桂枝中化学成分及抗肿瘤和抗炎活性研究  

Study on chemical constituents, antitumor and anti-inflammatory activities of Cinnamomi Ramulus

作　　者：钱纯果 金路 朱龙平[1,2] 周洋 黎润南 杨得坡 徐新军[1,2] 赵志敏 QIAN Chun-guo;JIN Lu;ZHU Long-ping;ZHOU Yang;LI Run-nan;YANG De-po;XU Xin-jun;ZHAO Zhi-min(School of Pharmaceutical Science,Sun Yat-Sen University,Guangzhou 510006,China;Guangdong Technology Research Center for Advanced Chinese Medicine,Guangzhou 510006,China;Deqing County Dexin Agricultural Development Co.,Ltd.,Zhaoqing 526600,China)

机构地区：[1]中山大学药学院,广东广州510006 [2]广东省现代中药工程技术研究开发中心,广东广州510006 [3]德庆县德鑫农业发展有限公司,广东肇庆526600

出　　处：《中草药》2022年第1期31-40,共10页Chinese Traditional and Herbal Drugs

基　　金：广东省农业科技创新及推广体系建设项目(2021KJ268,2021KJ142,2020KJ142);广东省重点领域研发计划(2020B020221002,2020B1111110003)。

摘　　要：目的对桂枝Cinnamomi Ramulus中非挥发性化学成分及其抗肿瘤、抗炎活性进行研究。方法运用D101大孔吸附树脂、正反相硅胶、SephadexLH-20以及半制备HPLC等多种色谱方法进行分离纯化,并根据其波谱数据鉴定出化合物的结构;通过测定化合物对脂多糖(lipopolysaccharide,LPS)诱导小鼠RAW 264.7巨噬细胞释放一氧化氮(NO)的抑制能力,并采用MTT法考察其对人乳腺癌MDA-MB-231细胞的体外抑制能力,进而评价化合物的抗炎和抗肿瘤活性。结果从桂枝甲醇提取物中共分离得到21个化合物,分别鉴定为表儿茶素(1)、2-(3,4-二羟苯基)乙基-β-D-吡喃葡萄糖苷(2)、3,5-二羟苯基-乙醇-3-O-β-吡喃葡萄糖苷(3)、staphylionoside D(4)、glochidionionoside C(5)、柑橘苷A(6)、dendranthemoside A(7)、euodionoside G(8)、euodionoside F(9)、3,4,5-三甲氧苯基-1-O-β-D-呋喃芹糖-(1′′→6′)-β-D-吡喃葡萄糖苷(10)、淫羊藿次苷D1(11)、淫羊藿次苷F2(12)、(+)-lyonirenisol-3a-O-β-D-glucopyranoside(13)、l-threo-guaiacylglycerol-8-O-β-glucopyranoside(14)、邻甲氧基肉桂醛(15)、肉桂醛(16)、肉桂酸(17)、4-羟基-3-甲氧基肉桂醛(18)、邻甲氧基苯甲酸(19)、(2R,3R)-5,7-二甲氧基-3′,4′-亚甲二氧基黄烷醇(20)、苯甲酸(21)。其中,化合物1、20为黄酮类化合物,2、3、10~12为芳香苷类化合物,4~9为降倍半萜苷类化合物,13、14为苯丙素苷类化合物,15~18为苯丙素类化合物,19、21为苯甲酸类化合物。抗炎、抗肿瘤活性筛选结果表明,化合物15可以有效降低MDA-MB-231细胞的存活能力,其半数抑制浓度(medianinhibitionconcentration,IC50)为(34.11±3.42)μmol/L。化合物15、16、18、20对LPS诱导RAW264.7细胞释放NO具有一定的抑制作用,其IC50分别为(5.27±0.62)、(7.98±2.41)、(7.91±0.81)、(70.34±3.07)μmol/L。结论化合物2~10、12、14首次从桂枝中分离得到,其中化合物3、5~9、14首次从樟科植物中分离得到,化合物4首次从樟属�Objective To investigate the chemical constituents, antitumor and anti-inflammatory activities of extracts from the non-volatile component of Guizhi(Cinnamomi Ramulus). Methods The compounds were isolated and purified by various chromatographic techniques, including D101, silica gel, Sephadex LH-20 and semi-preparative HPLC, and their structures were identified based on combining spectral analysis with chemical evidence. Their potential anti-tumor and anti-inflammatory effects were evaluated on human breast cell line(MDA-MB-231) and murine macrophage cell line(Raw264.7), respectively. Results A total of 21 compounds were isolated from the methanol extract of C. Ramulus and identified as epicatechin(1),2-(3,4-dihydroxyphenyl)ethyl-β-D-glucopyranoside(2), 3,5-dihydroxyphenethyl alcohol 3-O-β-glucopyranoside(3), staphylionoside D(4), glochidionionoside C(5), citroside A(6), dendranthemoside A(7), euodionoside G(8), euodionoside F(9),3,4,5-trimethoxyphenyl-1-O-β-D-apiofuranosyl-(1′′→6′)glucopyranoside(10), icariside D1(11), icariside F2(12),(+)-lyonirenisol-3 a-O-β-D-glucopyranoside(13), l-threo-guaiacylglycerol-8-O-β-glucopyranoside(14), O-methoxy cinnamaldehyde(15), cinnamaldehyde(16), cinnamic acid(17), 4-hydroxy-3-methoxycinnamaldehyde(18), O-anisic acid(19),(2 R,3 R)-5,7-dimethoxy-3′,4′-methylenedioxyflavan-3-ol(20), and benzoic acid(21). Compounds 1 and 20 were flavonoids, 2—3 and 10—12 were aromatic glycosides, 4—9 were norsesquiterpenoid glycosides, 13—14 were phenylpropanoid glycosides, 15—18 were phenylpropanoids, and 19 and 21 were phenolic acids. Anti-inflammatory and anti-tumor assays in vitro showed that compound 15 effectively reduced the viability of MDA-MB-231 cells with IC50 of(34.11 ± 3.42) μmol/L. Compounds 15—16, 18 and 20 inhibited releases of NO induced by LPS from RAW 264.7 cells with IC50 of(5.27 ± 0.62),(7.98 ± 2.41),(7.91 ± 0.81), and(70.34 ± 3.07)μmol/L respectively. Conclusion Compounds 2—10, 12, and 14 are isolated from this plant for the first time.

关 键 词：桂枝 肉桂醛 邻甲氧基肉桂醛 肉桂酸 抗炎 抗肿瘤 

分 类 号：R284.1[医药卫生—中药学]