{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:12:53Z","timestamp":1789517573750,"version":"build-2803163510"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Introduction<\/jats:title>\n Diabetic ulcers are one of the most common clinical complications of diabetes. These ulcers are characterized by poor healing and high recurrence rates, which lead to heavy medical burdens and greatly elevate the risk of limb amputation. They have therefore become a critical challenge for clinical tissue repair. Jiedu-Shengji Ointment (JDSJG) is a topical preparation composed of scorpio, scolopendra, frankincense and myrrh. Existing studies have verified its efficacy in promoting diabetic wound healing. Nevertheless, the specific molecular mechanisms responsible for its wound-healing activity remain poorly elucidated. This study aimed to preliminarily explore the molecular mechanisms by which JDSJG facilitates diabetic wound repair.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We established a mouse model of diabetic skin wounds using streptozotocin (STZ) induction combined with full-thickness skin puncture. We then detected and evaluated multiple indicators of wound tissue, including tissue microstructure and repair status, skin macrophage polarization, the mRNA and protein levels of inflammatory factors, as well as the key gene and protein expression of the NLRP3\/Caspase-1\/GSDMD signaling pathway. In the\n in vitro<\/jats:italic>\n experiment, we induced pyroptosis in RAW264.7 cells via lipopolysaccharide (LPS) stimulation. We further observed cellular morphological changes, detected cell pyroptosis and macrophage polarization, and measured the expression of inflammatory factors and key molecules in the NLRP3\/Caspase-1\/GSDMD pathway. Finally, we adopted LC-MS\/MS and GO and KEGG enrichment analyses to clarify the material basis and potential molecular mechanisms of JDSJG.\n <\/jats:p>\n <\/jats:sec>\n \n Results and discussion<\/jats:title>\n \n In a mouse model of diabetic wounds, treatment with JDSJG effectively alleviated the inflammatory response and significantly promoted the healing process of diabetic wounds in mice.\n In vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n experiments confirmed that JDSJG downregulated the expression of inflammatory cytokines and inhibited the activation of the NLRP3\/Caspase-1\/GSDMD pathway. Additionally, flow cytometry results indicated that JDSJG can induce the polarization of macrophages toward the anti-inflammatory M2 phenotype. LC-MS\/MS and network pharmacology analyses confirmed that the primary ingredients of JDSJG\u2014scorpio and scolopendra\u2014are associated with pyroptosis. Overall, this study established the therapeutic efficacy of JDSJG in promoting diabetic wound repair and highlighted its potential in regulating wound inflammation and macrophage polarization.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1865157","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T04:20:52Z","timestamp":1783311652000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Jiedu-Shengji Ointment promotes diabetic wound repair by inhibiting the NLRP3\/Caspase-1\/GSDMD signaling pathway and regulating macrophage function"],"prefix":"10.3389","volume":"17","author":[{"given":"Letian","family":"Guo","sequence":"first","affiliation":[{"name":"College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]},{"name":"Department of Burn Plastic Surgery, The First Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]},{"name":"Hunan Provincial Key Laboratory of Vascular Biology and Translational Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yarong","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Burn Plastic Surgery, The First Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]},{"name":"Hunan Provincial Key Laboratory of Vascular Biology and Translational Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangxi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Burn Plastic Surgery, The First Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Burn Plastic Surgery, The First Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Vascular Biology and Translational Medicine","place":["Changsha, Hunan, China"]},{"name":"College of Medical, Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinling","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Burn Plastic Surgery, The First Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongzhi","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]},{"name":"Department of Burn Plastic Surgery, The First Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]},{"name":"Hunan Provincial Key Laboratory of Vascular Biology and Translational Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2337\/dci22-0043","article-title":"Etiology, epidemiology, and disparities in the burden of diabetic foot ulcers","volume":"46","author":"McDermott","year":"2023","journal-title":"Diabetes Care"},{"key":"B2","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1001\/jama.2023.10578","article-title":"Diabetic foot ulcers: a review","volume":"330","author":"Armstrong","year":"2023","journal-title":"JAMA"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(24)00110-4","article-title":"Causes, prevention, and management of diabetes-related foot ulcers","volume":"12","author":"Jeffcoate","year":"2024","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.115120","article-title":"Thou shall not heal: overcoming the non-healing behaviour of diabetic foot ulcers by engineering the inflammatory microenvironment","volume":"203","author":"Monaghan","year":"2023","journal-title":"Adv Drug Delivery Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101129","article-title":"Targeting phenylpyruvate restrains excessive NLRP3 inflammasome activation and pathological inflammation in diabetic wound healing","volume":"4","author":"Lv","year":"2023","journal-title":"Cell Rep Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2268-0","article-title":"Transition from inflammation to proliferation: a critical step during wound healing","volume":"73","author":"Land\u00e9n","year":"2016","journal-title":"Cell