Nuciferine prevents hepatic steatosis associated with improving intestinal mucosal integrity, mucus-related microbiota and inhibiting TLR4/MyD88/NF-κB pathway in high-fat induced rats

Abstract

Nonalcoholic fatty liver disease (NAFLD) has been demonstrated to be closely associated with intestinal barrier functions. The aim of this study is to investigate the effects of nuciferine on preventing hepatic steatosis with relation to intestinal barrier functions in HFD-fed rats. The results showed nuciferine mitigated body weight gain, hyperlipemia and hepatic steatosis with regulating lipid metabolic gene expressions. Meanwhile, nuciferine decreased LPS-induced inflammation through inhibiting TLR4/MyD88/NF-κB pathway and reinforced intestinal barriers through increasing occludin and zonula occluden-1 expression, goblet cells, mucin2 (MUC2) expression. Furthermore, we found that nuciferine changed the relative abundance of mucus-related microbiota (Akkmensia muciniphila, Ruminococcaceae) and LPS-producing microbiota (Desulfovibrionaceae), increased the concentration of fecal acetic acid and propionic acid accompanied by decreased fecal pH. Together, anti-NAFLD effects of nuciferine are related to improving multiple intestinal barrier functions. These findings imply that nuciferine could be a promising agent for NAFLD with a target towards gut-liver axis.

Keywords

• Nuciferine
• Hepatic steatosis
• Intestinal mucosal integrity
• Akkmensia muciniphila
• TLR4/MyD88/NF-κB