The aim of this study was to evaluate the
therapeutic effects of Bletilla striata
polysaccharide (BSP) on wound healing in
diabetes mellitus (DM) and to explore the underlying mechanisms. DM mouse models were induced by high fat-diet feeding combined with low-dose
streptozocin injection. To establish
diabetic foot ulcer (DFU) models, DM mice were wounded on the dorsal surface. Subsequently, mice were treated with vehicle or BSP for 12 days and wound healing was monitored. The effects of BSP on the production of interleukin-1β (IL-1β),
tumor necrosis factor-α, macrophages infiltration, angiogenesis, the activation of
nucleotide-binding and oligomerization (NACHT) domain,
leucine-rich repeat (LRR), and pyrin domain (PYD)-containing
protein 3 (NLRP3)
inflammasome, and
insulin sensitivity in
wound tissues were subsequently evaluated. Separated- and cultured- bone marrow-derived macrophages (BMDMs) and cardiac microvascular endothelial cells (CMECs) were isolated from mice and used to investigate the effects of BSP on cell viability,
reactive oxygen species (ROS) generation, NLRP3
inflammasome activation and
insulin sensitivity in vitro following exposure to high
glucose (HG). BSP administration accelerated diabetic wound healing, suppressed macrophage infiltration, promoted angiogenesis, suppressed NLRP3
inflammasome activation, decreased IL-1β secretion, and improved
insulin sensitivity in
wound tissues in DM mice. In vitro, co-treatment with BSP protected against HG-induced ROS generation, NLRP3
inflammasome activation, and IL-1β secretion in BMDMs, and improved cell viability and decreased ROS levels in CMECs. Moreover, in HG exposed BMDMs-CMECs cultures, BSP treatment suppressed NLRP3
inflammasome activation and IL-1β secretion in BMDMs, and improved cell viability and
insulin sensitivity in CMECs. Furthermore, treatment with IL-1β almost completely suppressed the beneficial effects of BSP on the NLRP3
inflammasome, IL-1β secretion, and
insulin sensitivity in HG-treated BMDMs-CMECs. BSP promotes DFU healing through inhibition of the HG-activated NLRP3
inflammasome.