Anti-diabetic potential of Artemisia monosperma Delile extract related to anti-inflammatory, antioxidant, and wound-healing properties.

Artemisia monosperma Delile (Asteraceae) is traditionally used for gastrointestinal issues and diabetes. This study aimed to characterize its phenolic profile and evaluate the molecular basis for its antioxidant, anti-inflammatory, and antidiabetic properties. The defatted 80% aqueous methanol extract (DAME) of A. monosperma aerial parts was profiled by HPLC-HRMS to identify phenolic compounds. Antihyperglycemic activity was tested via the Sucrose Loading Model (SLM) and a Type 2 diabetes model. Anti-inflammatory effects were measured in LPS-stimulated RAW264.7 cells by TNF-α and CRP gene expression. Wound-healing potential was evaluated in BJ cells, and antioxidant activity was assessed against superoxide, DPPH, and NO radicals. Molecular docking was used to examine the binding of the identified metabolites to targets, including inducible nitric oxide synthase (iNOS) and sulfonylurea receptor 1 (SUR1). The HRHPLC/MS analysis of the DAME of A. monosperma tentatively identified 25 secondary metabolites in the negative mode, including twelve phenolic acid derivatives, eight flavonoid compounds, and five miscellaneous terpenes. The DAME exhibits potent antihyperglycemic activity, with a 300 mg% dose reducing blood glucose levels by approximately 26% in a Type 2 diabetes model, comparable to diamicron. It also shows strong anti-inflammatory effects, reducing TNF-α and CRP gene expression by 66% and 82%, respectively, in LPS-stimulated RAW264.7 cells. Furthermore, it enhances wound healing, achieving approximately 79% closure in treated BJ cells compared to 58% in controls, and exhibits antioxidant activity. The identified library of compounds 1-25 was virtually screened against (iNOS) and (SUR1) to assess their binding affinities for each target. The binding modes of the compounds with the lowest energy scores for each were investigated. Different compounds demonstrated stronger affinities to each target than the co-crystallized ligand, among which compounds 4, 9, 11, and 14 possessed the lowest binding energies to both. A. monosperma DAME contains a variety of phenolic compounds and shows a potent multi-functional agent possessing anti-diabetic, anti-inflammatory, wound healing, and antioxidant activities, suggesting its therapeutic potential. However, more research is necessary to confirm its safety for clinical application.