Tanshinone IIA accelerates diabetic wound healing via suppression of macrophage NLRP3 inflammasome activity.

Diabetic foot ulcer (DFU) is a serious complication of diabetes involving persistent inflammation and impaired healing due to neurovascular abnormalities. Tanshinone IIA (Tan IIA) has been reported to exert anti-inflammatory, antioxidant, and vascular protective effects, with potential therapeutic benefits for diabetic complications. The study aims to investigate the therapeutic effect of Tanshinone IIA on diabetic wound healing and elucidate its underlying mechanisms, with a focus on its modulation of macrophage polarization and inhibition of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome. A rat model of full-thickness dorsal skin wound with diabetes was established, and human acute monocytic leukemia (THP-1) cells were used for in vitro validation. Results demonstrated that Tan IIA significantly accelerated wound closure, enhanced re-epithelialization, improved collagen organization, and increased angiogenesis in diabetic rats. At the mechanistic level, Tan IIA promoted the polarization of M1 macrophages toward the M2 phenotype and inhibited NLRP3 inflammasome activation in macrophages, leading to reduced secretion of interleukin-1β(IL-1β) and interleukin-18(IL-18) and alleviation of local inflammation. Consistent with in vivo findings, Tan IIA also suppressed NLRP3 inflammasome activity and decreased proinflammatory cytokine production in THP-1 cells. These results indicate that Tan IIA facilitates diabetic wound healing by modulating macrophage polarization and inhibiting NLRP3-mediated inflammatory response, suggesting its potential as a novel therapeutic agent for DFU.