Silibinin enhances anti-renal fibrosis effect of MK-521 via downregulation of TGF-β signaling pathway.
Hum Cell. 2020 Jan 18. Epub 2020 Jan 18. PMID: 31953678
Renal fibrosis is a common characteristic of chronic kidney disease (CKD), and it can lead to end-stage renal disease. It has been reported that silibinin or lisinopril (MK-521) can inhibit the progression of renal fibrosis. However, the effect of combination of silibinin with MK-521 on renal fibrosis remains unclear. Therefore, this study aimed to explore the combination of silibinin with MK-521 on renal fibrosis in vitro and in vivo. The cell viability of HK-2 was detected by CCK-8. The gene and protein expression in HK-2 cells were detected by qRT-PCR and Western blot, respectively. Moreover, HFD-induced renal fibrosis mouse model was established to investigate the effect of silibinin in combination with MK-521 on renal fibrosis in vivo. The expressions of collagen I,α-SMA, Smad2 and Smad3 in TGF-β-treated HK-2 cells were notably decreased by MK-521, which was further inhibited in the presence of silibinin. In addition, we found that silibinin significantly enhanced anti-fibrotic effect of MK-521 on HFD-induced renal fibrosis mice. These findings demonstratedthat silibinin could significantly increase anti-fibrotic effect of MK-521 in vitro and in vivo. Therefore, the combination of silibinin with MK-521 may serve as a potential strategy for the treatment of renal fibrosis.