【作者】 王丹；

【导师】 贾琦； 李医明；

【作者基本信息】 上海中医药大学 ， 中药学， 2019， 硕士

【摘要】 桂枝Cinnamomi ramulus为樟科植物肉桂Cinnamomum cassia Presl的干燥嫩枝,主产于广东、广西、云南等省区。现代药理研究表明,具有缓和肠胃刺激、强心、改善微循环、抗炎、抗血小板凝集等多种生理活性。桂枝为临床常用中药,以桂枝为主药的经典方剂,多用于风寒感冒、脘腹冷痛、血寒经闭、关节痹痛、痰饮、水肿、心悸、奔豚等病症[1]。目前国内外学者对桂枝的化学成分研究多集中在挥发油部位,对其非挥发油部位的化学成分研究报道较少。桂枝作为临床用药,多以水煎为主,说明有必要对桂枝中其它部位特别是较大极性化学成分进行研究。为进一步阐明桂枝化学成分,本课题采用硅胶、凝胶及大孔树脂柱色谱、制备高效液相色谱等现代分离方法和技术对其化学成分进行了系统分离,并根据波谱数据结合理化性质进行了结构鉴定。目前,从桂枝中共分离鉴定38个化学成分,即从乙酸乙酯萃取部位分离鉴定16个化合物(化合物1~16),从正丁醇萃取部位分离鉴定12个化合物(化合物17~28),从二氯甲烷萃取部位分离鉴定10个化合物(化合物29~38),分别为:二氢红花菜豆酸(1),rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo[3,2,1]-oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid(2),3-甲氧基-4-羟基苯甲酸(3),4-羟基-3,5-二甲氧基苯甲酸(4),对羟基苯甲酸(5),反式肉桂酸(6),反式邻羟基肉桂酸(7),erythro guaiacylglycerol-8′-vanillic acid ether(8),桂枝酸A(9),邻羟基苯甲酸(10),decumbic acid(11),苯丙三醇(12),邻羟基苯丙酸(13),原儿茶酸(14),邻香豆酸葡萄糖苷(15),cryptamygin B(16),百秋李醇(17),络塞维(18),二氢络塞维(19),graphostromane B(20),(+)-lyoniresinol-3a-O-β-D-glucopyranoside(21),(-)-lyoniresinol-3a-O-β-D-glucopyranoside(22),cinnacaside(23),subaveniumin A(24),肉桂醇-6’-O-α-呋喃阿拉伯糖基-O-β-吡喃葡萄糖苷(25),2-苯乙基-1-O-β-D-葡萄糖-α-L-吡喃阿拉伯糖苷(26),cinnacasol(27),((2R,3S,4S,5R,6R)-6-(benzyl-oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl hydrogen sulfate(28),松柏醛(29),邻甲氧基苯甲酸(30),(2R,3R)-5,7-二甲氧基-3’,4’-亚甲二氧基黄烷醇(31),反式肉桂醇(32),反式邻甲氧基肉桂醇(33),2-羟基苯丙醇(34),cinnamomulactone(35),(+)-syringaresinol(36),cinnamomumolide(37),cinnacassin L(38)。其中化合物9、19为新化合物,化合物1、2、4、8、10~13、17、20~22、24~26、28、31、33、34共计19个化合物为首次从桂枝中分离得到。从化学结构看,化合物1、2、17、20、23,27为萜类化合物;3~16、18、19、21、22、24、25、29、30、32~38为苯丙素或酚酸类化合物;31为黄酮类化合物;26与28为其他类化合物。这些化合物中除15、16、18、19、21~23、25、26、28为糖苷类化合物外,其余均为苷元。针对桂枝药理作用及教研组拥有药理活性筛选平台,取前期分离鉴定的24个化合物(1~7,9~25)采用PA诱导的心肌细胞损伤模型及胰岛β细胞损伤模型分别进行了活性的初步筛选。结果显示,与模型组相比,所筛24个化合物在20μM浓度下,对PA诱导的心肌细胞损伤均无显著保护作用;但与模型组相比,化合物13、20、23、25在50μM浓度下对PA诱导的胰岛β细胞损伤有显著保护作用。更多还原

