{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:03:55Z","timestamp":1789625035281,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"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":"\n Background<\/jats:title>\n Diabetic wounds are characterized by delayed repair associated with persistent inflammation, oxidative stress, fibroblast dysfunction, mitochondrial injury, and impaired angiogenesis. Scutellarein (SCU), a structurally defined plant-derived flavonoid metabolite, has documented antioxidant and anti-inflammatory activities; however, its role and the mechanistically relevant pathways engaged in diabetic wound repair, particularly those involving calcium-mitochondrial homeostasis and purinergic signaling, remain incompletely defined.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We administered local SCU in a streptozotocin-induced diabetic mouse cutaneous wound model and, in\n \n \n \n \n \n H<\/mml:mtext>\n <\/mml:mrow>\n \n 2<\/mml:mn>\n <\/mml:mrow>\n <\/mml:msub>\n \n \n O<\/mml:mtext>\n <\/mml:mrow>\n \n 2<\/mml:mn>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n -injured L929 fibroblasts, assessed scratch closure, survival, redox balance, mitochondrial morphology and function, and calcium overload. We then used RNA sequencing (RNA-seq) and adenosine triphosphate (ATP) challenge\/reversal experiments to examine purinergic calcium signaling. These analyses identified\n P2rx1<\/jats:italic>\n \u2014the gene encoding P2RX1 (P2X purinoceptor 1), an ATP-gated cation channel that mediates rapid calcium entry\u2014as a candidate purinergic signal rather than a validated target.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n SCU accelerated wound closure and increased re-epithelialization, Masson-positive collagen deposition, proliferative\n \n \n \n \u03b1<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n -SMA-positive wound cells, and angiogenic indices in diabetic wounds. In injured fibroblasts, SCU increased scratch closure, reduced cell death and reactive oxygen species (ROS) accumulation, restored the superoxide dismutase (SOD)\/malondialdehyde (MDA) balance, preserved mitochondrial morphology and membrane potential, and increased cellular ATP content. RNA-seq showed\n P2rx1<\/jats:italic>\n downregulation after SCU treatment and enrichment of calcium transport, mitochondrial, inflammatory, and wound-healing pathways. ATP addition attenuated the SCU-associated reductions in calcium overload, mitochondrial depolarization, and inflammatory gene expression, consistent with a contribution from broad purinergic calcium signaling.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n In experimental models, SCU promoted diabetic wound repair and protected fibroblasts from oxidative injury. The data support preservation of calcium-mitochondrial homeostasis as a mechanistically relevant axis, and broad purinergic signaling, possibly involving P2RX1, may contribute to these effects; direct receptor-perturbation studies are warranted.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2026.1925629","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:33:53Z","timestamp":1789623233000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Scutellarein promotes diabetic wound repair and preserves fibroblast calcium-mitochondrial homeostasis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yizhuo","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengzhou","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengling","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucheng","family":"Yao","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Department of Plastic and Reconstructive Surgery, The First People\u2019s Hospital of Lancang Lahu Autonomous County","place":["Lancang, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s11658-025-00856-x","article-title":"Targeting the sirtuin 6-nf-\u03bab p65 axis by 6-hydroxyhyoscyamine hydrobromide: a deacetylation-driven new therapy for diabetic wounds","volume":"31","author":"Chen","year":"2026","journal-title":"Cell. and Mol. 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