{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:15:40Z","timestamp":1788419740000,"version":"build-2803163510"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic foot ulcers (DFUs) represent a significant clinical challenge due to their high morbidity, infection risk, and poor healing rates. Emerging evidence highlights the therapeutic potential of Traditional Chinese Medicine in wound management. This study investigates the efficacy of Shengji Ointment (SJ)\u2014a multi-herb formulation\u2014in human subjects with DFUs and a diabetic rat model, specifically elucidating its modulation of the wound inflammatory microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The lyophilized powder of the SJ extract was analyzed using UPLC-MS\/MS to profile its chemical constituents. A single-center, prospective, randomized, controlled clinical study was conducted in patients with Wagner Grade 3 DFUs. A diabetic wound rat model was established, and proinflammatory cytokine and growth factor levels in granulation tissue were quantified at multiple time points.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>UPLC-MS\/MS identified 3,552 distinct UPLC-MS\/MS identified 3,552 distinct compounds in the SJ extract, predominantly flavonoids and alkaloids in the SJ extract, predominantly flavonoids and alkaloids; 10 high-abundance compounds were selected (5\u00a0at MSI Level 1). The clinical study demonstrated that SJ significantly accelerated DFU wound healing. The animal study revealed that SJ promotes wound healing by modulating the wound microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrated that Shengji Ointment (SJ) could inhibit excessive inflammation, promote angiogenesis and vascular maturation, and thereby markedly accelerate diabetic wound healing in both clinical settings and rat models. Such therapeutic effects may be associated with the DLL4\/Notch1-VEGF\/VEGFR2 signaling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1855791","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:40:20Z","timestamp":1788417620000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Shengji ointment accelerates diabetic foot ulcer wound healing by regulating inflammatory microenvironment"],"prefix":"10.3389","volume":"17","author":[{"given":"Rui","family":"Dai","sequence":"first","affiliation":[{"name":"Graduate School, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"Institute of TCM Ulcers, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of TCM Ulcers, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"Department of Traditional Chinese Surgery, Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinpeng","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Peripheral Vascular Diseases, Shandong University of Traditional Chinese Medicine Affiliated Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YunSha","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of TCM Ulcers, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HongBin","family":"Liu","sequence":"additional","affiliation":[{"name":"Heping District Health Commission","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of TCM Ulcers, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"Department of Traditional Chinese Surgery, Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaojun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of TCM Ulcers, Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]},{"name":"Department of Traditional Chinese Surgery, Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e100607","DOI":"10.7759\/cureus.100607","article-title":"Histological and immunohistochemical biomarkers for wound age estimation in human skin: a systematic review","volume":"18","author":"Ahmed","year":"2026","journal-title":"Cureus"},{"key":"B2","doi-asserted-by":"publisher","first-page":"4917","DOI":"10.3390\/molecules26164917","article-title":"Skin wound healing: normal macrophage function and macrophage dysfunction in diabetic wounds","volume":"26","author":"Aitcheson","year":"2021","journal-title":"Molecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"131743","DOI":"10.1016\/j.foodchem.2021.131743","article-title":"Extraction, isolation and identification of four phenolic compounds from Pleioblastus amarus shoots and their antioxidant and anti-inflammatory properties in vitro","volume":"374","author":"Ao","year":"2022","journal-title":"Food Chem."},{"key":"B4","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":"B5","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1007\/s12325-014-0140-x","article-title":"Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights","volume":"31","author":"Baltzis","year":"2014","journal-title":"Adv. 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