Formononetin Promotes Pressure Ulcer Healing through Coordinated Regulation of NF-κB and PI3K-Akt Signaling Pathways

Pressure ulcers (PUs) represent a significant clinical challenge in immobilized patients and the aging population, characterized by persistent inflammation, impaired tissue regeneration, and dysregulated healing processes. In this study, we systematically investigated the therapeutic potential of formononetin (FMN) extracted from traditional Chinese medicine in preventing and treating PUs. Experimental results from the magnetically induced ischemia-reperfusion PUs rat model demonstrated that FMN intervention accelerated wound healing rates, with a clear dose-response relationship observed. Histopathological examination (H&E staining) revealed substantial improvements in tissue architecture, including enhanced epidermal integrity and reduced inflammatory infiltration. Moreover, the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the wound tissue was reduced. FMN inhibited apoptosis by down-regulating the expression of cleaved caspase-3 and Bax in pressure ulcer tissues and up-regulating the expression of Bcl-2. In addition, FMN promotes collagen deposition and expression of α-SMA and collagen I in wound tissue, thereby improving tissue remodeling. Integrated bioinformatic and Western blot validation identified simultaneous regulation of NF-κB and PI3K-Akt pathways as the core mechanism. These results reveal that FMN may facilitate PUs healing through dual mechanisms, suppressing inflammation and apoptosis via NF-κB inhibition, and promoting cell survival and tissue repair via PI3K-Akt activation. This suggests that FMN has the potential to be a drug for the preventive and therapeutic effects of PUs and lays the foundation for the clinical development of FMN-based treatment options.