.com.
Furong
F
Li
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005355:Fibrosis; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014524:Urethral Obstruction / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D020011:Protective Agents; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; C013587:leonurine; D005707:Gallic Acid
Fibrosis; Leonurine; NF-κB; Nephroprotective effect; TGF-β; UUO