New Insights Into Ginseng and Clove Supplementation: Alleviating Obesity by Reducing Leptin Resistance and Reshaping the Gut Microbiota

ABSTRACT Ginseng ( Panax ginseng ) and clove ( Syzygium aromaticum ) are traditional food supplements, reputed for their broad‐spectrum health benefits. This study investigated the anti‐obesity effects and underlying mechanisms of the alcohol extract of ginseng–clove (AEGC), focusing on leptin resistance (LR) and gut microbiota remodeling. In high‐fat diet mice, AEGC significantly alleviated weight gain, normalized glucose and lipid profiles, reduced lipid accumulation, and mitigated LR. Mechanistically, AEGC can activate the JAK2/STAT3 pathway via leptin‐receptor interactions and modulate the AMPK/mTOR/SREBP pathway, thereby mitigating obesity in mice. Spectrum–effect relationship analysis identified ginsenoside Re and eugenol as primary active constituents, with molecular dynamics simulations confirming stable binding of ginsenoside Re to LR. Notably, AEGC can reshape the composition of dysregulated gut microbiota in obese mice, especially Lachnospiraceae , Bacteroidaceae , and Oscillospirales , and a strong correlation between the altered gut microbiota and LR. Penicillin‐mediated microbiota disruption blunted AEGC's anti‐obesity efficacy, confirming a microbiota‐dependent mechanism. These findings highlight the therapeutic potential of the ginseng–clove combination as a natural dietary supplement for obesity management, offering novel insights into integrative strategies targeting both host metabolism and microbial symbiosis.