Saikosaponin A Accelerates Diabetic Wound Healing by Suppressing Macrophage Pyroptosis and Activating Mitophagy

Diabetic wounds are a severe complication characterized by persistent inflammation and impaired tissue repair, often leading to chronic, non-healing ulcers. Current treatments often fall short in addressing the underlying cellular dysfunctions. Macrophage pyroptosis, a highly inflammatory form of programmed cell death, contributes significantly to this chronic inflammation, while dysfunctional mitochondrial quality control, specifically mitophagy, further exacerbates impaired healing. Saikosaponin A (SSA) is being investigated for its anti-inflammatory and cytoprotective properties, with its potential role in modulating macrophage pyroptosis and mitophagy in diabetic wound contexts remaining a critical research gap.

Researchers used streptozotocin (STZ)-induced diabetic mice with full-thickness wounds, treating them locally with Saikosaponin A (SSA). Wound repair, inflammatory responses, macrophage pyroptosis-associated signaling, and AMPK/mitophagy-related pathways were evaluated in vivo. In vitro, RAW264.7 macrophages were exposed to high glucose (HG) or an equiosmolar mannitol control. A macrophage-fibroblast co-culture system assessed fibroblast responses, and Compound C was used to investigate AMPK signaling involvement.