Enhanced Anti-Obesity Effects of Euphorbia Kansui Extract through Macrophage and Gut Microbiota Modulation: A Real-World Clinical and In Vivo Study

Rising obesity and associated multi-systemic complications amplify the health burden. Euphorbia kansui (EK) extract is clinically recognized for managing obesity. In a human study, 240 obese individuals were categorized into two cohorts: those receiving solely herbal medicine (HM group) and those administered EK concomitantly with herbal medicine (EK group). An in vivo examination using C57BL/6-Lep^ob/Lep^ob mice elucidated mechanisms involving macrophages and gut microbiota with associated metabolic advantages. The clinical study revealed a significant 7.22% body weight reduction during 91.55 average treatment days and examined 16.71% weight loss at 300 days after treatment. In whole subjects, 60.4%, 21.3%, and 6.3% achieved weight reductions exceeding 5%, 10%, and 15%, respectively. Impressively, the EK group exhibited superior weight loss compared to the HM group (EK: -7.73% vs. HM: -6.27%, p = 0.012). The anti-obesity effect was positively associated with EK therapy frequency and herbal medicine duration. In the in vivo study, EK significantly improved insulin sensitivity and mitigated infiltration of adipose tissue macrophages (ATMs) by modulating the CD11c+ and CD206+ subtypes. EK also correlated with increased Bacteroidetes and Firmicutes populations and reduced Proteobacteria and Verrucomicrobia. Consequently, EK is an effective adjunctive anti-obesity therapy offering metabolic benefits by modulating ATMs and gut microbiota profiles.