洋葱和洋葱籽化学成分的研究

【作者】 袁玲；

【导师】 苏亚伦； 陈若芸； 张东明；

【作者基本信息】 中国协和医科大学 ， 药物化学， 2008， 硕士

【摘要】 洋葱(Allium cepa.L)为百合科(Liliaceae)葱属(Allium L.)植物。在我国其鳞茎药食兼用,具有消炎抑菌、活血化瘀、止泻、防癌抗癌、利尿、降血糖、降血脂以及预防心血管疾病等功效。洋葱中含有的化学成分主要为硫化物、类黄酮、苯丙素酚类、甾体皂甙类、含氮化合物和前列腺素类等。洋葱籽是百合科葱属植物洋葱的种子,是维吾尔族传统用药,用于改善内脏各器官功能、通便、活血、治腹泻、受寒所引起的发烧、治中暑、消脸眼浮肿、预防流产、杀虫。目前洋葱籽的化学成分报道很少,而化学成分的药理活性尚未见报道。为了阐明该植物生物活性成分,更好的利用该属的药用植物资源,本课题组对洋葱籽和洋葱的化学成分和生物活性进行了研究。对洋葱籽和洋葱粗提物的初筛表明,洋葱籽的提取物在体外实验中具有明显的抑制PTP1B的作用;洋葱乙酸乙酯部位对胃癌细胞(BGC-823)有较强的细胞毒作用;洋葱冻干粉在香港中文大学筛选了降血脂药理活性,结果证实洋葱冻干粉可以有效降低血清总胆固醇及甘油三脂,可以改善低密度脂蛋白和高密度脂蛋白含量及两者比例。筛选结果提示洋葱籽和洋葱中可能含有降血糖、降血脂和抗癌的生物活性成分。从洋葱和洋葱籽中共分离得到34个化合物,并利用LC-MS~n的方法鉴定了正丁醇部位中的总皂苷,共确定了包括13个新的甾体皂苷类化合物在内的27个化合物的结构:天师酸(1),N-trans-feruloyl tyramine(2),β-sitosterol-3-β-glucopyranoside-6-palmitate(3),β-谷甾醇(4),胡萝卜苷(5),色氨酸(6),腺嘌呤核苷(7)以及14个皂苷类化合物(8-21):Alliofuroside A(8)和它的22位甲氧基化物(9),26-O-(β-D-葡萄糖)-22-O-甲基-(25R)-呋喃甾烷-5-烯-1β,3β,22α,26-四羟基1-O-α-L-鼠李糖-(1→2)-α-L-阿拉伯糖苷(10),26-O-(β-D-葡萄糖)-(25R)-呋喃甾烷-5-烯-1β,3β,22α,26-四羟基1-O-α-L-鼠李糖-(1→2)-α-L-阿拉伯糖苷(11),26-O-(β-D-葡萄糖)-(25R)-呋喃甾烷-5,20(22)-二烯-3β,26-二羟基3-O-β-D-葡萄糖基-(1→4)[α-L-鼠李糖基-(1→2)]-β-D-半乳糖苷(12),26-O-(β-D-葡萄糖)-(25S)-呋喃甾烷-5,20(22)-二烯-3β,26-二羟基3-O-β-D-葡萄糖基-