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水仙苷 A 从冲绳蜂胶中分离出来，通过失活存活信号抑制血管生成并诱导半胱天冬酶依赖性细胞凋亡。

Nymphaeol-A Isolated from Okinawan Propolis Suppresses Angiogenesis and Induces Caspase-Dependent Apoptosis via Inactivation of Survival Signals.

机构信息

Department of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.

出版信息

Evid Based Complement Alternat Med. 2013;2013:826245. doi: 10.1155/2013/826245. Epub 2013 Apr 24.

DOI:10.1155/2013/826245
PMID:23710238
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3655572/
Abstract

Propolis, a resinous substance that honeybees collect to protect their beehive from enemies, is reported to have various biological activities. In our screening program to search for antiangiogenic compounds from propolis, the ethanol extracts of Okinawan propolis (EEOP) showed significant antiangiogenic activities in a tube formation assay with human umbilical vein endothelial cells (HUVECs) in vitro at 3.13  μ g/mL and chorioallantoic membrane (CAM) assay in vivo at 25  μ g/egg. To elucidate the active compounds of EEOP and their mode of action, we isolated some prenylated flavonoids from EEOP and found that nymphaeol-A had the strongest antiangiogenic activity among them. Nymphaeol-A significantly reduced in vivo neovessel formation in the CAM assay at 25  μ g/egg. At the molecular level, nymphaeol-A markedly inactivated mitogen-activated protein kinase/ERK kinase 1/2 (MEK1/2) and extracellular signal-regulated kinase 1/2 (ERK1/2), whose molecular activations signal new vessel formation in HUVECs. In addition, nymphaeol-A dose- and time-dependently induced caspase-dependent apoptosis in tube-forming HUVECs. Taken together, nymphaeol-A was shown to inhibit angiogenesis at least in part via inactivation of MEK1/2-ERK1/2 signaling and induction of caspase-dependent apoptosis. Okinawan propolis and its major component, nymphaeol-A, may be useful agents for preventing tumor-induced angiogenesis.

摘要

蜂胶是蜜蜂为了保护蜂巢免受敌人侵害而采集的一种树脂状物质，据报道具有多种生物活性。在我们从蜂胶中寻找抗血管生成化合物的筛选计划中，冲绳蜂胶的乙醇提取物（EEOP）在 3.13μ g/mL 的体外人脐静脉内皮细胞（HUVEC）管形成测定和 25μ g/卵的体内鸡胚尿囊膜（CAM）测定中表现出显著的抗血管生成活性。为了阐明 EEOP 的活性化合物及其作用方式，我们从 EEOP 中分离出一些类异戊二烯黄酮，并发现荷叶醇-A 是其中具有最强抗血管生成活性的化合物。荷叶醇-A 可显著减少 CAM 测定中体内新血管形成，在 25μ g/卵时效果最佳。在分子水平上，荷叶醇-A 明显失活丝裂原活化蛋白激酶/细胞外信号调节激酶激酶 1/2（MEK1/2）和细胞外信号调节激酶 1/2（ERK1/2），其分子激活信号在 HUVEC 中形成新血管。此外，荷叶醇-A 可剂量和时间依赖性诱导形成管状的 HUVEC 中的半胱天冬酶依赖性细胞凋亡。综上所述，荷叶醇-A 至少部分通过失活 MEK1/2-ERK1/2 信号和诱导半胱天冬酶依赖性细胞凋亡来抑制血管生成。冲绳蜂胶及其主要成分荷叶醇-A 可能是预防肿瘤诱导血管生成的有用药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b53/3655572/d5dda1f92eba/ECAM2013-826245.010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b53/3655572/f1105f874ef9/ECAM2013-826245.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b53/3655572/908e5fb48e94/ECAM2013-826245.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b53/3655572/8f1e7f95652f/ECAM2013-826245.003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b53/3655572/7c7fbdb4517d/ECAM2013-826245.006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b53/3655572/4b04581a0b64/ECAM2013-826245.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b53/3655572/7e676f3b264d/ECAM2013-826245.009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b53/3655572/f1105f874ef9/ECAM2013-826245.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b53/3655572/908e5fb48e94/ECAM2013-826245.002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b53/3655572/f51a6c19d3f4/ECAM2013-826245.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b53/3655572/7c7fbdb4517d/ECAM2013-826245.006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b53/3655572/d5dda1f92eba/ECAM2013-826245.010.jpg

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