Introduction: The liver plays a crucial role in metabolic, detoxification, and endocrine functions. Hepatic wellness imbalances are driven by acute factors like hepatitis and drug allergy, and chronic ones like non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). In NAFLD, steatosis drives hepatic fibrogenesis to augment liver injury cum inflammation. Liver fibrosis is a challenging quest in hepatology in the search for safer and specific therapeutics. This study investigates the hepato-protective effect of Phyllanthus niruri compounds against liver fibrosis targets like LOXL2, HSP-47, BRD4, and IKKB, and compares their anti-hepatic fibrosis activity against known inhibitors.

Methodology: Phytochemicals from P.niruri were selected from the literature, and potential compounds which satisfy the acceptable thresholds of Mol.wt, Lipinski rule, and bioavailability were explored for in silico virtual screening. Liver fibrosis targets that influence HSC activation (BRD4), collagen stability (LOXL-2 & HSP-47), and fibrotic inflammation (IKKB) with the PDB Ids 6C7Q, 5ZE3, 3ZHA, and 3RZF, respectively, were investigated using Auto dock Vina docking software and further analysed for reliable ADMET parameters.

Results: The virtual screening reveals that compounds like β-sitosterol, cianidanol, ellagic acid, epicatechin gallate, epigallocatechin gallate, hinokinin, methyl brevifolincarboxylate, niruriflavone, phyllnirurin, 4-sinapoyl quinic acid, and quercetin showed more promising interaction with the liver fibrosis targets BRD4, LOXL-2, HSP-47, and IKKβ, in comparison to the known inhibitors like CE277, levoleucovorin, HSP47 inhibitor III, and K 252a, respectively. P.niruri compounds also qualified the permissible thresholds of ADMET.

Conclusion: Our in silico results suggest that Phyllanthus niruri compounds have the potential to be developed as an effective drug candidate towards the management of hepatic Fibrosis.