{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:51:25Z","timestamp":1788187885073,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T00:00:00Z","timestamp":1573084800000},"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","award":["81603256"],"award-info":[{"award-number":["81603256"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"project of China Association of Chinese Medicine","award":["CACM-2018-QNRC2-B08"],"award-info":[{"award-number":["CACM-2018-QNRC2-B08"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["BUCM-2019-JCRC002, BUCM-2018-2020 and 2019-JYB-TD005"],"award-info":[{"award-number":["BUCM-2019-JCRC002, BUCM-2018-2020 and 2019-JYB-TD005"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Key Laboratory for Basic and Development Research on Chinese Medicine","award":["Beijing, 100102"],"award-info":[{"award-number":["Beijing, 100102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Diosgenin, a natural product with steroidal structure, has a wide range of clinical applications in China. It also shows great potential in the treatment of blood clots and nerve damage. To enhance the bioavailability as well as efficacy of diosgenin, eighteen diosgenin-amino acid derivatives were designed and synthesized. The neuroprotective effects of these compounds were evaluated by SH-SY5Y cell line and the biosafety was evaluated by H9c2 cell line. The results displayed that part of the derivatives\u2019 activities (EC50 &lt; 20 \u03bcM) were higher than positive control edaravone (EC50 = 21.60 \u00b1 3.04 \u03bcM), among which, DG-15 (EC50 = 6.86 \u00b1 0.69 \u03bcM) exhibited the best neuroprotection. Meanwhile, biosafety evaluation showed that DG-15 had no cytotoxicity on H9c2 cell lines. Interestingly, combined neuroprotective and cytotoxic results, part of the derivatives without their protecting group were superior to compounds with protecting group. Subsequently, Giemsa staining and DAPI (4\u2032,6-diamidino-2-phenylindole) staining indicated that DG-15 had a protective effect on damaged SH-SY5Y cells by reducing apoptosis. Moreover, DG-15 showed a higher role in promoting angiogenesis at high concentrations (4 mg\/mL) on the chorioallantoic membrane model. This finding displayed that DG-15 had dual functions of neuroprotection and angiogenesis, which provided further insight into designing agent for the application in treatment of ischemic stroke.<\/jats:p>","DOI":"10.3390\/molecules24224025","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T06:52:36Z","timestamp":1573109556000},"page":"4025","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Design, Synthesis and Biological Evaluation of Diosgenin-Amino Acid Derivatives with Dual Functions of Neuroprotection and Angiogenesis"],"prefix":"10.3390","volume":"24","author":[{"given":"Desheng","family":"Cai","sequence":"first","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinchai","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Jia","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongshan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6765-9545","authenticated-orcid":false,"given":"Penglong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6765-9545","authenticated-orcid":false,"given":"Haimin","family":"Lei","sequence":"additional","affiliation":[{"name":"School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/ana.22236","article-title":"Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate\u2013activated kinase pathway","volume":"69","author":"Wang","year":"2011","journal-title":"Ann. 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