Drug Design, Development and Therapy (Feb 2020)
Silibinin Augments the Antifibrotic Effect of Valsartan Through Inactivation of TGF-β1 Signaling in Kidney
Abstract
Ronggui Liu, Qinqin Wang, Zhaoyan Ding, Xiaojuan Zhang, Yunping Li, Yichen Zang, Guijun Zhang Department of Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, People’s Republic of ChinaCorrespondence: Guijun ZhangDepartment of Ultrasound, The Affiliated Hospital of Qingdao University, 1677 Wutaishan Road, Huangdao District, Qingdao, Shandong 266003, People’s Republic of ChinaEmail [email protected]: Chronic kidney disease (CKD) has become a major public health issue. Meanwhile, renal fibrosis caused by diabetic nephropathy can lead to CKD, regardless of the initial injury. It has been previously reported that silibinin or valsartan could relieve the severity of renal fibrosis. However, the effect of silibinin in combination with valsartan on renal fibrosis remains unclear.Material and Methods: Proximal tubular cells (HK-2) were treated with TGF-β 1 (5 ng/mL) to mimic in vitro model of fibrosis. The proliferation of HK-2 cells was tested by CCK-8. Epithelial-mesenchymal transition (EMT) and inflammation-related gene and protein expressions in HK-2 cells were measured by qRT-PCR and Western-blot, respectively. ELISA was used to test the level of TNF-αNF-A. Additionally, HFD-induced renal fibrosis mice model was established to investigate the effect of silibinin in combination with valsartan on renal fibrosis in vivo.Results: Silibinin significantly increased the anti-fibrosis effect of valsartan in TGF-β 1-treated HK-2 cells via inhibition of TGF-β 1 signaling pathway. Furthermore, silibinin significantly enhanced the anti-fibrosis effect of valsartan on HFD-induced renal fibrosis in vivo through inactivation of TGF-β 1 signaling pathway.Conclusion: These data indicated that silibinin markedly increased anti-fibrosis effect of valsartan in vitro and in vivo. Thus, silibinin in combination with valsartan may act as a potential novel strategy to treat renal fibrosis caused by diabetic nephropathy.Keywords: combination, silibinin, renal fibrosis, TGF-β 1 signaling pathway
