PMID- 33981238 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210514 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 12 DP - 2021 TI - Bletilla striata Polysaccharide Promotes Diabetic Wound Healing Through Inhibition of the NLRP3 Inflammasome. PG - 659215 LID - 10.3389/fphar.2021.659215 [doi] LID - 659215 AB - 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-1beta (IL-1beta), 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-1beta 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-1beta 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-1beta secretion in BMDMs, and improved cell viability and insulin sensitivity in CMECs. Furthermore, treatment with IL-1beta almost completely suppressed the beneficial effects of BSP on the NLRP3 inflammasome, IL-1beta secretion, and insulin sensitivity in HG-treated BMDMs-CMECs. BSP promotes DFU healing through inhibition of the HG-activated NLRP3 inflammasome. CI - Copyright (c) 2021 Zhao, Wang, Yan, Zhou, Huang, Zhu, Ye, Zhang, Chen, Chen and Zheng. FAU - Zhao, Yan AU - Zhao Y AD - Institute of Wudang Traditional Chinese Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China. AD - College of Pharmacy, Hubei University of Medicine, Shiyan, China. FAU - Wang, Qibin AU - Wang Q AD - Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, China. FAU - Yan, Shan AU - Yan S AD - Institute of Wudang Traditional Chinese Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China. AD - College of Pharmacy, Hubei University of Medicine, Shiyan, China. FAU - Zhou, Jun AU - Zhou J AD - Institute of Wudang Traditional Chinese Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China. AD - College of Pharmacy, Hubei University of Medicine, Shiyan, China. FAU - Huang, Liangyong AU - Huang L AD - Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, China. FAU - Zhu, Haitao AU - Zhu H AD - Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, China. FAU - Ye, Fang AU - Ye F AD - Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, China. FAU - Zhang, Yonghong AU - Zhang Y AD - Institute of Wudang Traditional Chinese Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China. FAU - Chen, Lin AU - Chen L AD - Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, China. FAU - Chen, Li AU - Chen L AD - Institute of Wudang Traditional Chinese Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China. AD - Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, China. FAU - Zheng, Tao AU - Zheng T AD - Institute of Wudang Traditional Chinese Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, China. AD - Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, China. LA - eng PT - Journal Article DEP - 20210426 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8110216 OTO - NOTNLM OT - Bletilla striata OT - NLRP3 inflammasome OT - diabetic foot ulcer OT - high glucose OT - polysaccharide COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/05/14 06:00 MHDA- 2021/05/14 06:01 PMCR- 2021/04/26 CRDT- 2021/05/13 06:24 PHST- 2021/01/27 00:00 [received] PHST- 2021/04/12 00:00 [accepted] PHST- 2021/05/13 06:24 [entrez] PHST- 2021/05/14 06:00 [pubmed] PHST- 2021/05/14 06:01 [medline] PHST- 2021/04/26 00:00 [pmc-release] AID - 659215 [pii] AID - 10.3389/fphar.2021.659215 [doi] PST - epublish SO - Front Pharmacol. 2021 Apr 26;12:659215. doi: 10.3389/fphar.2021.659215. eCollection 2021.