Pregnane X receptor activation by its natural ligand Ginkgolide-A improves tight junction proteins expression and attenuates bacterial translocation in cirrhosis

Abstract Background and aims Pregnane X receptor (PXR) is a ligand-activated transcription factor and nuclear receptor expressed ubiquitously along gut-liver-axis. Inflammatory bowel disorders have been reported to implicate PXR in maintaining tight junction (TJ) integrity and countering inflammation. However, the hepatoprotective role of PXR activation in soothing bacterial translocation in liver cirrhosis has not been explored. Ginkgolide A (GA), a terpene trilactone from Ginkgo Biloba extract, is a natural ligand of rodent and human PXR. This study aims to investigate the effect of GA in activating PXR and improving associated tight junction integrity and reducing bacterial translocation in gut-liver axis of CCl4 induced cirrhosis model. Methods Swiss albino mice were administered with CCl4 (0.5 ml/kg body weight, i.p) in corn oil for 12 weeks at an interval of two times a week. Following ascites induction, mice were randomized & administered 100 mg/kg body weight of GA through oral gavage for 2 weeks. At termination, blood, gut and liver tissues were collected for biochemical and molecular studies. Results When compared to naive mice, protein expression of hepatic and small intestinal PXR, CYP3A, ZO-1 and occludin were found to be significantly (p  Conclusion In conclusion, our data supports the hypothesis that, GA treatment to CCl4 induced cirrhotic mice, activated hepatic and small intestinal PXR and diminished inflammation, thereby improving tight junction integrity and attenuating bacterial translocation.