Hepatoprotective efficacy of Argemone mexicana L. root in paracetamol-induced hepatotoxicity in a rat model

Ethnopharmacological relevance: Argemone mexicana L. (Papaveraceae), a weed that thrives in the tropical and subtropical areas of South and Central America, Mexico, Caribbean Islands and India. In India, it has been used traditionally to treat vesicular calculus, inflammatory conditions, and hepatobiliary disorders.

Aim of the study: The present study was aimed to investigate the hepatoprotective efficacy of A. Mexicana roots in paracetamol (PCM)-induced toxicity rat.

Materials and methods: The methanol extract of A. mexicana (MEAM) root was analyzed using Gas Chromatography-Mass Spectrometry (GC-MS) analysis to identify its compounds. Molecular docking analysis of the compounds was conducted against TGF-β and PPAR-α. The hepatoprotective activity of MEAM (200, 400 mg/kg) was evaluated in PCM (3000 mg/kg) intoxicated rats by measuring serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin (TB), total protein (TP), albumin (ALB), globulin (GLB), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Silymarin (100 mg/kg) was used as reference drug. Oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and lipid peroxidation (LPO) were investigated using liver homogenate. Additionally, the levels of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) were studied. The results of the study were supported by histopathological examination.

Results: GC-MS analysis revealed 163 compounds, from which eleven compounds were selected based on their docking scores against TGF-β and PPAR-α. MEAM (400 mg/kg) demonstrated a remarkable reduction in ALT, AST, ALP, GGT, and LDH in contrast to the PCM intoxicated group. A remarkable decline in TB and GLB, along with an increase in TP and ALB, was observed in the MEAM (400 mg/kg) group compared to the untreated PCM group. Rats receiving MEAM (400 mg/kg) exhibited a noticeable decrease in TC, TG, and LDL-C, along with an increase in HDL-C levels compared to PCM-induced untreated rats. The higher dose of MEAM also resulted in a significant decrease in TNF-α, IL-1β, and IL-6, and an increase in IL-4 and IL-10. Similarly, a notable elevation in SOD, CAT, and GSH, along with a decrease in MDA content, was observed in the group receiving MEAM (400 mg/kg). The histopathological result showed reduction of sinusoidal space and vesicular nuclei, with improvement of hepatocytes at the dose of MEAM (400 mg/kg). In molecular docking study, Eupatilin exhibited the highest docking scores of -10.4 kcal/mol and -9.1 kcal/mol against TGF-β and PPAR-α, respectively.

Conclusions: MEAM root at dose of 400 mg/kg exhibited hepatoprotective effect against PCM-induced toxicity rat. Eupatilin might be considered as a potential candidate for the hepatoprotective effect of A. mexicana root.