Evaluation of the Hypoglycemic Mechanism of a Polyherbal Formulation by Integrating Network Pharmacology and Pharmacology Experiments

Rosa rugosa Thunb., Punica granatum L., and Cichorium glandulolsum Boiss. et Huet. are traditional herbal medicine, which can treat diabetes and diabetes complications, a formulation named RPC is composed of these three plants. The aim of this study was to investigate the chemical constituents and potential pharmacological mechanisms of RPC in treating diabetes. RPC significantly inhibited the activities of α-glycosidase and PTP1B, and has good activity of free radical scavenging. The main chemical constituents of PRC were analyzed by HPLC-QTOF-MS, a total of 45 constituents were identified. The key targets and main signaling pathways were predicted by network pharmacology. Experimental validation revealed that RPC enhanced glucose consumption and uptake while mitigating oxidative stress in L6 cells. Notably, signaling pathways such as PI3K/AKT/FoxO1, AMPK/Nrf2/HO-1, and endoplasmic reticulum stress pathways, as predicted by network pharmacology, were also markedly induced by RPC. In the animal experiment, four weeks of RPC treatment resulted in significant reductions in blood glucose and lipid profiles, along with improvements in glucose tolerance, insulin tolerance, antioxidant enzymes, and glycogen synthesis in db/db mice. The observed hypoglycemic effect of RPC may be attributable to the combined effects of signaling pathways regulating glucose metabolism, energy sensing and inhibition of oxidative stress.