Phyllanthin Regulates Expression of NFKB/PI3K/AKT Pathway and Improves Liver Histology in Animal Model of NAFLD: A Preliminary Study

Background and Aim: Pharmacological treatment of nonalcoholic fatty liver disease (NAFLD) is still evolving. Mechanism of protection of liver injury by Phyllanthin is not clear. Dysregulation of PI3K/AKT pathway contributes to the development of non-alcoholic fatty liver disease (NAFLD). Aim of the study was to evaluate if hepatoprotective effectof Phyllanthin improving the liver histology in mice model of NAFLDis related to the regulation of NFKB/PI3K/AKTpathway. Methodology: Control male C57BL/6 mice were given normal chow diet (group A). Group B mice were fed methionine-choline deficient diet (MCDD) for 4 weeks to make NAFLD model. Control as well as MCDD mice were administered plant crude extract of Phyllanthus niruri(200 mg/kg) (group C and group D). Control and MCDD mice were also administered commercially available Phyllanthin (2mg/kg) (group E and group F). Real time PCR expression of NF-KB, AKT, PI3K and IRS-1 genes was studied and relative expression was calculated using 2ˆ-ΔΔCt method. C57BL/6 mice in all groups were dissected and evaluated for improvement in NAFLD activity score (NAS). Data was analyzed using one-way ANOVA. Results: Crude plantextract of phyllanthin(group D) significantly down regulated expression of AKT (0.90±0.17 vs. 5.89±2.63; P<0.0001), NF-KB (0.84±0.29 vs. 4.78±2.04; P<0.0001), PI3K (0.69±0.25 vs. 2.20±1.07; P<0.0001) and IRS (1.41±1.08 vs. 4.63±2.36; P=0.003) in comparison to group B (MCDD mice without plant extract). Commercially available phyllanthin (group F) also significantly downregulated expression ofAKT (1.04±0.39 vs. 5.89±2.63; P<0.0001), NF-KB (0.99±0.45 vs. 4.78±2.04; P<0.0001), PI3K (0.78±0.36 vs. 2.20±1.07; P=0.001) and IRS (1.69±2.09 vs. 4.63±2.36; P=0.015) in comparison to group B. Both crude extract and commercial phyllanthin significantly improved NAS in comparison to control MCDD mice not given phyllanthin(P=0.001). Conclusion: Improvement in liver histology with crude and commercial Phyllanthin in a mice model of NAFLD is related to the regulation of NFKB/PI3K/AKTpathway.