AREEBA IMTIAZ, SYED MUHAMMAD ALI SHAH, SULTAN AYAZ

DOI: https://doi.org/

Background: Liver fibrosis, characterized by the excessive deposition of extracellular matrix proteins predominantly collagen, causes distortion of architecture and poor liver functioning. Existing anti-fibrotic treatment approaches are insufficient, and there is a need to investigate natural phytochemicals with hepatoprotective and regenerative effects.

Aims & Objectives: Aim was to evaluate hepatoprotective and anti-fibrotic properties of extracts of Euphorbia hirta and Lepidium sativum and their active phytochemicals, Kaempferol and Coumestrol, with CCL4-induced hepatic fibrosis in rats.

Methodology: Combined in silico and in vivo method was used. Kaempferol and Coumestrol were identified as lead compounds in molecular docking of 69 phytochemicals against IL-6, AKT1, EGFR, and Caspase-3. Sixty-four male albino rats were stratified into control, intoxicated, standard drug, and treatment groups, administered with plant extracts and phytochemicals (50 and 100 mg/kg), and liver function tests, hematological parameters, and histopathology were evaluated.

Results: Histopathological results showed high-dose of Kaempferol and Coumestrol exhibited hepatic architecture restoration with no necrosis, hemorrhage, and fatty changes. Biochemical analysis showed improvement in liver functioning in all treatment groups, with decrease in levels of ALT, AST, ALP, and bilirubin compared to the intoxicated group. Hematologic outcomes revealed dose-related normalization of RBCs, hemoglobin, platelets, and WBCs with L. sativum extract. Overall, Coumestrol showed highest hepatoprotective effect, followed by Kaempferol, both had higher hepatoprotective effect than plant extracts.

Conclusion: Kaempferol and Coumestrol demonstrated significant hepatoprotective and anti-fibrotic properties, making these important as cost-effective alternative natural therapies against liver fibrosis.