Comparative hepatoprotective and antifibrotic effects of Amaranthus spinosus (Linn.) leaf, stem, and root extracts in oxidative stress-induced murine liver fibrosis

Abstract

Liver fibrosis is a progressive pathological disease characterised by excessive deposition of extracellular matrix and damage to hepatocellular architecture. Despite increasing therapeutic requirements, existing antifibrotic therapies are limited. Amaranthus spinosus, an ethnomedicinal plant used by many tribal groups in India, exhibits antioxidant and anti-inflammatory properties; however, its antifibrotic effectiveness remains unknown. This study evaluated and compared the hepatoprotective and antifibrotic effects of A. spinosus leaf, stem, and root extracts in a thioacetamide (TAA)-induced murine model of liver fibrosis. Mice were divided into eleven groups: control, TAA, extract-alone, extract-treated (leaf, stem, and root) in the TAA group, TAA withdrawal, and vehicle groups (n = 6). The hepatoprotective effects were assessed using biochemical markers of liver function, including SGPT, SGOT, ALP, GGT, and total and direct bilirubin. Additional evaluations included histopathological examination, collagen deposition analysis using Sirius Red/Fast Green staining, and the activation of hepatic stellate cells, measured by α-smooth muscle actin (α-SMA) through immunohistochemistry. TAA treatment significantly elevated liver enzymes, collagen deposition, tissue damage, and α-SMA expression. A. spinosus root extract (ASRE) demonstrated significant enhancement in hepatic function (p < 0.01), a substantial reduction in fibrosis (p < 0.01), a notable decrease in α-SMA expression (p < 0.01), and restored hepatic architecture. Stem and leaf extracts, by contrast, showed only modest efficacy. A. spinosus root extracts show strong hepatoprotective and antifibrotic effects in TAA-induced liver injury, supporting its potential as a plant-based treatment for hepatic fibrosis.