{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:22:15Z","timestamp":1776680535467,"version":"3.51.2"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"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>Background<\/jats:title>\n                    <jats:p>Collateral perfusion and neurovascular stability critically influence outcomes after ischemic stroke; however, no pharmacological agent is currently approved to enhance these processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Chunghyul-dan (CHD), a standardized multi-botanical ethanol extract with reported vascular and anti-inflammatory properties, was evaluated for its neurovascular protective effects in a permanent middle cerebral artery occlusion (pMCAO) mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>The Process and Methods<\/jats:title>\n                    <jats:p>\n                      Male ICR mice subjected to pMCAO received oral Chunghyul-dan (30\u2013120\u00a0mg\/kg). Cortical infarct volume, anterior cerebral artery perfusion, angiogenesis-related signaling, neuroinflammation, and endothelial barrier integrity were assessed using histological analysis, laser Doppler flowmetry, immunohistochemistry, and complementary\n                      <jats:italic>in vitro<\/jats:italic>\n                      studies in BV2 microglia and bEND.3 endothelial cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CHD significantly reduced cortical infarct volume, with maximal protection observed at 60\u00a0mg\/kg. Laser Doppler analysis demonstrated enhanced ACA perfusion at 30\u00a0mg\/kg during early ischemia. CHD upregulated VEGF expression in ischemic cortex and endothelial cells, supporting vascular remodeling. Neuroinflammation was attenuated, as CHD reduced Iba-1\u2013positive microglial activation and suppressed iNOS, IL-6, and TNF-\u03b1 expression. Endothelial barrier integrity was preserved through reduced PECAM-1 expression, restoration of claudin-5 and occludin, and selective inhibition of STAT3 phosphorylation, whereas TLR4\/MAPK signaling remained unchanged.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CHD confers multi-level neurovascular protection by promoting collateral perfusion, facilitating VEGF-associated vascular adaptation, suppressing neuroinflammation, and stabilizing endothelial junctional architecture. These findings support further translational evaluation of CHD as a pharmacological modulator of collateral circulation in ischemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1736412","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:35:02Z","timestamp":1776677702000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Chunghyul-dan, a multi-botanical ethanol extract, improves collateral perfusion and neurovascular stability in permanent focal cerebral ischemia"],"prefix":"10.3389","volume":"17","author":[{"given":"Han-Gyul","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae Woo","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University","place":["Seoul, Republic of Korea"]},{"name":"Department of Science in Korean Medicine, Graduate School, Kyung Hee University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minho","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won Myoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Dae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Plant Science and Technology, Chung-Ang University","place":["Anseong, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seungwon","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanghyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Plant Science and Technology, Chung-Ang University","place":["Anseong, Republic of Korea"]},{"name":"Natural Product Institute of Science and Technology, Chung-Ang University","place":["Anseong, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ik-Hyun","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University","place":["Seoul, Republic of Korea"]},{"name":"Department of Science in Korean Medicine, Graduate School, Kyung Hee University","place":["Seoul, Republic of Korea"]},{"name":"Institute of Convergence Korean Medicine, College of Korean Medicine, Kyung Hee University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Kwan","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1161\/STROKEAHA.122.036946","article-title":"Neuroinflammation, stroke, blood-brain barrier dysfunction, and imaging modalities","volume":"53","author":"Candelario-Jalil","year":"2022","journal-title":"Stroke"},{"key":"B2","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/nature10144","article-title":"Molecular mechanisms and clinical applications of angiogenesis","volume":"473","author":"Carmeliet","year":"2011","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"716825","DOI":"10.3389\/fncel.2021.716825","article-title":"Cerebral Edema formation after stroke: emphasis on blood-brain barrier and the lymphatic drainage system of the brain","volume":"15","author":"Chen","year":"2021","journal-title":"Front. 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