Two New Phenylpropanetriol Glycosides in the Fruits of Melia toosendan

Two new phenylpropanetriol glycosides, named as meliadanoside A (3 - methoxy- 5 - hydroxy-9- (1' - O-β-D-glucopyranosyl) - threo - phenylpropanetriol ) and meliadanoside B (4- hydroxy-7, 8- (2', 1' - O- β- D -glucopyranosyl) - phenylpropanetriol), were isolated from the water-soluble extract of the fruits of Meliatoosendan Sieb. et Zucc., along with threo-guaiacylglycerol. Their structures were elucidated by spectroscopic and chendcal analysis.

Two new limonoids from Melia toosendan

Two new limonoid-type triterpenoids, named 12-o-ethyl-l-deacetylnimbolinin B and 1-o-tigloyl-1-o-debenzoylohchinal, have been isolated from the fruit of Melia toosendan Sieb. et Zucc. Their structures were elucidated by spectral methods, including 2D-NMR spectra.

New limonoids from the fruits of Melia toosendan

Two new limonoids,1α-tigloyloxy-3α-acetoxyl-7α-hydroxyl-12α-ethoxyl nimbolinin（1） and lα-benzoyloxy-3α-acetoxyl-7α- hydroxyl-12α-ethoxyl nimbolinin（2）,were isolated from the fruits of Melia toosendan.Their structures were established on the basis of various NMR spectroscopic analyses,including 2D-NMR techniques（HSQC,HMBC,NOESY） and HR-ESI-MS.

Anticancer Effects of Crude Extract from Melia toosendan Sieb.et Zucc on Hepatocellular Carcinoma In Vitro and In Vivo

Objective： To investigate the anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc and its possible molecular mechanisms in vitro and in vivo. Methods： Transonic alcohol-chloroform extraction method was used to extract toosendanin from the bark of Melia toosendan Sieb. et Zucc, and the content of toosendanin in the crude extract was measured by high performance liquid chromatography （HPLC）. Anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc were investigated in in vivo and in vitro studies. In the in vitro experiment, human hepatocellular carcinoma cell lines SMMC-7721 and Hep3B were co-incubated with toosendanin crude extract of different concentrations, respectively. In the in vivo experiment, BALB/c mice were subcutaneously inoculated with mouse hepatocellular carcinoma H22 cells and treated with crude extract. Results： HPLC revealed the content of toosendanin was about 15%. Crude extract from Melia toosendan Sieb. et Zucc inhibited cancer cells growth in a dose- and time-dependent manner. The 50% inhibitory concentration （IC50, 72 h） was 0.6 mg/L for SMMC-7721 cells and 0.8 mg/L for Hep3B cells. Both high-dose [0.69 mg/（kg·d）] and low-dose [0.138 mg/（kg·d）] crude extract could markedly suppress cancer growth, and the inhibition rate was greater than 50%. Hematoxylin and eosin staining showed necrotic area in cancers and transmission electron microscopy displayed necrotic and apoptotic cancer cells with apoptotic bodies. Immunohistochemistry showed that the expression of Bax and Fas increased and the expression of Bcl-2 reduced. Conclusions： Toosendanin extract has potent anti-cancer effects via suppressing proliferation and inducing apoptosis of cancer cells in vivo and in vitro. The mechanism of apoptosis involves in mitochondrial pathway and death receptor pathway.

Two new limonoids isolated from the fuits of Melia toosendan

In the present study, two new limonoids, 1α, 7α-dihydroxyl-3α-acetoxyl-12α-ethoxylnimbolinin(1) and 1α-tigloyloxy-3α-acetoxyl-7α-hydroxyl-12β-ethoxylnimbolinin(2), together with other four known limonoids(3-6), were isolated from the fruits of Melia toosendan. Their structures were elucidated by means of extensive spectroscopic analyses(NMR and ESI-MS) and comparisons with the data reported in the literature. The isolated compounds were evaluated for their antibacterial activities. Compound 4 exhibited significant antibacterial activity against an oral pathogen, Porphyromonas gingivalis ATCC 33277, with an MIC value of 15.2 μg·m L-1. Compound 2 was also active against P. gingivalis ATCC 33277, with an MIC value of 31.25 μg·m L-1. In conlcusion, our resutls indicate that these compounds may provide a basis for future development of novel antibiotics.

