BTT‐105 ameliorates hepatic fibrosis in non‐alcoholic fatty liver animal model. Issue 11 (25th October 2021)

• Record Type: Journal Article
• Authors: Kim, Hye Young; Ahn, Sang Bong; Hong, Jeong‐Min; Oh, Ju Hee; Saeed, Waqar Khalid; Kim, Gyu Sik; Kim, Hyun; Kang, Jong Koo; Kang, Sukmo; Jun, Dae Won
• Is Part Of: FASEB journal. Volume 35:Issue 11(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-10-25
• Subjects: BTT‐105 -- fibrosis -- non‐alcoholic fatty liver disease -- non‐alcoholic steatohepatitis -- Nrf2; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202002656RRR
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: BTT‐105 (1‐O‐hexyl‐2, 3, 5‐trimethylhydroquinone), a hydroquinone derivative, is a potent anti‐oxidant that was safe and tolerable in phase I clinical trial. This study examined the anti‐fibrotic effect of BTT‐105 in a mouse model of non‐alcoholic fatty liver disease (NAFLD) along with the underlying mechanisms. In vivo, efficacy of BTT‐105 evaluated from three kinds of NAFLD models (methionine/choline deficient diet (MCD), high fat diet (HF) and western diet (WD)). Metabolomics and transcriptomics profiling analysis in liver tissues were conducted. In vitro, anti‐fibrotic effect of BTT‐105 assessed in human hepatic stellated cells (HSCs) and primary mouse HSCs. BTT‐105 improved NAFLD activity score in three kinds of NAFLD animal models (MCD, HF, and WD). BTT‐105 also decreased levels of hepatic pro‐collagen and collagen fibers deposition in liver tissue. Metabolome and transcriptome analysis revealed that BTT‐105 decreased lipid metabolites and increased antioxidants in NAFLD mice. In HepG2 cells, BTT‐105 enhanced Nrf2‐ARE reporter activity in a dose‐dependent manner and increased the levels of antioxidant gene expression. BTT‐105 showed inhibition of HSCs activation and migration. Gene expression profiling and protein expression showed that BTT‐105 increased Nrf2 activation as well as decreased PI3K‐Akt pathway in activated HSCs. BTT‐105 attenuated ameliorates steatohepatitis and hepatic fibrosis.