Bletilla striata Polysaccharide Promotes Diabetic Wound Healing Through Inhibition of the NLRP3 Inflammasome

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-1 beta (IL-1 beta), tumor necrosis factor-alpha, 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-1 beta 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-1 beta 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-1 beta secretion in BMDMs, and improved cell viability and insulin sensitivity in CMECs. Furthermore, treatment with IL-1 beta almost completely suppressed the beneficial effects of BSP on the NLRP3 inflammasome, IL-1 beta secretion, and insulin sensitivity in HG-treated BMDMs-CMECs. BSP promotes DFU healing through inhibition of the HG-activated NLRP3 inflammasome.

Automated summary

Bletilla striata polysaccharide accelerates diabetic wound healing, suppresses macrophage infiltration, promotes angiogenesis, inhibits NLRP3 inflammasome activation, and improves insulin sensitivity in wound tissues in diabetic mice. It also protects against high glucose-induced ROS generation and NLRP3 inflammasome activation in vitro, while improving cell viability and insulin sensitivity.