Investigating the protective effects of luteolin and gallic acid from Luffa acutangulavar. amara (Roxb.) C. B. Clarke. Fruit pericarp against alcohol-induced liver toxicity: Extraction, bioactivity-guided fractionation, molecular docking, and dynamics studies

Abstract

Ethnopharmacological relevance: Luffa acutangula var. amara (Roxb.) C.B. Clarke, known as 'Katu Koshataki' in Ayurveda, is a traditional medicinal plant in India. The juice of these fruits is recommended for chronic alcohol-induced liver diseases.

Aim of the study: This study aimed to validate the hepatoprotective and antioxidant properties of Luffa acutangula var. amara fruit pericarp ethanolic extract (EOLA) against ethanol-induced chronic hepatotoxicity in rats, isolate bioactive phytochemicals and in silico evaluation.

Materials and methods: Ethanolic extract of L. acutangula var. amara fruit pericarp was evaluated in chronic alcohol-induced hepatitis (20% ethanol orally twice daily for 28 days) at doses of 100 and 200 mg/kg p.o. Additionally, in vivo anti-inflammatory and antioxidant potential were assessed. Luteolin and gallic acid were isolated using bioactivity guided fractionation. Furthermore, these phytochemicals were assessed for hepatoprotective potential using molecular docking and molecular dynamics studies against different targets.

Results: The EOLA demonstrated efficacy in stabilizing elevated biochemical markers and antioxidant levels associated with ethanol-induced hepatotoxicity in rats, and it preserved the normal architecture of hepatocytes in histological analyses compared to the ethanol control group. The EOLA was subjected to fractionation using hexane: chloroform (8:2 → 2:8), followed by chloroform: methanol (8:2 → 2:8) to yield a total eight fractions. The fractions 1, 2, and 3 showed potent antioxidant potential, yielding luteolin and gallic acid as LAC-1 and LAC-3 from fractions 1 and 8, respectively. Gallic acid and luteolin were investigated using molecular docking and molecular dynamic simulation techniques to assess their interactions with key proteins such as Cytochrome P450 2C9, Superoxide Dismutase, Glutathione Peroxidase, Glutathione S-Transferase, Catalase, Peroxisome Proliferator-Activated Receptor-ϒ, Vanin-1, and Cannabinoid Receptor CB2. The metabolites exhibit strong binding stability, with a root mean square deviation range of less than 2.8 Å.

Conclusions: It can be concluded that the fruit pericarp of L. acutangula var. amara could be used as a functional food for reducing the liver damage caused by alcohol and other factors.

Keywords: Antioxidant; Gallic acid; Hepatoprotective; Luffa acutangula var. amara; Luteolin; Molecular docking; Molecular dynamic simulations.