Manoj AB, Anil Kumar Venkategowda KODIHALLY, Banappa UNGER, Sudeep KS, Akshay SHAMNEWADI, Shamanand MALLAPUR
Journal of Research in Pharmacy - 2026;30(1):145-159
Obesity is a global health challenge associated with diabetes, cardiovascular diseases, and certain cancers. Although FDA-approved anti-obesity drugs are available, they often cause adverse effects and weight regain upon discontinuation, highlighting the need for safer alternatives. Medicinal plants such as Euphorbia hirta L., traditionally used for various therapeutic purposes and may aid in obesity management. This study evaluated the effects of Euphorbia hirta L. on metabolic rate regulation and lipid accumulation in high-fat diet (HFD) -fed zebrafish larvae. The potential mechanisms of action and key phytoconstituents were predicted through in silico network pharmacology and molecular docking studies. Zebrafish larvae at 4 days postfertilization were divided into three groups (n = 30 each): a naive control group (standard diet), an HFD control group (0.1% egg yolk-supplemented diet), and treatment groups receiving three concentrations of Euphorbia hirta ethanolic extract and its fractions from day 4 to day 6. In vivo studies assessed lipid accumulation via Oil Red O staining and metabolic rate via resazurin assay. Among 42 identified phytoconstituents, kaempferol-3-O-rhamnoside, beta-sitosterol, trans-5-O-(4-coumaroyl)-D-quinic acid, and 1-(2-piperidin-4-ylethyl) pyrrolidin-2-one, showed strong binding to obesity-related targets (mTOR, STAT3, ACACA, ESR1, and TLR4) with binding energies ranging from -6.1 to -8.9 kcal/mol. LC-MS confirmed their presence in the ethanolic extract and ethyl acetate fraction. In vivo study revealed treatment with Euphorbia hirta L. ethanolic extract and ethyl acetate fraction significantly reduced lipid accumulation (***p < 0.001 vs. HFD control) and improved metabolic rate in a time- and dose-dependent manner (***p < 0.001), compared to HFD-control. These findings suggest that Euphorbia hirta L. exerts anti-obesity effects by modulating lipid metabolism and enhancing energy expenditure, providing a scientific basis for its potential development as a multi-targeted therapeutic agent.