(1→4)[α-L-鼠李糖基-(1→2)]-β-D-半乳糖苷(13),26-O-(β-D-葡萄糖)-(25R)-呋喃甾烷-5-烯-3β,22α,26-三羟基3-O-β-D-葡萄糖基-(1→4)[α-L-鼠李糖基-(1→2)]-β-D-半乳糖苷(14),26-O-(β-D-葡萄糖)-(25R)-呋喃甾烷-5-烯-3β,22α,26-三羟基3-O-β-D-葡萄糖基-(1→4)[α-L-鼠李糖基-(1→2)]-β-D-半乳糖苷(15),26-O-(β-D-葡萄糖)-(25S)-呋喃甾烷-5,22(23)-二烯-1β,3β,20α,26-四羟基1-O-α-L-鼠李糖基-(1→2)]-β-D-阿拉伯糖苷(16),26-O-(β-D-葡萄糖)-(25R)-呋喃甾烷-5,22(23)-二烯-1β,3β,20α,26-四羟基1-O-α-L-鼠李糖基-(1→2)]-β-D-阿拉伯糖苷(17),26-O-(β-D-葡萄糖)-(25R)-呋喃甾烷-5,20(22)-二烯-1β,3β,26-三羟基1-O-α-L-鼠李糖基-(1→2)]-β-D-阿拉伯糖苷(18),26-O-(β-D-葡萄糖)-(25S)-呋喃甾烷-5,20(22)-二烯-1β,3β,26-三羟基1-O-α-L-鼠李糖基-(1→2)]-β-D-阿拉伯糖苷(19),26-O-(β-D-葡萄糖)-(25S)-呋喃甾烷-5,20(22)-二烯-1β,3β,26-三羟基1-O-α-L-鼠李糖基-(1→2)]-β-D-半乳糖苷(20),26-O-(β-D-葡萄糖)-(25S)-呋喃甾烷-5-烯-1β,3β,22α,26-四羟基1-O-α-L-鼠李糖基-(1→2)]-β-D-半乳糖苷(21)(化合物1-21为从洋葱籽中分离得到);槲皮素(22)、槲皮素-4′-葡萄糖苷(23)、异鼠李素(24)、β-谷甾醇(4)、原儿茶酸(25)和槲皮素-3,4′-二-O-葡萄糖苷(26)(化合物4和22-26为从洋葱中分离得到);26-O-(β-D-葡萄糖)-(25R)-呋喃甾烷-5-烯-1β,3β,22α,26-四羟基1-O-α-L-鼠李糖基-(1→2)1-β-D-半乳糖苷(27)(化合物27为洋葱中未分离得到,但利用LC-MS~n鉴定了结构,利用此方法鉴定的另外5个化合物为8-11和21)。化合物1-9为已知化合物,化合物10-21和27为新化合物。化合物1-4为首次从该属植物中分离得到,化合物5、8、9为首次从该植物中分离得到。洋葱和洋葱籽中分离得到的部分单体进行了药理活性的筛选,所筛单体均未显示对PTP1B和一些肿瘤细胞的抑制活性;洋葱乙酸乙酯部位的黄酮(苷)显示了较强的抗氧化活性;这些单体的体外降血脂活性的筛选正在进行中。更多还原