【Abstract】 Cinnamomi ramulus is a dried twig of Cinnamomum cassia Presl,which is mainly produced in Guangdong,Guangxi and Yunnan provinces.Modern pharmacological studies show that the herb has a variety of physiological activities such as relieving gastrointestinal irritation,cardiotonic,improving microcirculation,anti-inflammation,anti-platelet aggregation,etc.It is one of the commonly used traditional Chinese medicines.A series of classic prescriptions with Cinnamomi ramulus as the main medicine are in clinical practice,which are mostly used for anemofrigid cold,abdominal cold-pain,amenorrhea due to blood cold,arthralgia of joint,phlegm retention,edema,palpitation,renal mass and other diseases[1].At present,scholars over the world have focused on the chemical constituents of the volatile oils in Cinnamomi ramulus,and have little research on the chemical constituents of its non-volatile oils.As a clinical herb medicine,water decoction is commonly used,demonstrating that it is necessary to study the chemical constituents of other parts,especially the larger polar parts.In order to further reveal the chemical components of Cinnamomi ramulus,silica gel,Sephadex LH-20 column and sp-HPLC chromatographies were applied to separate and purify the chemical constituents,followed by various spectral analyses to determine the chemical structures.A total of 38 compounds were isolated from Cinnamomi ramulus,among which 16 compounds(1-16)are from Et OAc extract,12 compounds(17-28)from n-Bu OH extract and 10 compounds(29-38)from dichloromethane extract.Their structures were identified as dihydrophaseic acid(1),rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo[3,2,1]-oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid(2),vanillic acid(3),syringic acid(4),4-hydroxybenzoic acid(5),E-cinnamic acid(6),E-O-hydroxycinnamic acid(7),erythro guaiacylglycerol-8′-vanillic acid ether(8),guizhi acid A(9),salicylic acid(10),decumbic acid(11),1-phenyl-1,2,3-propanetriol(12),hydrocoumaric acid(13),protocatechuic acid(14),E-melilotoside(15),cryptamygin B(16),patchoulol(17),rosavin(18),dihydrorosavin(19),graphostromane B(20),(+)-lyoniresinol-3a-O-β-D-glucopyranoside(21),(-)-lyoniresinol-3a-O-β-D-glucopyranoside(22),cinnacaside(23),subaveniumin A(24),rosarin(25),2-phenylethyl-β-vicianoside(26),cinnacasol(27),((2R,3S,4S,5R,6R)-6-(benzyloxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl hydrogen sulfate(28),coniferyl aldehyde(29),O-anisic acid(30),(2R,3R)-5,7-dimethoxy-3’,4’-methylenedioxyflavan-3-ol(31),E-cinnamic alcohol(32),trans-2-methoxycinnamyl alcohol(33),3-(O-hydroxyphenyl)propanol(34),cinnamomulactone(35),(+)-syringaresinol(36),cinnamomumolide(37),cinnacassin L(38).Among them,two compounds,viz.,9 and 19,are new compounds,and 19 compounds,namely,1,2,4,8,10-13,17,20-22,24-26,28,31,33 and 34 are isolated from the plant for the first time.Structurally,compounds 1,2,17,20,23 and 27 could be classified as terpenoids,3-16,18,19,21,22,24,25,29,30 and 32-38 are phenylpropanoids or phenolic acids,31 is flavonoids,26 and 28 are other compounds.Among these compounds,15,16,18,19,21-23,25,26 and 28 are glycosides,while the rests are aglycones.According to the pharmacological function of Cinnamomi ramulus and the available platform at our laboratory,24 compounds(1-7,9-25)isolated and identified in the early stage were tested on the PA-induced injury model of cardiomyocytes and islet β cells.The results showed that the 24 compounds at the concentration of 20 μM had no significant protective effects compared with the group of PA-induced injury model of cardiomyocytes,while the compounds 13,20,23 and 25 had significant protective effect at 50 μM compared with the group of PA-induced injury model of islet β cells.更多还原