Mol Life Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2025.102119","article-title":"AhR deficiency exacerbates inflammation in diabetic wounds via impaired mitophagy and cGAS-STING-NLRP3 activation: therapeutic potential of hydrogels loaded with FICZ","volume":"34","author":"Wang","year":"2025","journal-title":"Mater Today Bio"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.122228","article-title":"Molecular pathways of NF-\u0138B and NLRP3 inflammasome as potential targets in the treatment of inflammation in diabetic wounds: a review","volume":"334","author":"Teh","year":"2023","journal-title":"Life Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202505179","article-title":"Spatiotemporal immunomodulation of macrophages via NLRP3\/IL-1\u03b2 pathway by core-shell microneedles to promote healing of biofilm-infected diabetic ulcers","volume":"21","author":"Yang","year":"2025","journal-title":"Small"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9687925","article-title":"Relevance of NLRP3 inflammasome-related pathways in the pathology of diabetic wound healing and possible therapeutic targets","volume":"2022","author":"Ding","year":"2022","journal-title":"Oxid Med Cell Longev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2021.0148","article-title":"Targeting the NOD-like receptor pyrin domain containing 3 inflammasome to improve healing of diabetic wounds","volume":"12","author":"Cavalcante-Silva","year":"2023","journal-title":"Adv Wound Care (New Rochelle)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.13359\/j.cnki.gzxbtcm.2025.06.037","article-title":"Visualized analysis of research on traditional Chinese medicine in treating chronic refractory wounds in the recent 10 years","volume":"42","author":"Feng","year":"2025","journal-title":"J Guangzhou Univ Tradit Chin Med"},{"key":"B13","article-title":"Effectiveness analysis of Jiedu Shengji ointment in treating refractory diabetic wound","volume":"18","author":"Yang","year":"2022","journal-title":"Asia-Pacific Tradit Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.13406\/j.cnki.cyxb.003338","article-title":"Effect of Jiedu Shengji ointment on alleviating inflammation and promoting chronic wound repair in diabetic SD rats via regulating GSK-3\u03b2\/\u03b2-catenin","volume":"48","author":"Yuan","year":"2023","journal-title":"J Chongqing Med Univ"},{"key":"B15","doi-asserted-by":"publisher","first-page":"709","DOI":"10.19945\/j.cnki.issn.1006-3250.2022.05.033","article-title":"A method for establishing a mouse model of type 2 diabetic yin syndrome wound with high modeling rate and high stability","volume":"28","author":"Huang","year":"2022","journal-title":"Chin J Basic Med Tradit Chin Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26146909","article-title":"From control to cure: insights into the synergy of glycemic and antibiotic management in modulating the severity and outcomes of diabetic foot ulcers","volume":"26","author":"Omotosho","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.7150\/thno.117949","article-title":"Recent advances and challenges in hydrogel-based delivery of immunomodulatory strategies for diabetic wound healing","volume":"16","author":"Du","year":"2026","journal-title":"Theranostics"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1591944","article-title":"Single-cell atlas of human skin implicates APOE pro-inflammatory signaling in diabetic foot ulcers","volume":"16","author":"Yin","year":"2025","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1625474","article-title":"Mitochondrial dysfunction in diabetic ulcers: pathophysiological mechanisms and targeted therapeutic strategies","volume":"13","author":"Pan","year":"2025","journal-title":"Front Cell Dev Biol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1368835","article-title":"NLRP3 inflammasome and pyroptosis in cardiovascular diseases and exercise intervention","volume":"15","author":"Ding","year":"2024","journal-title":"Front Pharmacol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1624770","article-title":"NLRP3 and beyond: inflammasomes as central cellular hub and emerging therapeutic target in inflammation and disease","volume":"16","author":"Pinz\u00f3n-Fern\u00e1ndez","year":"2025","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics17101295","article-title":"Application of biomaterials in diabetic wound healing: the recent advances and pathological aspects","volume":"17","author":"Han","year":"2025","journal-title":"Pharmaceutics"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70378","article-title":"Immunomodulatory mechanisms of chronic wound healing: translational and clinical relevance","volume":"6","author":"Riaz","year":"2025","journal-title":"MedComm"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3724\/zdxbyxb-2025-0464","article-title":"Single-cell transcriptomic analysis reveals immune dysregulation and macrophage reprogramming in diabetic foot ulcers","volume":"54","author":"Huang","year":"2025","journal-title":"Zhejiang Da Xue Xue Bao Yi Xue Ban"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2021.06.013","article-title":"Macrophage-mediated inflammation in diabetic wound repair","volume":"119","author":"Wolf","year":"2021","journal-title":"Semin Cell Dev Biol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"392","DOI":"10.18632\/aging.204053","article-title":"Scorpion and centipede alleviates severe asthma through M2 macrophage-derived exosomal miR-30b-5p","volume":"14","author":"Tang","year":"2022","journal-title":"Aging (Albany NY)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.16333\/j.1001-6880.2025.3.014","article-title":"Study on the mechanism of frankincense volatile oil in improving cardiac hypertrophy in rats by inhibiting NLRP3 inflammasome","volume":"37","author":"Qiu","year":"2025","journal-title":"Nat Prod Res Dev"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1692443","article-title":"From bench to bedside, boswellic acids in anti-inflammatory therapy - mechanistic insights, bioavailability challenges, and optimization approaches","volume":"16","author":"Peng","year":"2025","journal-title":"Front