{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T16:26:05Z","timestamp":1773851165600,"version":"3.50.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Chronic skin wounds caused by diabetes, peripheral artery disease, pressure ulcers, and venous insufficiency do not fully recover anatomically and functionally. We previously found that topical application of 3% WIN-1001X cream reduces skin inflammation. In this study, we investigated whether 3% WIN-1001X cream alleviates chronic skin wounds exhibiting prolonged and extensive inflammation using streptozotocin-induced diabetic mouse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      WIN-1001X contained 20% ethanol extracts of three botanical drugs:\n                      <jats:italic>Polygala tenuifolia<\/jats:italic>\n                      Willd.,\n                      <jats:italic>Angelica tenuissima<\/jats:italic>\n                      Nakai, and\n                      <jats:italic>Dimocarpus longan<\/jats:italic>\n                      Lour. Streptozotocin-induced diabetic mice were used as a chronic wound model. After making full-thickness excision wounds were made on shaved dorsal skin, 3% WIN-1001X cream was topically applied daily for 12 days. The wound area was measured, and histology was performed to detect granulation tissue and collagen deposition. Quantitative real-time PCR and immunohistochemistry were performed to measure expression of RNA and proteins related to wound healing such as pro-inflammatory cytokines, growth factors, anti-microbial peptides, cell proliferation, keratinocyte differentiation, myofibroblast formation, and macrophage infiltration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Topical application of 3% WIN-1001X cream suppressed infiltration of neutrophils and monocytes as well as pro-inflammatory cytokine gene activation in diabetic mouse skin. It also promotes M1 to M2 macrophage polarization. Interestingly, 3% WIN-1001X cream activated the gene expression of anti-microbial peptides. Furthermore, It upregulated gene expression of\n                      <jats:italic>PDGF\u03b2, HGF, KGF<\/jats:italic>\n                      , and\n                      <jats:italic>TGF\u03b2<\/jats:italic>\n                      , resulting in the promotion of cell proliferation, granulation tissue formation, myofibroblast formation, and keratinocyte differentiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>3% WIN-1001X cream suppressed skin inflammation through decreased cytokine gene expression, immune cell infiltration, and increased macrophage polarization. It also promoted cell proliferation, granulation tissue formation, and myofibroblast transition. Furthermore, 3% WIN-1001X cream promoted keratinocyte re-epithelialization and differentiation as well as increased collagen deposition in chronic skin wounds. Thus, our results suggest that 3% WIN-1001X cream may help alleviate chronic skin wounds.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1779494","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:17:01Z","timestamp":1773829021000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Extract of Polygala tenuifolia, Angelica tenuissima, and Dimocarpus longan improve skin wound healing in streptozotocin- induced diabetic mouse"],"prefix":"10.3389","volume":"17","author":[{"given":"Hayan","family":"Jeong","sequence":"first","affiliation":[{"name":"Department of Life Science, Sogang University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyo-Jin","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Life Science, Sogang University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yejin","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Life Science, Sogang University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jungtae","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Life Science, Sogang University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeon Jae","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Life Science, Sogang University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su Young","family":"Moon","sequence":"additional","affiliation":[{"name":"R&D Center, Medi Help Line Co.","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jangho","family":"So","sequence":"additional","affiliation":[{"name":"Department of Life Science, Sogang University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In Ho","family":"Jung","sequence":"additional","affiliation":[{"name":"R&D Center, Medi Help Line Co.","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ok Nam","family":"Park","sequence":"additional","affiliation":[{"name":"R&D Center, Medi Help Line Co.","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bong-Gun","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Life Science, Sogang University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"B1","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":"B2","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.jss.2008.04.023","article-title":"The role of vascular endothelial growth factor in wound healing","volume":"153","author":"Bao","year":"2009","journal-title":"J. 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