BTT-105 ameliorates hepatic fibrosis in non-alcoholic fatty liver animal model
- 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
- Issue Date
- Nov-2021
- Publisher
- WILEY
- Keywords
- BTT-105; fibrosis; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; Nrf2
- Citation
- FASEB JOURNAL, v.35, no.11, pp.1 - 19
- Indexed
- SCIE
SCOPUS
- Journal Title
- FASEB JOURNAL
- Volume
- 35
- Number
- 11
- Start Page
- 1
- End Page
- 19
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/140511
- DOI
- 10.1096/fj.202002656RRR
- ISSN
- 0892-6638
- 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.
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