Berberine reverses LPS-induced repression of CYP7A1 through an anti-inflammatory effect / 中草药·英文版

ABSTRACT

Objective: To evaluate the anti-inflammatory effect of berberine (BBR) on the lipopolysaccharide (LPS)-induced acute phase response and its modulation of the altered bile acid metabolism induced by LPS treatment. Methods: An acute phase response was induced by intraperitoneal injection of LPS (5 mg/kg, ip) in C57BL/6 J mice, and the BBR treatment group was orally administered with BBR (200 mg/ky, ig). The levels of TNFα, IL-1β and IL-6 in the serum were measured using an ELISA kit, and their expression levels in the liver were measured using qRT-PCR. The bile acid pool was measured using a commercial bile acid kit, and the expression levels of enzymes involved in bile acid metabolism were measured by qRT-PCR. The expression levels of CYP7A1, p65 NF-κB and the MAPK signaling pathway was measured using Western blotting. Results: LPS treatment suppressed the expression of CYP7A1 and CYP8B1, and the total bile acid pool was also reduced. Pretreatment with BBR inhibited the pro-inflammatory biomarkers TNFα and IL-1β in the serum, as well as the expression of TNFα, IL-1β and iNOS mRNA in the liver. BBR treatment did not affect the reduction in the bile acid pool size induced by LPS, but significantly increased the concentration of bile acids in the liver, which was consistent with the upregulated expression of CYP7A1 and CYP8B1. The MAPK signaling pathway was activated by BBR treatment, while the p65 NF-κB signaling pathway was inhibited. Conclusion: BBR can offer an anti-inflammatory effect and reverse the inhibition of CYP7A1 and CYP8B1 expression caused by LPS treatment, as well as induce the production of bile acids in liver, probably via MAPK signaling; However, treatment with BBR had no effect on the size of total bile acid pool.