Salvianolic acid B protects against ANIT-induced cholestatic liver injury through regulating bile acid transporters and enzymes, and NF-kappa B/I kappa B and MAPK pathways

摘要

The purpose of this study was to investigate the pharmacological effects of salvianolic acid B (SA-B) on alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury with the focus on bile acid homeostasis and anti-inflammatory pathways. Rats were randomly assigned into four groups. The control group was given normal saline (i.p.) for 7 consecutive days and on the 5th day was given the vehicle (i.g.). Model group was treated with normal saline (i.p.) for 7 days and administrated with ANIT (75 mg/kg, i.g.) on the 5th day. The SA-B groups were treated with SA-B (15 mg/kg and 30 mg/kg, i.p.) for 7 consecutive days as well as ANIT (75 mg/kg, i.g.) on the 5th day. We found that the serum levels of ALT, gamma-GT, TBA, and other liver function indexes were found to be lower in the SA-B treatment groups than in the model group. SA-B also upregulated the transporters and enzymes involved in bile acid homeostasis such as Bsep, Oatp2, and Cyp3a2 in rats and BSEP, CYP3A4, and OATP2 in human cell lines. Moreover, SA-B suppressed NF-kappa B translocation into the nucleus, inhibited phosphorylation of p38 and JNK, and inhibited inflammation markers including IL-1 beta, IL-6, TGF-beta, TNF-alpha, and COX-2 to extenuate cholestatic liver injury both in vivo and vitro. Taken together, our findings suggest that anti-cholestatic effects of SA-B may be associated with its ability to regulate NF-kappa B/I kappa B and MAPK inflammatory signaling pathways to inhibit inflammation and regulate transporters and enzymes to maintain bile acid homeostasis.