青兰属植物香青兰化学成分及活性研究
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摘要
对传统药用植物的化学成分进行系统的研究,是发现具有生物活性化合物的重要途径之一。唇形科(Labiatae)青兰属(Dracocephalum)植物约60种,主要分布在亚洲温带,多在高山及半干旱地区,少数延至中欧及北欧,1种分布在北美。我国约有32种7变种,分布于东北、华北、西北及西南地区。青兰属植物在民间被广泛应用,尤其是新疆维吾尔自治区,该属多种植物被用作气管炎和心血管疾病的治疗药物。我们选择了对心肌缺血具有保护作用的青兰属植物香青兰进行了系统的化学成分研究,对分离得到的黄酮类化合物进行活性筛选试验,并采用HPLC法测定了不同时期采收的香青兰中田蓟苷和藿香苷的含量。
香青兰(Dracocephalum moldavica L.)为一年生草本,维吾尔族和蒙古族习用药材,分布于黑龙江、吉林、辽宁、内蒙古、甘肃、山西、青海及新疆等省区,新疆南部有栽培,用于补脑安神,镇咳止喘,强心利尿。通过MCI柱色谱,硅胶柱色谱,Sephadex LH-20柱色谱从其地上全草乙醇提取物中分离得到7个三萜类成分,波谱学方法鉴定为：熊果酸(1),齐墩果酸(2),乌发醇(3),白桦酯醇(4),白桦酯酸(5),白桦酯醇-28-乙酯(6),3p,24-dihydroxyurs-12-en-28-oic acid(7)；26个黄酮类成分,鉴定为：洋芹素(8),洋芹素-7-O-β-D.葡萄吡喃糖苷(9),洋芹素-7-O-β-D-半乳吡喃糖苷(10),木犀草素(11),木犀草素-7-O-β-D-葡萄吡哺糖苷(12),金合欢素(13),acacetin-6"-glucuronide (14),栀子素乙(15),玄参黄酮(16),鼠尾草素(17),异鼠李素(18),田蓟苷(19),藿香苷(20),acacetin-7-O-glucoside-(6"-O-malonyl ester) (21), takakin-8-O-β-D-glucopyranoside (22),山柰酚(23),山柰酚-3-O-β-D-(6″-O-对羟基桂皮酰)-半乳吡喃糖苷(24),山柰酚-3-O-β-D-(6″-O-对羟基反式香豆酰基)-葡萄吡喃糖苷(25),2″-对羟基肉桂酰氧基黄芪苷(26)；苯丙素类化合物2个：迷迭香酸甲酯(27),迷迭香酸乙酯(28)；甾体类化合物3个：豆甾醇(29),p.谷甾醇(30),胡萝卜苷(31)。其中化合物10,27,28为首次从该属植物中分离得到,4,5,6,9为首次从该植物中分离得到。
Nrf2作为一种转录因子,调控了Ⅱ相酶和细胞解毒酶的表达,从而保护细胞免受自由基和外界毒物侵袭。研究表明,诱导Nrf2表达对于多种慢性疾病如心血管疾病、糖尿病的治疗均有帮助。我们对分离得到的部分化合物采用能表达荧光素的稳定细胞株进行了Nrf2诱导活性筛选,结构表明黄酮类化合物均有程度不同的诱导荧光素酶表达的作用,是潜在的Nrf2诱导剂。这种作用可能与香青兰保护心脑的功效有关。
我们选择了香青兰药材中两种黄酮苷类成分田蓟苷和藿香苷,建立了HPLC法同时测定药材中两种黄酮苷含量的方法,并且对不同采收季节的药材中两种黄酮苷的含量进行了考察,结果表明花期的香青兰田蓟苷及藿香苷含量较高,对进一步确定香青兰最佳采收期具有一定的参考意义。
Systematical study on the chemical constituents of traditional Chinese herbs is one of important routes to discover bioactive compounds. There are about 60 species belong to the genus Dracocephalum, family Labiatae. These plants distribute in alpine and semidry regions mainly in temperate Asia, with a few in Europe, one in North America. There are about 32 species,7 variations in China. Several species belong to the genus Dracocephalum are used as folk medicine for the treatment of tracheitis and cardiovascular disease in Xinjiang antonomous region. Dracocephalum moldavica can be applied for the protection of cardiac ischemia. This dissertation mainly focused on the chemical dtudies of the herbal plant. Bioactivities were investigated for some flavonoids. Determinations of tiliroside and agastachoside in D. moldavica were achieved by HPLC.
