Comprehensive amelioration of glucose and lipid metabolism dysregulation in T2DM by a Lycium blend

Objective: This study formulated a whole-plant Lycium blend (LB) to examine its effects and underlying mechanisms in ameliorating Type 2 Diabetes Mellitus (T2DM), aiming to develop safe, multi-targeted therapeutic agents.

Materials and methods: UPLC-MS/MS was used to identify the chemical constituents in LB and the bioavailable components in drug-containing serum. The therapeutic effects of LB were evaluated through in vitro and in vivo experiments using an Insulin resistance model in HepG2 cells and a T2DM mouse model. Additionally, network pharmacology was employed to analyze targets associated with blood components and elucidate the primary molecular mechanisms by which LB improves T2DM. Western blot analysis was utilized to detect protein expression in relevant signaling pathways.

Results: UPLC-MS/MS identified 22 compounds in LB, while drug-containing serum contained 9 bioavailable active components, primarily Flavonoids, organic acids, and glycosides. Without affecting food intake or body weight, in vitro and in vivo studies revealed that LB reduces Insulin resistance in HepG2 cells, improves lipid metabolism, decreases hepatic steatosis and adipocyte hypertrophy, and dose-dependently lowers daytime blood glucose levels as well as the area under the oral glucose tolerance test (OGTT) curve in T2DM mice. According to Western blot results, LB regulates glucose and lipid metabolism balance by activating the IRS1/PI3K/Akt signaling axis and the AMPK/GLUT4 pathway, suppressing NF-κB-mediated inflammatory responses, and upregulating the expression levels of PGC1α and PPARγ.

Conclusions: This study provides preclinical experimental evidence endorsing the utilization of LB as a natural functional component for the prevention and supplementary treatment of T2DM.