【Abstract】 Onion（Allium cepa L.） is the plant of Allium L.of Liliaceae,it is a vegetable crop distributed all over China’s mainland and is used not only as food but also as medicine.It is claimed that red onion have a lot of bioactivities,such as eliminating inflammation, promoting blood flow,lowering blood fat and blood sugar,checking diarrhea,anticancer, diuresis,et al.There are diverse constituents in this plant,including sulfides,flavanoids, steroidal saponins,nitrogenous compound and prostanoids et al.The onion seeds are used as a traditional herb medicine of the Uygur（Uighur） nationality in Xinjiang,which can improve the functions of internal organs,treat diarrhoea,fervescence,calentura and puffiness of face and eye,promote blood flow,and prevent ectroma.Now,there is fewer report about the constituents of the onion seeds,and pharmacologycal reports about it has not been found in the world as well.In order to find the active principles from this medicinal plants,develop and utilize the resource of Chinese medicine,the project have investigated the chemical constituents and bioactivities of onion and its seeds.The preliminary screening of onion seeds and onion showed that onion seeds extract has conspicuous activity to inhibite the enzyme PTP1B in vitro,while the EtOAc extract of onion could inhibite the growth of BGC-823 in vitro;Another test was studied in Hongkong Chinese University for the hypolipidemic activity of freeze drying powder of onion,which indicated that it can lower total cholesterol and blood fat effectively and improve other blood fat indexs such as the content of LDL,HDL and their ratio.Above all,there may be some highly active compounds in lowering blood sugar,blood fat and anticancer in the plant of onion and its seeds.34 compounds have been isolated from the extract of onion and its seeds,and the LC-MSⁿ method has been applied to identify the gross saponins of the BuOH extract from onion.27 compounds,including 13 new steroidal saponins were identified as: Tianshi acid（1）,N-trans-feruloyl tyramine（2）,β-sitosterol-3β-glucopyranoside-6’-palmitate （3）,β-sit os terol（4）,daucosterol（5）,tryptophane（6）,adenine riboside（7）, Alliofuroside A（8）,22-OCH₃-alliofuroside A（9）,26-O-（β-D-glucopyranosyl）-22-O-methyl-（25R）-furost-5-en-1β, 3β,22α,26-tetrol 1-O-α-L-rhamnopyranosyl-（1→2）-α-L-arabinopyranoside（10）, 26-O-（β-D-glucopyranosyl）-（25R）-furost-5-en-1β,3β,22α, 26-tetrol 1-O-α-L-rhamnopyranosyl-（1→2）-α-L-arabinopyranoside（11）,26-O-（β-D-gl-ucopyranosyl）-（25R）-furost-5, 20（22）-dien-3β,26-diol 3-O-β-D-glucop- yranosyl-（1→4）-[α-L-rhamnopyranosyl-（1→2）]-β-D-galactopyranoside （12）,26-O-（β-D-glucopyranos- yl）-（25S）-furost-5,20（22）-dien-3β,26-diol 3-O-β-D-glucopyranos-yl-（1→4）-[α-L-rham nopyranosyl-（1→2）]-β-D-galactopyranoside（13）,26-O-（β-D-glucopyranosyl）-（25R）-furost-5-en-3β, 22α,26-triol 3-O-β-D-glucopyra-nosyl-（1→4）-[α-L-rhamnopyranosyl-（1→2）]-β-D-galactopyranoside （14）,26-O-（β-D-glucopyra- nosyl）-22-Omethyl-（25R）-furost-5-en-3β, 22α,26-triol3-O-β-D-glucopyranosyl-（1→4）-[α-L-rhamnopyranosyl-（1→2 ）]-β-D-galactopyranoside（15）,26-O-（β-D-glucopyranosyl）-（25S）-furost-5,22（23）-dien-1β, 3β,22α,26-tetrol 1-O-α-L-rhamnopyranosyl-（1→2）-α-L-arabinopyranoside（16）, 26-O-（β-D-glucopyranosyl）-（25R）-furost-5,22（23）-dien-1β,3β,22α,26-tetrol 1-O-α-L-rhamnopyranosyl-（1→2）-α-L-arabinopyranoside （17）,26-O-（β-D-glucopyranosyl）-（25R）-furost-5, 20（22）-dien- 1β,3β,26-triol 1-O-α-L-rhamnopyranosyl-（1→2）-α-L-arabi-nopyranoside （18）,26-O-（β-D-glucopyranosyl）-（25S）-furost-5,20（22）-dien-1β,3β,26-triol 1-O-α-L-rhamnopyranosyl-（1→2）-α-L-arabinopyranoside（19）,26-O-（β-D-gluco-pyranosyl）-（25S）-furost-5, 20（22）-dien-1β,3β,26-triol 1-O-α-L-rhamnopyranosyl-（1→2）-β-D-galactopyranoside（20）,26-O-（β-D-glucopyranosyl）-（25S）-furost-5-en-1β, 3β,22α,26-tetrol 1-O-α-L-rhamnopyranosyl-（1→2）-β-D-galactopyranoside（21） （Compounds 1-21 have been isolated from onion seeds）;quercetin（22）,quercetin-4′-O-glucopyranoside（23）,isorhamnetin（24）,β-sitosterol（4）,protecatechuic acid（25）, quercetin-3,4′-di-O-glucopyranoside（26）（Compounds 4 and 22-26 have been isolated from onion）;26-O-（β-D-glucopyranosyl）-（25R）-furost-5-en-1β,3β,22α,26- tetrol 1-O-α-L-rhamnopyranosyl-（1→2）-β-D-galactopyranoside（27）（Compound 27 have not been isolated from onion,but its structure have been identified by LC-MSⁿ method,as well as compounds 8-11 and 21）.Compounds 1-9 were known compounds,Compounds 10-21 and 27 were new compounds;compounds 1-4 were isolated from the genus Allium for the first time,compounds 5-7 were isolated from this plant for the first time.The screened compounds from onion and onion seeds showed no effect to inhibite the enzyme PTP1B and no cytotoxicity to some tumor cells such as HCT-8,Bel-7402, BGC-823,A549 and A2780;The flavonoid（glycoside） from the EtOAc extract of onion showed strong antioxygen activity;All these compounds are in the screening of hypolipidemic activity in vitro.更多还原