活性导向分离瓜蒌皮中具有抗血管紧张素转化酶作用的成分(1)
[摘要]该试验基于活性导向分离瓜蒌皮中具有抗血管紧张素转化酶(ACE)作用的成分。瓜蒌皮经水提醇沉后取上清液，然后透析截留获1 000以上的部分得GLP，GLP经活性跟踪测定，DEAE Sepharose Fast Flow阴离子交换树脂分离和Superdex75系列凝胶纯化后得GLP11，并对GLP11进行HPGPC分析、单糖组成测定和ACE抑制活性检测。结果显示，采用活性跟踪方法，从瓜蒌皮中得到一种具有ACE抑制作用的均一低聚糖GLP11，相对分子质量为1 367，主要由阿拉伯糖、甘露糖和葡萄糖组成，3种单糖的摩尔比为02∶43∶100，GLP11表现出较强的ACE抑制活性，其IC50为(1134±86) mg·L-1。从瓜蒌皮中成功分离到具有ACE抑制作用的低聚糖，该发现为瓜蒌皮的化学物质基础提供依据。
[关键词]瓜蒌皮； 低聚糖； 活性导向分离； 血管紧张素转化酶(ACE)抑制作用
Bioactivityguided isolation of antiangiotensin converting
, 百拇医药
enzyme constituents from Trichosanthis Pericarpium
WANG Huijun， KE Ying， YE Guan*
(Shanghai Pharmaceuticals Holding Co.， Ltd.， Shanghai 201203， China)
[Abstract]To isolate the antiangiotensin converting enzyme (ACE) constituents from Trichosanthis Pericarpium based on bioactivityguided separation Trichosanthis Pericarpium was extracted with boiling water and precipitated by ethanol， then its supernatant was collected and dialyzed The retentate of the fractions above 1 000 was lyophilized to obtain GLP， which was then successively separated by DEAE Sepharose fast flow anionexchange and Superdex75 gel permeation chromatographic steps to achieve GLP11 A combination of HPGPC， monosaccharide compositions determination and ACE inhibitory activity studies was performed to investigate the structure and bioactivity The results showed that an antiangiotensin converting enzyme oligosaccharide， GLP11， was obtained from Trichosanthis Pericarpium based on activity tracking， whose average molecular weight was estimated to 1 367； mainly composed of arabinose， mannose， and glucose at a ratio of 02∶43∶100 GLP11 showed potent antiangiotensin converting enzyme effect with the IC50of (1134±86) mg·L-1 In this study， an oligosaccharide with antiangiotensin converting enzyme effect was isolated from Trichosanthis Pericarpium， which could lay the foundation for the substance basis study of Trichosanthis Pericarpium.
, 百拇医药
[Key words]Trichosanthis Pericarpium； oligosaccharide； activityguided isolation； anti angiotensin converting enzyme (ACE) effect
瓜蒌皮Trichosanthis Pericarpium为葫芦科栝楼属植物栝楼Trichosanthes kirilowii Maxim或双边栝楼T rosthorinii Harms的干燥成熟果皮[1]。瓜蒌皮注射液为上药集团旗下子公司上海第一生化药业有限公司独家产品，是以瓜蒌皮为原料，经水提醇沉，再经过离子交换树脂洗脱而制成的灭菌水溶液，临床上用于冠心病，稳定型心绞痛的治疗，具有行气除满，开胸除痹之功效[2]。瓜蒌皮注射液临床应用广泛，但物质基础尚不明确。目前对瓜蒌皮的化学成分研究也主要集中在小分子上，如从瓜蒌皮中分离出脂肪酸[3]、甾醇[45]、黄酮[6]、氨基酸[7]、核苷酸[8]和生物碱[910]成分，但瓜蒌皮聚糖类成分却鲜有报道。肾素血管紧张素系统(RAS)和激肽释放酶激肽系统(KKS)对机体血压、电解质和体液平衡的维持都起着重要的作用。在RASKKS系统中血管紧张素转化酶(ACE)起着至关重要的作用，ACE能催化血管紧张素I(angiotensin I，Ang I)转变为强效升高血压作用的物质血管紧张素Ⅱ(angiotensin Ⅱ，Ang Ⅱ)，与此同时，还将具有降压作用物质舒缓激肽(bradykinin)降解，使之失去降压作用，从而参与血压调节[1112]。大规模临床试验数据显示，血管紧张素转换酶抑制剂(ACEI)类药物能显著降低冠心病患者的死亡率和再发主要心血管事件的风险[13]。鉴于此，本文将瓜蒌皮按照瓜蒌皮注射液国家药品标准进行提取，并以抗ACE活性跟踪为前提，对透析截留后的袋内大分子部分进行活性跟踪分离纯化和结构分析，为阐明瓜蒌皮注射液的化學物质基础提供依据。, http://www.100md.com(王辉俊 柯樱 叶冠)
