Hepatoprotective effect of Physalis divaricata in paracetamol induced hepatotoxicity: In vitro, in silico and in vivo analysis

Ethnopharmacological relevance: Physalis divaricata D. Don. is an erect weed of family Solanaceae. The root extract of this plant is used by the indigenous communities of Sub-Himalayan region of Uttarakhand, India for the treatment of liver disorders. Aim of the study: To evaluate hepatoprotective potential of P. divaricata in paracetamol (PCM) induced hepatotoxicity in rats. Materials and methods: The dried roots of P. divaricata were subjected to extraction using different solvents. The chloroform extract, methanol extract and bioactive aqueous fraction of methanol extract were evaluated for hepatoprotective effect. After initial in vitro screening, all extracts were screened for hepatoprotective potential in PCM (3 g/kg p.o) induced hepatotoxicity. Following PCM administration, extracts were administered orally for 7 days in increasing dose concentrations. All the animals were euthanized on eighth day, serum and liver tissues were collected and subjected to various biochemical and histopathological analysis. Aqueous fraction of methanol extract was further analyzed using LC-MS analysis. Results: Methanol extract and its bioactive aqueous fraction exhibited significant and better in vitro antioxidant and antiproliferative activity as compared to chloroform extract. PCM treatment caused hepatotoxicity as assessed by altered levels of various hepatic biomarkers (increase in the levels of ALT, AST, ALP, albumin, triglycerides, cholesterol, TBARS, and AOPPs as well as decrease in GSH and TrxR levels) along with histopathological changes (portal to portal bridging, necrosis, and inflammation). Methanolic extract (200, 400 and 800 mg/kg) and its aqueous fraction treatment (25, 50 and 100 mg/kg) significantly restored elevated hepatic biomarkers, oxidative stress, and protected normal hepato-architecture. LC-MS analysis of aqueous fraction showed presence of rutin and kaempferol. In silico analysis further showed the capability of rutin to make complex with TNF-alpha and block its interaction with the target site. Conclusion: Aqueous fraction showed maximum hepatoprotective potential as conceived through in vitro and in vivo studies. Presence of rutin may explain hepatoprotective potential of P. divaricata.

Automated summary

This study evaluated the hepatoprotective potential of P. divaricata in paracetamol-induced hepatotoxicity in rats. The methanol extract and its bioactive aqueous fraction showed better antioxidant and antiproliferative activity compared to the chloroform extract in vitro. In vivo experiments demonstrated that the P. divaricata extract significantly restored elevated hepatic biomarkers and protected normal hepatic architecture. The presence of rutin may explain the hepatoprotective potential of P. divaricata.