Polyphenol Fraction of<i> Cyclocarya</i><i> Paliurus</i> Leaves Modulates Intestinal Microbiota and Alleviates Type 2 Diabetes Mellitus in Mice

Background: Type 2 diabetes mellitus has become a serious social concern, and diet-based therapies, such as those involving the Cyclocarya paliurus leave tea are gaining attention for preventing and alleviating diabetes mellitus. The objective of the present study was to determine the active components of this tea and understand the associated mechanism. Methods: The active fraction of C. paliurus was traced using the Cell Counting Kit -8 in response to streptozotocin-induced cell damage, and its components were identified using ultra-performance liquid chromatography coupled with quadrupole time-offlight mass spectrometry. Flow cytometry and western blotting were performed to examine the effects of the active fraction on streptozotocin-induced pancreatic beta cell damage. A high-fat diet combined with streptozotocin-induced animal model was used to identify the effects of this extract against type 2 diabetes mellitus following 8 weeks of gavage administration. Results: The polyphenol fraction of C. paliurus protected against streptozotocin-induced cell damage and up-regulated cleaved caspase-3 and the Bax/Bcl-2 ratio in pancreatic beta cells (p < 0.05). Moreover, this administration of the extract effectively reduced body weight, blood glucose level, and increased insulin sensitivity (p < 0.05). The treatment also alerted the abundance of gut microbiota, particularly by upregulating the abundance of Akkermansia and decreasing pathogenic bacteria genus Helicobacter (p < 0.05). Conclusions: Our findings suggested that the polyphenol fraction of C. paliurus could be a potential candidate for gut microbiota modulation as a dietary component for the prevention or management of type 2 diabetes mellitus.