Integrating serum pharmacochemistry and network pharmacology to reveal the mechanism of chickpea in improving insulin resistance

Although chickpea have great potential in the treatment of obesity and diabetes, the bioactive components and therapeutic targets of chickpea to prevent insulin resistance (IR) are still unclear. The purpose of this study was to investigate the chemical and pharmacological characteristics of chickpea on IR through serum pharmacochemistry and network pharmacology. The results revealed that compared with other polar fractions, the ethyl acetate extract of chickpea (CE) had the definitive performance on enhancing the capacities of glucose consumption and glycogen synthesis. In addition, we analyzed the components of CE in vivo and in vitro based on UPLC-Q-Orbitrap HRMS technology. There were 28 kinds of in vitro chemical components, among which the isoflavones included biochanin A, formononetin, ononin, sissotrin, and astragalin, etc. Concerningly, the chief prototype components of CE absorbed into the blood were biochanin A, formononetin, loliolide, and lenticin, etc. Furthermore, a total of 209 common targets between IR and active components of CE were screened out by network pharmacology, among which the key targets involved PI3K p85, NF-κB p65 and estrogen receptor 1, etc. Specifically, KEGG pathway analysis indicated that PI3K-AKT signaling pathway, HIF-1 signaling pathway, and AGE-RAGE signaling pathway may play critical roles in the IR remission by CE. Finally, the in vitro validation experiments disclosed that CE significantly balanced the oxidative stress state of IR-HepG2 cells and inhibited expressions of inflammatory cytokines. In conclusion, the present study will be an important reference for clarifying the pharmacodynamic substance basis and underlying mechanism of chickpea to alleviate IR.