Pharmacol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s11481-025-10251-0","article-title":"Gallic acid alleviates cerebral ischemia-reperfusion injury in mice by mediating microglial polarization through the NLRP3\/mTOR axis","volume":"20","author":"Hua","year":"2025","journal-title":"J Neuroimmune Pharmacol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29184315","article-title":"An unprecedented 4,8-cycloeudesmane, further new sesquiterpenoids, a triterpene, steroids, and a lignan from the resin of Commiphora myrrha and their anti-inflammatory activity in vitro","volume":"29","author":"Unterholzner","year":"2024","journal-title":"Molecules"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S82272","article-title":"Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic \u03b2 cell glucotoxicity","volume":"8","author":"Wu","year":"2015","journal-title":"Diabetes Metab Syndr Obes"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5281358","article-title":"NLRP3 inflammasome expression and signaling in human diabetic wounds and in high glucose induced macrophages","volume":"2017","author":"Zhang","year":"2017","journal-title":"J Diabetes Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12051079","article-title":"Antioxidant activities of natural compounds from Caribbean plants to enhance diabetic wound healing","volume":"12","author":"Accipe","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1549749","article-title":"LPS-induced extracellular AREG triggers macrophage pyroptosis through the EGFR\/TLR4 signaling pathway","volume":"16","author":"Yuan","year":"2025","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/s41573-021-00154-z","article-title":"Channelling inflammation: gasdermins in physiology and disease","volume":"20","author":"Liu","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104481","article-title":"Pyroptosis: a form of cell death depending on plasma membrane nanopores formation","volume":"25","author":"Li","year":"2022","journal-title":"iScience"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.37349\/emed.2025.1001326","article-title":"The significance of inflammasome activation during each phase of wound healing","volume":"6","author":"Artlett","year":"2025","journal-title":"Explor Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0326-4","article-title":"Cell death in the gut epithelium and implications for chronic inflammation","volume":"17","author":"Patankar","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1186\/s13075-025-03679-5","article-title":"Bone marrow mesenchymal stem cell-derived exosomes improve pyroptosis and mitochondrial integrity through miR-515-5p-mediated TLR4\/NLRP3\/GSDMD axis in rheumatoid arthritis","volume":"27","author":"Cai","year":"2025","journal-title":"Arthritis Res Ther"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.14397","article-title":"Interleukin-37 promotes wound healing in diabetic mice by inhibiting the MAPK\/NLRP3 pathway","volume":"16","author":"Cui","year":"2025","journal-title":"J Diabetes Investig"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jrras.2025.101614","article-title":"Macrophage pyroptosis promotes cardiac fibroblast activation and myocardial fibrosis via the Hedgehog signaling pathway in radiation-induced heart damage","volume":"18","author":"Yuan","year":"2025","journal-title":"J Radiat Res Appl Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.24272\/j.issn.2095-8137.2025.509","article-title":"Peptides derived from exocrine secretions of venomous animals used as traditional Chinese \"worm\" medicines","volume":"47","author":"Lai","year":"2026","journal-title":"Zool Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3390\/ph18101438","article-title":"Peptides from animal venoms: a promising frontier in diabetes therapy via multi-target mechanisms","volume":"18","author":"de Almeida","year":"2025","journal-title":"Pharmaceuticals"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.119872","article-title":"Animal-derived peptides from traditional Chinese medicines: medicinal potential, mechanisms, and prospects","volume":"349","author":"Zhang","year":"2025","journal-title":"J Ethnopharmacol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117476","article-title":"Mechanisms and therapeutic strategies for NLRP3 degradation via post-translational modifications in ubiquitin-proteasome and autophagy lysosomal pathway","volume":"289","author":"Su","year":"2025","journal-title":"Eur J Med Chem"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2025.104891","article-title":"A review of the relationship between inflammasomes and autophagy in cancers: recent advances and future directions","volume":"215","author":"Zhang","year":"2025","journal-title":"Crit Rev Oncol Hematol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1761361","article-title":"Taking its TOLL: the role of toll-like receptor 4 in human health and disease, and its potential as a therapeutic target","volume":"17","author":"Crammond","year":"2026","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.8486","article-title":"Loureirin B accelerates diabetic wound healing by promoting TGF\u03b2\/Smad-dependent macrophage M2 polarization: a concerted analytical approach through single-cell RNA sequencing and experimental verification","volume":"39","author":"Fan","year":"2025","journal-title":"Phytother Res"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1007\/s11033-025-11116-8","article-title":"The NLRP3 inflammasome: a pivotal orchestrator of multisystem diseases-from molecular mechanisms to therapeutic innovation","volume":"52","author":"Xiao","year":"2025","journal-title":"Mol Biol Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1865157\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T04:20:57Z","timestamp":1783311657000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1865157\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,6]]},"references-count":49,"alternative-id":["10.3389\/fimmu.2026.1865157"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1865157","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,6]]},"article-number":"1865157"}}