{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:48:02Z","timestamp":1782362882435,"version":"3.54.5"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"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>\n                      <jats:italic>Salvia miltiorrhiza-Dalbergia odorifera<\/jats:italic>\n                      (SM-DO) is a commonly used herb pair for treating cardiovascular diseases. It can treat myocardial infarction (MI) by regulating glycolysis and angiogenesis, but the optimal proportion of its active components remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials<\/jats:title>\n                    <jats:p>Based on the enhanced simplex-centroid mixture design using Minitab 19 software, 19 proportions of salvianolic acid B (Sal-B), butein (But), tanshinone IIA (Tan IIA), and formononetin (For) were applied to an oxygen-glucose deprivation (OGD)-treated human cardiac microvascular endothelial cells (HCMVECs)-AC16 cells co-culture system. The proportions were independent variables, and viability, lactic acid, vascular endothelial growth factor (VEGF) of HCMVECs, and cardiac troponin I (cTnI) of AC16 cells were dependent variables. Regression equations were fitted and multi-objective optimization was performed to determine the OP, and experimental verification was conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Stepwise regression analysis yielded regression equations for the four response indicators. The\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      and adjusted\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      of each model were at reasonable levels, and the predicted\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      showed no significant decay. Multi-objective simultaneous optimization revealed OP of 60% Sal-B, 5% But, 5% Tan IIA, and 30% For. Experimental validation results showed that OP could promote lactic acid and VEGF production in OGD HCMVECs, enhance HCMVEC viability, and inhibit cTnI release in OGD AC16 cells.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , OP increased levels of lactic acid, total protein lactylation (Pan-Kla), and VEGF in the myocardium of MI mice, and decreased levels of cTnI, creatine kinase-myocardial band (CK-MB), and myoglobin (Myo) in serum, alleviated pathological injury and fibrosis in myocardial tissues, and enhanced cardiac function in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study preliminarily clarifies the OP composed of Sal-B, But, Tan IIA, and For that improves glycolysis and angiogenesis-related indicators and exerts cardioprotective effects, providing a new strategy for studies on active component formulations of traditional Chinese medicines. It is expected to lay a methodological foundation for the clinical application of SM-DO and the development of new drugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1783969","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:22:16Z","timestamp":1782361336000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mixture design optimization of salvianolic acid B, tanshinone IIA, butein, and formononetin from Salvia miltiorrhiza and Dalbergia odorifera for myocardial infarction"],"prefix":"10.3389","volume":"17","author":[{"given":"Weihong","family":"Li","sequence":"first","affiliation":[{"name":"College of Life Sciences, Northwest University","place":["Xi\u2019an, China"]},{"name":"College of Pharmacy, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]},{"name":"TANK Medicinal Biology Institute of Xi\u2019an","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kedi","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northwest University","place":["Xi\u2019an, China"]},{"name":"TANK Medicinal Biology Institute of Xi\u2019an","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengzhao","family":"Liu","sequence":"additional","affiliation":[{"name":"TANK Medicinal Biology Institute of Xi\u2019an","place":["Xi\u2019an, China"]},{"name":"State Key Laboratory of Flexible Electronics (LOFE) & Institute of Flexible Electronics (IFE), Northwestern Polytechnical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Dai","sequence":"additional","affiliation":[{"name":"TANK Medicinal Biology Institute of Xi\u2019an","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yao","sequence":"additional","affiliation":[{"name":"TANK Medicinal Biology Institute of Xi\u2019an","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hefei","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]},{"name":"TANK Medicinal Biology Institute of Xi\u2019an","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziheng","family":"Ding","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]},{"name":"TANK Medicinal Biology Institute of Xi\u2019an","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]},{"name":"TANK Medicinal Biology Institute of Xi\u2019an","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peifeng","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]},{"name":"National Drug Clinical Trial Institute, The Second Affiliated Hospital, Shaanxi University of Chinese Medicine","place":["Xixian New Area, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Xi","sequence":"additional","affiliation":[{"name":"TANK Medicinal Biology Institute of Xi\u2019an","place":["Xi\u2019an, China"]},{"name":"National Drug Clinical Trial Institute, The Second Affiliated Hospital, Shaanxi University of Chinese Medicine","place":["Xixian New Area, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northwest University","place":["Xi\u2019an, China"]},{"name":"School of Pharmacy, Air Force Medical University","place":["Xi\u2018an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1093\/eurheartj\/ehn281","article-title":"No-reflow: the next challenge in treatment of ST-elevation acute myocardial infarction","volume":"29","author":"Abbate","year":"2008","journal-title":"Eur. 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