Polymethoxyflavone–Enriched Fraction from Ougan (Citrus reticulata cv. Suavissima) Attenuated Diabetes and Modulated Gut Microbiota in Diabetic KK-A^y Mice

Diabetes mellitus is a serious, chronic disease worldwide; yet it is largely preventable through physical activity and healthy diets. Ougan (Citrus reticulata cv. Suavissima) is a characteristic citrus variety rich in polymethoxyflavones. In the present study, the anti-diabetic effects of the polymethoxyflavone-enriched fraction from Ougan (OG-PMFs) were investigated. Diabetic KK-Ay mice were supplemented with different doses of OG-PMFs for 5 weeks. Our results demonstrated that OG-PMFs exhibited robust protective effects against diabetes symptoms in KK-Ay mice. The potential mechanisms may partially be attributed to the restoration of hepatic GLUT2 and catalase expression. Notably, OG-PMF administration significantly altered the gut microbiota composition in diabetic KK-Ay, indicated by the suppression of metabolic disease-associated genera Desulfovibrio, Lachnoclostridium, Enterorhabdus, and Ralstonia, implying that the gut microbiota might be another target for OG-PMFs to show effects. Taken together, our results provided a supplementation for the metabolic-protective effects of PMFs and highlighted that OG-PMFs hold great potential to be developed as a functional food ingredient.