New limonoids isolated from the bark of Melia toosendan

Two new limonoids, 12-ethoxynimbolinins G and H(compounds 1 and 2), and one known compound, toosendanin(Chuanliansu)(compound 3), were isolated from the bark of Melia toosendan. Their structures were elucidated by spectroscopic analysis and X-ray techniques. The absolute configuration of toosendanin(3) was established by single-crystal X-ray diffraction. Compounds 1-3 were evaluated for their cytotoxicity against five tumor cell lines.

Based on network pharmacology to explore the mechanism of hepatotoxicity of Fructus Meliae Toosendan

Objective:To explore the potential mechanism of hepatotoxicity induced by Fructus Meliae Toosendan(FMT)through network pharmacology.Methods:The active components and targets of FMT were identified and screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database,PubChem Database and Swiss Target Prediction database,etc.Genecards,pharmGKB,and OMIM databases were used to collect relevant targets of hepatotoxicity,and intersect them with the targets of active ingredients to obtain the potential targets of hepatotoxicity caused by FMT.A compound-target network was constructed with Cytoscape 3.8.0 software.The String 11.0 database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted by R software,and then the pathways directly related to hepatotoxicity were integrated.Results:In this study,9 active ingredients of FMT and 265 targets were obtained.There are 533 hepatotoxicity-related targets,and 76 potential targets for hepatotoxicity caused by FMT,among which quercetin,melianone,and nimbolin A are the key active components for hepatotoxicity caused by FMT,and MYC,STAT3,JUN,and RELA were the core target proteins of FMT’s hepatotoxicity.There were 2353 GO entries(P<0.05),including 2181 Biological Process(BP),41 Cellular Component(CC)and 131 Molecular Function(MF).KEGG enrichment analysis revealed 165 pathways(P<0.05),of which Th17 cell differentiation,HIF-1 signaling pathway,PI3K-Akt signaling pathway were strongly correlated with the hepatotoxicity of FMT.Conclusion:Through network pharmacology,it was found that many potential components in azadirachia chinaberry may be involved in the regulation of apoptosis,excessive inflammatory response and mitochondrial dynamics through multi-target and multi-pathway,resulting in the generation of hepatotoxicity.

基于网络药理学探讨川楝子治疗急性髓细胞性白血病的作用靶点与机制

目的基于网络药理学及生物信息方法,分析川楝子治疗急性髓细胞性白血病(AML)的可能作用靶点与分子机制。方法通过TCMSP、Drugbank、Uniprot、SwissTargetPrediction等数据库分别获取川楝子与AML的相关靶点,经韦恩分析获取川楝子作用于AML的潜在靶点,并结合KEGG和GO分析,探讨川楝子发挥抗AML的作用机制;基于STRING数据库构建蛋白互作网络图,筛选其核心作用基因,采用分子对接技术分析小分子药物与疾病核心靶点的作用方式,并通过GEPIA数据库分析与患者预后密切相关的蛋白。结果网络药理学分析发现,川楝子可能通过作用于185个蛋白发挥抗AML的作用;GO分析和KEGG通路富集分析提示,川楝子通过影响细胞凋亡等生物过程,以及调控PI3K-Akt和MAPK等信号通路,影响AML的发生和发展;川楝子的有效成分与6个核心蛋白靶点均具有一定的结合活性,靶向作用于这些核心蛋白靶点可发挥抗AML的作用;GEPIA数据库分析发现人原癌基因酪氨酸蛋白激酶(proto-oncogene tyrosine-protein kinase Src,SRC)基因的表达与AML患者的预后密切相关,低表达SRC的患者预后较好,可能是川楝子抗AML的潜在作用靶点之一。结论川楝子中的有效成分可通过调控多靶点蛋白影响细胞凋亡,调控PI3K-Akt、MAPK信号分子等多种途径发挥抗AML的作用,SRC可能成为川楝子改善AML预后的潜在作用靶点之一。

