Hepatoprotective and Anti-inflammatory Potential of Crude methanolic extract of Euphorbia pilulifera via NF-KB/Nrf2/Akt/TGF-β1 pathway

Liver fibrosis is a natural process that initiates after liver injury to repair the damaged tissue. The liver has a significant capacity for self-repair of the damaged tissue. To a great extent, the miscellaneous interactions of immune cell subtypes manage these repair procedures like fibrosis and wound healing. Objectives: To assess the hepatoprotective and anti-inflammatory potential of Euphorbia pilulifera through modulating the NF-KB/Nrf2/AKT/TGF-β1 pathway. Methods: Euphorbia pilulifera methanolic extract was primarily assessed for its cytotoxic potential against HepG2 cells. Methanolic extract of E. pilulifera showed 90% hepatoprotective activity against CCl4- induced toxicity in HepG2 cells. The methanolic extract downregulated the NF-κB gene by 90%; the AKT, gene by 14%, and the TGF-β1 gene expression by 69% at the concentration of 50µg/ml at the mRNA level. On the other hand, methanolic extract of E. pilulifera increased the expression of the Nrf2 gene by 44% at 50µg/ml concentration. Furthermore, the antioxidant activity of leaves extract through DPPH radical scavenging assay was estimated. Results: Methanolic extract showed 50.83± 0.39% inhibition against DPPH radicals at 200µg/ml concentration. In addition, the anti-inflammatory potential of the crude extract was assessed. The methanolic extract at 25µg/ml concentration revealed the maximum percentage of hemolysis protection. The methanolic extract was found highly effective against inflammation and hepatotoxicity. Conclusions: Euphorbia pilulifera leaf extract has the potential to ameliorate hepatic injury and inflammation in HepG2 cells.