Dracocephalum moldavica L, habitually used herb by Weiwuer and Meng nationality, mainly distributed in Heilongjiang, Jilin, Liaoning, Neimenggu, Gansu, Shanxi, Qinghai and Xinjiang in China. It was an annual herb and was cultivated in southern Xinjiang autonomous region. The aerial parts of this herb were employed in smoothing the nerves, relieveing a cough and protecting the heart. By MCI gel chromarography, silica gel chromatography and Sephadex LH-20 chromatography, thirty-one compounds were isolated from the ethanol extract of this plant. Based on spectroscopy method, all the compounds were elucidated as:ursolic acid (1), olieanic acid (2), uvaol (3), betulin (4), betulic acid (5), betulic-28-ethyl ester (6),3p,24-dihydroxyurs-12-en-28-oic acid (7), apigenin (8), apigenin-7-O-glucopyranoside (9), apigenin-7-O-galactopyranoside (10), luteolin (11), luteolin-7-O-glucoside (12), acacetin (13), acacetin-6"-glucuronide (14), gardenin B (15), scrophulein (16), salvigenin(17), isorhamnetin (18), tilianin (19), agastachoside (20), acacetin-7-O-glucoside-6"-O-malonyl ester (21), takakin-8-O-β-D-glucopyranoside (22), kaempferol (23), kaempferol-3-O-βD-(6"-O-p-coumaroyl)-galactopyranoside (24), kaempferol-3-O-β-D-(6"-O-p-coumaroyl)-glucopyranoside (25),2"-p-coumary lastra-galin(26), methyl rosmarinate (27), ethyl rosmarinate (28), stigmasterol (29), P-sitosterol (30), daucosterol (31). Compounds 10、27and 28 were isolated from the genus of Dracocepahlum for the first time,4、5、6 and 9 were isolated from this specie for the first time.
As a transcription factor, Nrf2 regulated the expression of phaseⅡand cellular detoxification enzymes, which could protect cells from radical and external toxic. Studies had shown that induction of Nrf2 expression was helpful for the treatment of a number of chronic diseases such as cardiovascular disease, diabetes. Some of the compounds we obtained were screened the Nrf2 inducing activity using a stable cell line which could express luciferase. Results showed that most flavonoids tested could induce of the expression of luciferase and could be potential Nrf2 activitors. This effect might be related to the heart and brain protection of D. moldavica.
Using HPLC method, the contents of tilianin and agastachoside in D. moldavica were determined. The flaconoids contents in different seasons of D. moldavica were compared. It indicated that the HPLC method was suitable for the quality evaluation of the herb.
香青兰(Dracocephalum moldavica L.)为一年生草本,维吾尔族和蒙古族习用药材,分布于黑龙江、吉林、辽宁、内蒙古、甘肃、山西、青海及新疆等省区,新疆南部有栽培,用于补脑安神,镇咳止喘,强心利尿。通过MCI柱色谱,硅胶柱色谱,Sephadex LH-20柱色谱从其地上全草乙醇提取物中分离得到7个三萜类成分,波谱学方法鉴定为：熊果酸(1),齐墩果酸(2),乌发醇(3),白桦酯醇(4),白桦酯酸(5),白桦酯醇-28-乙酯(6),3p,24-dihydroxyurs-12-en-28-oic acid(7)；26个黄酮类成分,鉴定为：洋芹素(8),洋芹素-7-O-β-D.葡萄吡喃糖苷(9),洋芹素-7-O-β-D-半乳吡喃糖苷(10),木犀草素(11),木犀草素-7-O-β-D-葡萄吡哺糖苷(12),金合欢素(13),acacetin-6"-glucuronide (14),栀子素乙(15),玄参黄酮(16),鼠尾草素(17),异鼠李素(18),田蓟苷(19),藿香苷(20),acacetin-7-O-glucoside-(6"-O-malonyl ester) (21), takakin-8-O-β-D-glucopyranoside (22),山柰酚(23),山柰酚-3-O-β-D-(6″-O-对羟基桂皮酰)-半乳吡喃糖苷(24),山柰酚-3-O-β-D-(6″-O-对羟基反式香豆酰基)-葡萄吡喃糖苷(25),2″-对羟基肉桂酰氧基黄芪苷(26)；苯丙素类化合物2个：迷迭香酸甲酯(27),迷迭香酸乙酯(28)；甾体类化合物3个：豆甾醇(29),p.谷甾醇(30),胡萝卜苷(31)。其中化合物10,27,28为首次从该属植物中分离得到,4,5,6,9为首次从该植物中分离得到。
Nrf2作为一种转录因子,调控了Ⅱ相酶和细胞解毒酶的表达,从而保护细胞免受自由基和外界毒物侵袭。研究表明,诱导Nrf2表达对于多种慢性疾病如心血管疾病、糖尿病的治疗均有帮助。我们对分离得到的部分化合物采用能表达荧光素的稳定细胞株进行了Nrf2诱导活性筛选,结构表明黄酮类化合物均有程度不同的诱导荧光素酶表达的作用,是潜在的Nrf2诱导剂。这种作用可能与香青兰保护心脑的功效有关。
