Multi-omics and experimental validation reveal the mechanism of Oenothera biennis against type 2 diabetes

The pathogenesis of type 2 diabetes (T2D) is complex. Oxidative stress has been demonstrated to be closely related to the pathogenesis of T2D. Oenothera biennis (OeB) is a type of plant exhibiting antioxidant activity. However, the effect and mechanism of OeB in treating T2D are unclear. Thus, OeB was investigated for its effect and potential mechanism in treating T2D. The chemical compounds of OeB stem extract were identified via ultra-performance liquid chromatography-mass spectrometry in series (UPLC-MS/MS). The targets of OeB were predicted via network pharmacology and molecular docking. The T2D model mice were induced via high-fat diet feeding and intraperitoneal injections of streptozotocin (STZ). The high glucose (HG) model cells were induced via the addition of 25 mmol/L glucose in MIN6 cells. The effects of OeB on T2D mice and cells were investigated by using an enzyme-linked immunosorbent assay (ELISA) and western blotting. Changes in the microbiota of colon content were measured by using 16 S rRNA sequencing. Pancreatic metabolomics was detected by using UHPLC-Q-TOF. A total of 20 active compounds, 130 common T2D targets, and 9 hub targets were predicted. In-vivo experiments revealed that the OeB stem extract significantly reduced the levels of fasting plasma glucose (FPG), Homeostasis model assessment-Insulin resistance (HOMA-IR), and malondialdehyde (MDA), improved glucose tolerance, elevated the levels of insulin (INS), superoxide dismutase (SOD), and glutathione (GSH), and increased the number and area of pancreatic islets in T2D mice ( p < 0.05). Metabolomics indicated that OeB may regulate the metabolism of choline and aspartate. OeB could reduce the abundances of Alistipes , Lachnospiraceae_UCG-006 , Lachnospiraceae_UCG-001 , and Eubacterium_nodatum_group , as well as increase the abundance of Lactobacillus , Sporosarcina , and Candidatus_Stoquefichus . Spearman correlation analysis indicated that Lachnospiraceae_UCG-001 , Eubacterium_nodatum_group , and Candidatus_Stoquefichus might be closely related to Choline and Aspartate metabolism. In-vitro experiments revealed that OeB stem extract significantly decreased the levels of proINS and MDA, but increased the levels of INS, SOD, and GSH in MIN6 cells ( p < 0.05). Moreover, OeB stem extract significantly increased the levels of p-Akt and p-GSK-3β ( p < 0.05). In conclusion, OeB stem extract might ameliorate the pathology of T2D mice by modulating the composition of microbiota in colon content and participating in the metabolism of choline, alanine, aspartate, and glutamate.