Methanolic extracts of Amaranthus spinosus (Linn.) mitigate TAA-Induced hepatic fibrosis through modulation of inflammatory cytokines and profibrotic signalling.
TL;DR
The root extract of A. spinosus shows strong therapeutic potential as a multi-target agent capable of disrupting the inflammation-fibrosis axis in chronic liver injury, and is demonstrated to exert potent antifibrotic activity by modulating hepatocyte-driven cytokine networks and suppressing redox-sensitive inflammatory pathways.
Abstract
Background
Persistent oxidative stress disrupts intrahepatic immune homeostasis, leading to cytokine dysregulation and fibrogenic progression in the liver. This study investigated the immunomodulatory and antifibrotic effects of methanolic extracts of Amaranthus spinosus (leaf, stem, and root) in a thioacetamide (TAA)-induced murine model of hepatic fibrosis.
Methods
Swiss albino mice were administered TAA (150 mg/kg, intraperitoneally, thrice weekly for 8 weeks) to induce fibrosis, followed by oral treatment with plant extracts (250 mg/kg) for 15 consecutive days. Hepatocyte-specific cytokine expression (IL-6, TNF-α, IL-12, TGF-β, and IL-10) was evaluated by flow cytometry and quantitative real-time PCR, and immunohistochemistry was used to assess COX-2 and iNOS expression.
Results
TAA administration resulted in significant upregulation of pro-inflammatory (IL-6, TNF-α, IL-12) and profibrotic (TGF-β) cytokines, along with elevated IL-10 expression, indicating dysregulated immune homeostasis. Extract treatment significantly attenuated (p < 0.01) these alterations in a fraction-dependent manner, with the root extract exhibiting the highest efficacy, restoring cytokine levels to near physiological baseline. These findings were corroborated at the transcriptional level by qPCR. Additionally, extract-treated groups showed significant downregulation of COX-2 and iNOS expression, reflecting reduced oxidative and nitrosative stress. In contrast, TAA withdrawal alone, or in combination with the vehicle control, failed to effectively normalize inflammatory markers.
Conclusions
Collectively, these results demonstrate that A. spinosus exerts potent antifibrotic activity by modulating hepatocyte-driven cytokine networks and suppressing redox-sensitive inflammatory pathways. The root extract, in particular, shows strong therapeutic potential as a multi-target agent capable of disrupting the inflammation-fibrosis axis in chronic liver injury.