Rutin Promotes Wound Healing by Inhibiting Oxidative Stress and Inflammation in Metformin-Controlled Diabetes in Rats

Diabetes mellitus (DM) is a metabolic disorder with a notable increase in global incidence in recent years. Individuals diagnosed with diabetes are at an elevated risk of morbidity and mortality compared with the general population. For several years, the potential of phytochemicals as anti-inflammatory agents to improve the healing of diabetic wounds has been under investigation. Rutin, a flavonoid, is a particularly promising candidate for use in wound healing. Our study aims to investigate the potential impact of a topical application of rutin nanoformulation on wound healing in streptozotocin (STZ)-induced hyperglycemic rats controlled with metformin, with a focus on its anti-inflammatory and antioxidant properties. Rats are randomized into 3 groups. GI: diabetic control group; wound untreated. GII: diabetes and rutin-NP-treated wound. GIII: diabetic + β-sitosterol-treated wound. The findings suggest that topical application of rutin-NPs has the potential to enhance the wound-healing process by attenuating oxidative stress, as evidenced by restoring GSH, CAT, and SOD antioxidants, and decreasing MDA production mediated by Nrf2 activation. Also, inflammation is suppressed, as indicated by the decreased CRP, IL-1β, IL-6, and TNF-α levels. Molecular docking data confirm the biological data of rutin, where rutin is docked into the catalytic site of the X-ray crystallographic structures of CRP, Keap-1, IL-1β, IL-6, and TNF-α via grid-based ligand docking. The binding affinity and binding energy of ligand-protein interactions demonstrate the affinity and binding to the specifically selected proteins.