Saikosaponin A promotes diabetic wound healing by suppressing NLRP3 inflammasome-associated macrophage pyroptosis and modulating mitophagy-related signaling.

Authors

Yun Pan, Cui Zhou, Jing Xu, Yang Han, Xiaoli Chen, Xiangkang Jiang, Aijun Chen

Published in

Molecular biology reports. Volume 53. Issue 1. Oct 25, 2026. Epub Oct 25, 2026.

Abstract

Diabetic wounds are characterized by persistent inflammation and impaired tissue repair. Saikosaponin A (SSA) exhibits anti-inflammatory and cytoprotective activities, but its effects on macrophage pyroptosis and mitophagy-related signaling during diabetic wound healing remain unclear.
In vivo, streptozotocin (STZ)-induced diabetic mice with full-thickness wounds were treated locally with SSA, and wound repair, inflammatory responses, macrophage pyroptosis-associated signaling, and AMPK/mitophagy-related pathways were evaluated. In vitro, RAW264.7 macrophages were exposed to high glucose (HG), with an equiosmolar mannitol control, and a macrophage-fibroblast co-culture system was used to assess fibroblast responses. Compound C was used to investigate the involvement of AMPK signaling.
Diabetic mice exhibited delayed wound healing, enhanced GSDMD-associated signaling, and increased local and systemic inflammation. HG increased GSDMD cleavage, PI positivity, LDH release, and IL-1β/IL-18 secretion, whereas the mannitol control did not reproduce these changes. Fibroblasts co-cultured with HG-exposed macrophages showed increased P53/P21 expression, reduced EdU incorporation, and impaired migration. SSA accelerated wound closure, improved tissue remodeling, and reduced NLRP3/caspase1/GSDMD-associated inflammatory responses. SSA also increased AMPK phosphorylation and PINK1/Parkin- and LC3-related signaling while reducing P62 accumulation. Compound C attenuated these SSA-associated changes.
SSA promotes diabetic wound repair and is associated with activation of AMPK/mitophagy-related signaling and suppression of NLRP3/GSDMD-associated macrophage pyroptotic responses.

PMID:
42927588
Bibliographic data and abstract were imported from PubMed on 26 Oct 2026.

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