我们选择了香青兰药材中两种黄酮苷类成分田蓟苷和藿香苷,建立了HPLC法同时测定药材中两种黄酮苷含量的方法,并且对不同采收季节的药材中两种黄酮苷的含量进行了考察,结果表明花期的香青兰田蓟苷及藿香苷含量较高,对进一步确定香青兰最佳采收期具有一定的参考意义。
Systematical study on the chemical constituents of traditional Chinese herbs is one of important routes to discover bioactive compounds. There are about 60 species belong to the genus Dracocephalum, family Labiatae. These plants distribute in alpine and semidry regions mainly in temperate Asia, with a few in Europe, one in North America. There are about 32 species,7 variations in China. Several species belong to the genus Dracocephalum are used as folk medicine for the treatment of tracheitis and cardiovascular disease in Xinjiang antonomous region. Dracocephalum moldavica can be applied for the protection of cardiac ischemia. This dissertation mainly focused on the chemical dtudies of the herbal plant. Bioactivities were investigated for some flavonoids. Determinations of tiliroside and agastachoside in D. moldavica were achieved by HPLC.
Dracocephalum moldavica L, habitually used herb by Weiwuer and Meng nationality, mainly distributed in Heilongjiang, Jilin, Liaoning, Neimenggu, Gansu, Shanxi, Qinghai and Xinjiang in China. It was an annual herb and was cultivated in southern Xinjiang autonomous region. The aerial parts of this herb were employed in smoothing the nerves, relieveing a cough and protecting the heart. By MCI gel chromarography, silica gel chromatography and Sephadex LH-20 chromatography, thirty-one compounds were isolated from the ethanol extract of this plant. Based on spectroscopy method, all the compounds were elucidated as:ursolic acid (1), olieanic acid (2), uvaol (3), betulin (4), betulic acid (5), betulic-28-ethyl ester (6),3p,24-dihydroxyurs-12-en-28-oic acid (7), apigenin (8), apigenin-7-O-glucopyranoside (9), apigenin-7-O-galactopyranoside (10), luteolin (11), luteolin-7-O-glucoside (12), acacetin (13), acacetin-6"-glucuronide (14), gardenin B (15), scrophulein (16), salvigenin(17), isorhamnetin (18), tilianin (19), agastachoside (20), acacetin-7-O-glucoside-6"-O-malonyl ester (21), takakin-8-O-β-D-glucopyranoside (22), kaempferol (23), kaempferol-3-O-βD-(6"-O-p-coumaroyl)-galactopyranoside (24), kaempferol-3-O-β-D-(6"-O-p-coumaroyl)-glucopyranoside (25),2"-p-coumary lastra-galin(26), methyl rosmarinate (27), ethyl rosmarinate (28), stigmasterol (29), P-sitosterol (30), daucosterol (31). Compounds 10、27and 28 were isolated from the genus of Dracocepahlum for the first time,4、5、6 and 9 were isolated from this specie for the first time.
As a transcription factor, Nrf2 regulated the expression of phaseⅡand cellular detoxification enzymes, which could protect cells from radical and external toxic. Studies had shown that induction of Nrf2 expression was helpful for the treatment of a number of chronic diseases such as cardiovascular disease, diabetes. Some of the compounds we obtained were screened the Nrf2 inducing activity using a stable cell line which could express luciferase. Results showed that most flavonoids tested could induce of the expression of luciferase and could be potential Nrf2 activitors. This effect might be related to the heart and brain protection of D. moldavica.
Using HPLC method, the contents of tilianin and agastachoside in D. moldavica were determined. The flaconoids contents in different seasons of D. moldavica were compared. It indicated that the HPLC method was suitable for the quality evaluation of the herb.
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