{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:00:27Z","timestamp":1755597627791,"version":"3.40.5"},"reference-count":78,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Traditional Chinese Medicine Academic School Inheritance Studio Project of the State Administration of Traditional Chinese Medicine","award":["62","202004j07020046"],"award-info":[{"award-number":["62","202004j07020046"]}]},{"name":"Key R&D Program of Anhui Province, Special Project on Population Health","award":["62","202004j07020046"],"award-info":[{"award-number":["62","202004j07020046"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2022,4,11]]},"abstract":"<jats:p>Background. Naoluo Xintong decoction (NLXTD) is a traditional Chinese medicine (TCM) formula which has been used to improve neuronal functional recovery after cerebral ischemic stroke. However, the molecular mechanism underlying NLXTD\u2019s amelioration of ischemic stroke remains unclear. The present study was designed to explore the effect and mechanism of NLXTD on brain angiogenesis in a rat model with cerebral ischemia-reperfusion (I\/R) injury targeting the hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1)\/vascular endothelial growth factor (VEGF) pathway. Materials and Methods. Cerebral I\/R model was established by the classical middle cerebral artery occlusion (MCAO) method. Sprague-Dawley (SD) male rats (n\u2009=\u200980) were randomly divided into the sham-operation group, the model group, the HIF-1\u03b1 inhibitor 2-methoxyestradiol (2ME2) group, the 2ME2 with NLXTD group, and the NLXTD group. Neurological deficit test, TTC staining, H&amp;E staining, TUNEL staining, immunohistochemistry (IH), immunofluorescence (IF), western blot, and quantitative RT-PCR were performed to evaluate the effect of NLXTD after MCAO. Results. Administration of NLXTD significantly decreased neuron deficiency scores, reduced brain infarct volume, and lowered damaged and apoptotic cells after brain I\/R injury in rats. Meanwhile, NLXTD had a protective effect on angiogenesis by increasing the MVD and the expressions of BrdU and CD34, which enhanced the number of endothelial cells in the ischemic penumbra brain. NLXTD treatment significantly raised the protein and mRNA levels of HIF-1\u03b1, VEGF, VEGFR2, and Notch1 compared with the model treatment. In contrast, a specific HIF-1\u03b1 inhibitor, 2ME2, inhibited the improvement of neurological function and angiogenesis in NLXTD-induced rats with cerebral I\/R injury, suggesting that NLXTD played a positive role in ischemic brain injury by activating the HIF-1\u03b1\/VEGF signaling pathway. Conclusions. NLXTD exerts neuroprotection targeting angiogenesis by upregulating the HIF-1\u03b1\/VEGF signaling pathway on cerebral I\/R injury rats.<\/jats:p>","DOI":"10.1155\/2022\/9341466","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T17:22:50Z","timestamp":1649697770000},"page":"1-15","source":"Crossref","is-referenced-by-count":2,"title":["Naoluo Xintong Decoction Ameliorates Cerebral Ischemia-Reperfusion Injury by Promoting Angiogenesis through Activating the HIF-1\u03b1\/VEGF Signaling Pathway in Rats"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5249-7088","authenticated-orcid":true,"given":"Pei-Pei","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Xin\u2019an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui 230038, China"},{"name":"School of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui 230012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xin\u2019an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui 230038, China"},{"name":"School of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui 230012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Miao","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui 230012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue-Mei","family":"Qin","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui 230012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9151-313X","authenticated-orcid":true,"given":"Jian-Peng","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xin\u2019an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui 230038, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-014-0118-2"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-072x-5-10"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-011-0049-x"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.2147\/VHRM.S39213"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.1948-13.2014"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2019.7377"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.5374"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.3171\/2017.1.focus16515"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.s210035"},{"key":"10","first-page":"25","article-title":"Angiogenesis-possibilities, problems and perspectives","volume":"61","author":"A. 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