Investigating the Phytochemistry and Underlying Glycemic Control Mechanisms of Litchi chinensis Sonn. (Litchi) Peel Ethyl Acetate Extract in a Fructose/Streptozotocin Diabetic Model of Rats

The glycemic control potential and flavonoid profile of litchi have been documented for its hydroalcoholic extracts, while there is scarce information regarding its ethyl acetate extract. This study investigated the flavonoid profile, as well as the ameliorative potential and possible underlying mechanisms of litchi peel ethyl acetate extract on type 2 diabetes-related pathologies in a fructose/streptozotocin (STZ) model of diabetic rats. Sprague Dawley rats were induced with diabetes by administering 10% fructose for 2 weeks and a single i.p. injection of low-dose (40 mg/kg bw) STZ. Thereafter, the animals were orally administered with a low-dose (150 mg/kg bw) and high-dose (300 mg/kg bw) of the peel extract (LDPE and HDPE, respectively) and metformin (200 mg/kg bw). Compared to untreated diabetic rats (AUC = 1004 mg.h/dL), the HDPE significantly (<i>p</i> < 0.05) improved glucose tolerance (AUC = 847 mg.h/dL), which was statistically comparable (<i>p</i> ˃ 0.05) to the effect of metformin (AUC = 903 mg.h/dL). Serum insulin and pancreatic histology data showed that the STZ-induced pancreatic damage and insulin depletion was improved by the HDPE, which could be linked to the observed ameliorative effect of the extract on pancreatic lipid peroxidation and SOD and catalase activity. The extract further improved liver and muscle glycogen storage, as well as muscle hexokinase activity and Akt phosphorylation, suggesting that the extract exerts glycemic control by enhancing glycogen storage and modulating insulin-mediated signaling of glucose uptake and utilization. LC-MS data and documented reports suggest that flavonoids, such as epicatechin, cinnamtannin B2, procyanidin B5, and proanthocyanidin A2, are the possible influencing compounds. The ethyl acetate extract of litchi peel could be a source of bioactive flavonoids that can potentiate glycemic control in diabetes and mitigate oxidative stress-related pathologies.