[关键词]瓜蒌皮； 低聚糖； 活性导向分离； 血管紧张素转化酶(ACE)抑制作用
Bioactivityguided isolation of antiangiotensin converting
, 百拇医药
enzyme constituents from Trichosanthis Pericarpium
WANG Huijun， KE Ying， YE Guan*
(Shanghai Pharmaceuticals Holding Co.， Ltd.， Shanghai 201203， China)
[Abstract]To isolate the antiangiotensin converting enzyme (ACE) constituents from Trichosanthis Pericarpium based on bioactivityguided separation Trichosanthis Pericarpium was extracted with boiling water and precipitated by ethanol， then its supernatant was collected and dialyzed The retentate of the fractions above 1 000 was lyophilized to obtain GLP， which was then successively separated by DEAE Sepharose fast flow anionexchange and Superdex75 gel permeation chromatographic steps to achieve GLP11 A combination of HPGPC， monosaccharide compositions determination and ACE inhibitory activity studies was performed to investigate the structure and bioactivity The results showed that an antiangiotensin converting enzyme oligosaccharide， GLP11， was obtained from Trichosanthis Pericarpium based on activity tracking， whose average molecular weight was estimated to 1 367； mainly composed of arabinose， mannose， and glucose at a ratio of 02∶43∶100 GLP11 showed potent antiangiotensin converting enzyme effect with the IC50of (1134±86) mg·L-1 In this study， an oligosaccharide with antiangiotensin converting enzyme effect was isolated from Trichosanthis Pericarpium， which could lay the foundation for the substance basis study of Trichosanthis Pericarpium.
, 百拇医药
[Key words]Trichosanthis Pericarpium； oligosaccharide； activityguided isolation； anti angiotensin converting enzyme (ACE) effect
瓜蒌皮Trichosanthis Pericarpium为葫芦科栝楼属植物栝楼Trichosanthes kirilowii Maxim或双边栝楼T rosthorinii Harms的干燥成熟果皮[1]。瓜蒌皮注射液为上药集团旗下子公司上海第一生化药业有限公司独家产品，是以瓜蒌皮为原料，经水提醇沉，再经过离子交换树脂洗脱而制成的灭菌水溶液，临床上用于冠心病，稳定型心绞痛的治疗，具有行气除满，开胸除痹之功效[2]。瓜蒌皮注射液临床应用广泛，但物质基础尚不明确。目前对瓜蒌皮的化学成分研究也主要集中在小分子上，如从瓜蒌皮中分离出脂肪酸[3]、甾醇[45]、黄酮[6]、氨基酸[7]、核苷酸[8]和生物碱[910]成分，但瓜蒌皮聚糖类成分却鲜有报道。肾素血管紧张素系统(RAS)和激肽释放酶激肽系统(KKS)对机体血压、电解质和体液平衡的维持都起着重要的作用。在RASKKS系统中血管紧张素转化酶(ACE)起着至关重要的作用，ACE能催化血管紧张素I(angiotensin I，Ang I)转变为强效升高血压作用的物质血管紧张素Ⅱ(angiotensin Ⅱ，Ang Ⅱ)，与此同时，还将具有降压作用物质舒缓激肽(bradykinin)降解，使之失去降压作用，从而参与血压调节[1112]。大规模临床试验数据显示，血管紧张素转换酶抑制剂(ACEI)类药物能显著降低冠心病患者的死亡率和再发主要心血管事件的风险[13]。鉴于此，本文将瓜蒌皮按照瓜蒌皮注射液国家药品标准进行提取，并以抗ACE活性跟踪为前提，对透析截留后的袋内大分子部分进行活性跟踪分离纯化和结构分析，为阐明瓜蒌皮注射液的化學物质基础提供依据。, http://www.100md.com(王辉俊 柯樱 叶冠)