基于网络药理学系统评价川楝子治疗肝癌的作用机制

基于网络药理学研究方法,利用SymMap数据库获得川楝子治疗肝癌的化学成分及靶点基因,从GeneCards数据库获取疾病靶点基因,将川楝子和肝癌的交集靶点导入GeneMANIA数据库获得靶点互作关系,并进行GO和KEGG通路富集分析,结合关键靶点基因在肝癌组织中的表达与预后的相关性分析,筛选到槲皮素等6种主要活性成分,TP53、AKT1、IGF2、CDKN2A等主要靶点,癌症通路、癌症中蛋白聚糖、PI3K-Akt信号通路、乙肝和大肠癌通路等主要调控路径,揭示了川楝子治疗肝癌的机制具有多成分、多靶点和多通路的性质,从整体上为川楝子治疗肝癌提供参考。

川楝子中三萜类化学成分的研究

目的研究川楝果实的三萜类化学成分。方法运用硅胶柱色谱和十八烷基硅烷键合硅胶(ODS)反相柱色谱对川楝子的乙酸乙酯萃取部位进行分离纯化,通过理化方法和波谱数据分析鉴定化合物结构。结果从川楝子中分离并鉴定了5种化学成分,分别为(21S,23R,24R)-21,23-epoxy-21,24-dihydroxy-25-methoxytirucall-7-en-3-one(化合物1),Cinamodiol,Meliasenin G,21R,23R-epoxy-21α-ethoxy-24S,25-dihydroxy-apotirucall-7-en-3-one,Toosendine E。结论得到的化合物均为甘遂烷型的三萜类化合物,其中化合物1为首次从川楝果实中分离得到。

川楝柠檬苦素类化学成分及其细胞毒活性研究

目的:研究川楝Melia toosendan Sieb.et Zucc.果实中的柠檬苦素类化学成分及其细胞毒活性。方法:采用硅胶、ODS、Sephadex LH-20葡聚糖凝胶等多种柱色谱分离技术对川楝果实90%乙醇提取物进行分离纯化,并根据理化性质和波谱数据鉴定化合物结构,利用MTT法测定10个化合物对不同肿瘤细胞的细胞毒活性。结果:从川楝果实的醇提物中分离得到10个柠檬苦素类化合物,分别鉴定为:sendanin(1)、1,7-diacetylsendanin(2)、1-acetylsendanin(3)、7-acetylsendanin(4)、pentaol(5)、meliarachin C(6)、12-O-acetylazedarachin B(7)、azedarachin B(8)、川楝素(9)、meliatoosenin D(10)。10个化合物对5株肿瘤细胞的体外增殖具有不同程度的抑制作用。结论:其中,化合物2~6为首次从该植物中分离得到,且化合物6、9、10对人胃癌细胞MGC803和人结肠癌细胞COLO205表现出较强的细胞毒活性。

川楝子的化学成分研究

目的研究川楝子的化学成分。方法采用硅胶、凝胶柱色谱等方法对川楝子的化学成分进行分离,运用波谱分析技术和理化常数对照等方法对化合物结构进行鉴定。结果分离鉴定了16个化合物,分别鉴定为表松脂醇(1),clema- phenol A(2),medioresinol(3),(±)balanophonin(4),evofolin-B(5),槲皮素(6),异槲皮苷(7),芦丁(8),阿魏酸(9),对羟基苯甲醛(10),松柏醛(11),丁香酸(12),异香草酸(13),对羟基苯甲酸(14),5-羟甲基糠醛(15)和cirsiumaldehyde(16)。结论化合物6为首次从川楝子中分离得到,其余化合物均为首次从楝属植物中分离得到。

