Scutellarin Ameliorated Carbon Tetrachloride-Induced Chronic Liver Injury in Mice

Abstract

Background: Erigeron breviscapus (Vant.) Hand. -Mazz. is an edible and traditional medical herb and its extract scutellarin (SCU) is a widely used flavonoid showing anti-oxidant and anti-inflammatory activities. The purpose of this study was to evaluate the hepatoprotective effect of SCU on carbon tetrachloride (CCl4)-induced chronic liver injury in mice and reveal the underlying mechanisms. Methods: Chronic liver injury in mice was induced by intraperitoneal injection of 1 ml/kg CCl4 every three days. SCU (15 mg/kg, 30 mg/kg and 60 mg/kg) was administered through gavage every day. Bifendate (120 mg/kg) serves as a positive drug to validate the effectiveness of SCU.Results: The hepatoprotective effect of SCU was confirmed by liver function analysis, histological analysis and TUNEL assay. Administration of SCU recovered the activities of superoxide dismutase (SOD) and reduced the production of malondialdehyde (MDA). Additionally, treatment with SCU significantly decreased the mRNA levels of pro-inflammatory cytokines including IL-6, IL-1β and TNF-α. Moreover, SCU treatment suppressed the activation of NF-κB by decreasing the degradation of IκBα and inhibited the expression of CYP2E1. The 16S rRNA sequencing demonstrated that intake of SCU significantly remodeled gut microbiota, especially enriching the following: Lactobacillus, Coprobacillus, Akkermansia, Bifidobacterium, Parabacteroides. Conclusion: Our findings showed that SCU effectively ameliorated CCl4-induced chronic liver injury. This hepatoprotective effects might be attributed to inhibition of CCl4-induced NF-κB and CYP2E1 activation and enrichment of beneficial microbial community.