Cinnamaldehyde-surfactin nano-capsulation mitigates high-fat diet/ streptozotocin-induced diabetes and modulate gut microbial dysbiosis

Type 2 diabetes mellitus (T2DM) is associated with liver dysfunction and intestinal dysbiosis. Cinnamaldehyde have been reported to ameliorate T2DM, on the other hand, its mechanism is unclear. In the present study, surfactin-loaded cinnamaldehyde microemulsion (Cin-NEs) supplementation significantly promoted glucose uptake in insulin resistant HepG2 cells. According to further research, Cin-NEs treatment dramatically upregulated phosphorylated-phosphoinositide-3 kinase (p-PI3K) and phosphorylated-protein kinase B (PKB/Akt), downregulated phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6pase), these further enhance hepatic glycogen synthesis and suppress gluconeogenesis to promote glucose uptake. Cin-NEs supplementation lowered fasting blood glucose (FBG) by 34.29-41.43% and insulin resistance (IR) by 36.0-40.0%, increased glucose tolerance by 49.33-53.33% compared with those in the T2DM group, reduced liver’s lipid accumulation and inflammation in mice with T2DM induced by a high-fat diet (HFD) and streptozotocin (STZ). A Cin-NEs administration reduced Prevotella and Shigella , while increased Akkermansia genus and colonic tight junction protein Claudin-1, ZO-1 and Occludin. Furthermore, Cin-NEs also improved hepatic glucose metabolism by activating the adenosine monophosphate-activated protein kinase (AMPK) and PI3K/Akt signaling pathway, downregulating PEPCK and G6Pase protein, and upregulating GLUT4 and GS protein levels. All of these findings revealed that Cin-NEs not only ameliorated HFD/STZ-induced glucose metabolism disorder but also reversed gut dysbiosis and preserved intestinal barrier integrity in T2DM mice. Cinnamaldehyde exhibits a similar effect to Cin-NEs, and the effect of Cin-NEs with 10 mg/kg·BW is equal to that of cinnamaldehyde with 20 mg/kg·BW. All data reveals that cinnamaldehyde-surfactin nano-capsulation possesses high stability in vivo and bioavailability to mitigates T2DM in mice.