The protective effect of celastrol in ANIT-induced cholestasis

Purpose: The goals of this study was to (1) evaluate the protective effect of celastrol on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis and (2) which genes were recovered by celastrol. Methods:To investigate the protective effect of celastrol on ANIT-induced cholestasis, the WT mice were randomly assigned into two groups, respectively (n=3): (1) ANIT; (2) ANIT+Celastrol. ANIT+Celastrol group was orally treated with celastrol (10 mg/kg dissolved in 1% DMSO + 2% Tween 80 + 97% water) for 5 consecutive days. After celastrol was treated for 3 days, ANIT and ANIT+Celastrol groups were given a single oral dose of ANIT. All mice were killed 48 h after ANIT administration. Liver samples were harvested and frozen at -80 °C before analysis. Results: A total of 978 DEGs were identified. Large numbers of these DEGs were related to activation of SIRT1, which included increased FXR signaling and inhibition of PPARγ, nuclear factor-kappa B (NF-κB), and P53 signaling. Conclusions: Celastrol could protect ANIT-induced cholestasis by recovering disrupted Sirt1 level. 6 hepatic mRNA profiles were generated by deep sequencing, in triplicate, using Illumina GAIIx.