Therapeutic mechanisms of mulberry leaves in type 2 diabetes based on metabolomics

Background: Type 2 diabetes (T2D) is considered as one of the most significant metabolic syndromes worldwide, and the long-term use of the drugs already on the market for T2D often gives rise to some side effects. The mulberry leaf (ML), Morus alba L., has advantages in terms of its comprehensive therapeutic efficacy, which are characterized as multicomponent, multitarget, multipathway, and matching with the complex pathological mechanisms of diabetes. Methods: T2D rats were established by a high-fat diet combined with an intraperitoneal injection of streptozotocin; an evaluation of the hypoglycemic effects of the ML in combination with fasting blood glucose and other indicators, in addition to the utilization of metabolomics technology, was performed to analysis the metabolite changes in serum of rats. Results: MLs significantly reduced the fasting blood glucose of T2D rats, while improving the symptoms of polyphagia and polyuria. ML treatment altered the levels of various metabolites in the serum of T2D rats, which are involved in multiple metabolic pathways (amino acid metabolism, carbohydrate metabolism, and lipid metabolism), played a role in antioxidative stress and anti-inflammation, modulated immune and gluconeogenesis processes, and improved obesity as well as insulin resistance (IR). Conclusion: The ML contains a variety of chemical components, and metabolomic results have shown that MLs regulate multiple metabolic pathways to exert hypoglycemic effects, suggesting that MLs may have great promise in the development of new hypoglycemic drugs.