The isolation and identification of anticancer compounds targeting nuclear receptor from leaves of Magnolia biloba and seeds of Camellia oleifera

靶点药物研究已成为现代新药研究与开发的潮流，而核受体被发现与多种重大疾病特别是癌症的发生发展关系密切，并已被确认是一种理想的药物靶标。孤儿核受体TR3/Bcl-2凋亡途径及tRXRα/p85信号转导通道是本研究团队近年来发现的两条独特的癌细胞凋亡调控通路。寻找靶向并调控这些核受体信号通路的小分子药物将能特异有效的抑制肿瘤细胞的生长，十分具有开发成新型靶向抗癌药物的潜力。我们前期科研成果的基础上，建立生物活性筛选模型，对两种有靶向核受体发挥抗癌作用潜力的厚朴叶及油茶籽的醇提物进行的更细致的化学成分分离与化学结构鉴定。研究共从厚朴叶获得化合物11个，通过核磁及质谱分析鉴定为：厚朴酚(1)、和厚朴酚...The study of the targeted drugs has become the new trend of the new drug development and study, and the nuclear receptor is reported of a near relationship of many diseases. It has been ensured of an ideal drug target which is related to many diseases. The apoptosis pathway of orphan nuclear receptor TR3/Bcl-2 and the tRXRα/p85 signaling transduction pathway are the unique regulatory pathways that...学位：医学硕士院系专业：药学院_药物化学学号：3232012115309

Research of pharmacological effect basis of usual clinical medications with camellia oil

目的探讨茶油多种临床用药可能的药理药效基础。方法将油茶籽经两次95%的乙醇回流提取后浓缩至不含乙醇和水的提取物,取其中的茶油部分作为试验药物;用肿瘤坏死因子-α(Tnf-α)处理人乳腺癌细胞系(MCf-7)细胞建立细胞炎症模型,进一步用蛋白质印迹技术观察药物处理对细胞炎症因子Iκb-α表达的影响进而评价茶油是否具有抗炎活性。结果从油茶籽提取得到的茶油显著地抑制细胞中Tnf-α诱导的Iκb-α的降解从而抑制炎症发生。结论茶油对细胞显示良好的抗炎作用,这种特性可能是其临床应用于治疗皮肤过敏、暗疮、疥癣、小儿红屁股、以及皮肤烧烫伤等多种与炎症相关疾病的药理基础之一。Objective To explore the possible pharmacological effect basis of usual clinical medications with camellia oil.Methods After twice 95% ethanol reflux extraction of camellia seed, the solution was concentrated to the extractive without ethanol and water.Camellia oil in the extractive was taken as study drug.Human breast adenocarcinoma cell line(MCF-7) cell was managed by tumor necrosis factor(TNF)-α to build a cell inflammation model.Influence of drug treatment on cell inflammatory cytokines IκB-α was observed by Western blot, in order to make evaluation on whether camellia oil possesses anti-inflammatory activity.ResultsCamellia oil extracted from camellia seed had significantly inhibiting effect on degradation of IκB-α induced by TNF-α, so as to suppress occurrence of inflammation.Conclusion Camellia oil has precise anti-inflammation effect on cells, and this effect may be one of its pharmacological basis for treating inflammation related diseases as skin allergy, pimples, scabies, pediatric bunda vermelha, skin burn and scald.厦门市科技计划项目(项目编号:3502Z20123015); 国家自然科学基金(项目编号:81102332

Chemical component in camellia cake against ultraviolet rays radiation damage on skin cells

目的分离纯化油茶粕中抗皮肤细胞紫外损伤活性成分。方法硅胶色谱和高效液相反相制备色谱纯化油茶粕正丁醇提取物,WESTErn-blOTTIng法检测纯化物质对uV照射HA CA T皮肤细胞Jnk、P38激活以及MMP-9的表达的影响。结果分离得到一单体化合物,经鉴定为kAEMPfErOl 3-O-{β-d-gluCOPyrAnOSyl-(1->2)-[α-l-rHAMnOPyrAnOSyl-(1->6)]-β-d-gluCOPyrAnOSIdE},且该化合物能够抑制HA CA T皮肤细胞uV照射后Jnk、P38激活以及MMP-9表达。结论油茶粕含有抗皮肤细胞紫外损伤活性成分,值得进一步开发。Objective To isolate the chemical component of camellia cake against ultraviolet rays radiation damage on skin cells.Methods Silica gel column chromatography and reverse phase preparative HPLC were used for the isolation of active compounds from the n-butanol extract of camellia cake.The effects of isolated compound on the activation of JNK and P38,and the protein expression of MMP-9 in UV irradiated Ha Ca J skin cells were determined by western blotting assay.Results A flavonoid glycoside was isolated from the camellia cake and identified as Kaempferol 3-O-{ β-D-glucopyranosyl-( 1-> 2)-[α-L-rhamnopyranosyl-( 1-> 6) ]-β-D-glucopyranoside} using NMR dada analysis.In addition,the isolated compound was showed to markedly inhibit the activation of JNK and P38,and MMP-9 protein expression in UV irradiated Ha Ca J skin cells.Conclusion The components in camellia cake might have significant activity on protecting skin from UV rays radiation damage,suggesting their potential development values.国家自然科学基金(No.81102332); 福建省厦门市科技计划项目(No.3502Z20123015