| Summary: | With the prevalence of obesity all over the world, human health has been seriously affected. In particular, the number of diabetic and cardiovascular diseases has increased dramatically. The herb <i>Coreopsis tinctoria</i> (<i>C. tinctoria</i>) shows diverse biological and pharmacological activities, which are mainly attributed to its flavonoids. However, the specific functional substances that play an active role in <i>C. tinctoria</i> remain unclear, and its mechanism has not been deeply explored. In this study, we established a diet-induced obesity (DIO) mice model and treated mice with <i>C. tinctoria</i> or kaempferol for 8 weeks. The results showed that both <i>C. tinctoria</i> and kaempferol lowered body weight, reduced fasting blood glucose, and improved glucose tolerance and insulin resistance to alleviate obesity in DIO mice. The level of hemoglobin A1c also decreased significantly after treatment with <i>C. tinctoria</i> and kaempferol. Moreover, the administration of <i>C. tinctoria</i> and kaempferol also restored gut microbiota imbalance and significantly increased <i>Desulfovibrio</i> and <i>Butyricimonas</i> levels, which have been reported to improve glucose metabolism and intestinal health. In general, our study shows that <i>C. tinctoria</i> is a potential hypoglycemic substance for obesity and may reduce blood glucose by regulating gut microbiota, and that kaempferol is one of the effective substances of <i>C. tinctoria</i>.
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