SKLB023 hinders renal interstitial fibrosis in obstructive nephropathy by interfering TGF-β1/Smad3 signaling

Abstract

The novel small-molecule inhibitor of iNOS (SKLB023) hindered renal interstitial fibrosis in vivo and in vitro by interfering with TGF-β1/Smad3 signaling, highlighting that SKLB023 has potential in the therapeutic strategy for renal fibrosis.

<p>Mixed micelles loaded with the 5-benzylidenethiazolidine-2,4-dione derivative SKLB023 for efficient treatment of non-alcoholic steatohepatitis</p>

“…These results encourage us to develop novel agents for the treatment of NASH and other inflammatory diseases related to nitric oxide and iNOS. We recently showed that the novel 5-benzylidenethiazolidine-2,4-dione based-derivative SKLB023 (Figure 1) reduced inflammation in rheumatoid arthritis,15–17 and that it significantly attenuated hepatic lipid accumulation, inflammation, and fibrosis in NASH 18. However, the aqueous solubility of SKLB023 was only 4 μg/mL, which limited the administration route to gavage.…”

SKLB023 as an iNOS inhibitor alleviated liver fibrosis by inhibiting the TGF-beta/Smad signaling pathway

“…15 In our previous studies, SKLB023 was found to exhibit excellent anti-inammatory activity in arthritis and antibrotic effects in renal interstitial brosis. 16,17 However, the efficacy of SKLB023 in chronic liver diseases remains undetermined. Thus, in the present study, we use methionine/choline-decient (MCD) diet-induced NASH mice and LX-2 cells to investigate the in vivo and in vitro inhibition of liver brosis by SKLB023, respectively, and the associated mechanism.…”

Protective effects of SKLB023 on a mouse model of unilateral ureteral obstruction by the modulation of gut microbiota

“… 35 In the kidney of UUO mice, SKLB023 also could hinder renal interstitial fibrosis by interfering with TGF-β1/Smad3 signaling pathway. 36 However, the protective effects of SKLB023 on UUO mice model by modulating gut microbiota remains unclear.…”