川楝子不同提取部位药效及毒性的比较研究

目的:探讨川楝子不同提取部位的部分药效和急性毒性作用。方法:采用冰乙酸或甲醛致痛复制小鼠疼痛模型,角叉菜胶致足肿胀和二甲苯致耳肿胀等炎症模型,对川楝子的乙酸乙酯提取物、石油醚提取物、80%乙醇提取物及水提取物的镇痛和抗炎等作用进行了研究。结果:川楝子乙酸乙酯提取物40 g/kg剂量能显著抑制冰乙酸所致小鼠扭体反应和甲醛所致鼠足疼痛反应,减轻二甲苯诱导的小鼠耳廓肿胀度,并可显著增加小鼠的睾丸重量,减轻其体重;川楝子乙醇提取物20 g/kg剂量组能显著降低角叉菜所致诱导的小鼠足肿胀程度及二甲苯诱导的耳廓肿胀度;川楝子石油醚提取物对甲醛所致的疼痛反应有明显的抑制作用,同时还可显著增加小鼠睾丸和肾上腺指数;川楝子水提物无明显镇痛和抗炎作用。测得小鼠灌服川楝子乙酸乙酯提取物的LD50为82.85 g/kg。未测出其它溶媒提取物对小鼠的LD50,测得小鼠灌胃川楝子石油醚提取物、酒精提取物及水提物的最大耐受量分别为:133.2 g/kg,122.0 g/kg,52.0 g/kg。在此剂量下各组动物均未出现明显异常。结论:川楝子乙酸乙酯提取物具有显著的抗炎和镇痛作用,同时也有较强的急性毒性作用;提示川楝子的有效成分可能在乙酸乙酯提取物部分,其毒性成分和有效物质可能为同一类物质。

超声波提取川楝素的方法研究

运用超声波技术从川楝树韧皮中提取川楝素,并与常规方法进行了比较,超声波提取川楝素具有省时、节能、提取率高等优点.实验条件:超声波协助提取法的最佳工艺参数为:固液比为1/20,提取时间为30 min,提取3次.在优化条件下,川楝素的提取率为3.25 mg·g-1.

川楝子总黄酮和多糖提取及其抗氧化活性研究

研究了川楝子总黄酮和多糖的最佳提取条件,并利用过硫酸铵/N,N,N,,N′-四甲基乙二胺(AP-TEMED)反应体系和Fenton反应体系测其提取成分的抗氧化活性。结果表明,川楝子总黄酮提取的最佳工艺条件为:70%(体积分数)乙醇,料液比1∶30(g∶mL),微波提取7.5 min;其多糖提取的最佳工艺条件为:浸提3 h,料液比1∶15(g∶mL),提取4次。川楝总黄酮和多糖均具有较强的抗氧化活性。当总黄酮质量浓度为9.74 g/L时,对超氧阴离子自由基(O2-.)的清除效率达到76.6%,其质量浓度为12.38 g/L时,对羟基自由基(.OH)的清除效率可达到84.0%;当多糖质量浓度达到10 g/L时,对O2-.的清除效率达到63.7%,对.OH的清除效率可达到74.0%。

反相高效液相色谱法测定川楝树皮中的川楝素

A new method for the determination of toosendanin in the bark of Melia toosendan sieb.et zucc.by reversed-phase high performance liquid chromatography（RP-HPLC）with MeOH-H2O as the mobile phase at 215 nm of the uv-vis wavelength was investigated.A good seperatioin of toosendanin with matrix was obtained within 20 min by using Eclipse XDB-C8 column.The linear regression equation for peak area-toosendain concentration is A=20.818C-31,r=0.9997.

植物性杀虫剂川楝素的开发研究

在研究、开发和使用新型植物性杀虫剂的过程中,以菜青虫为主,对苦楝、川楝树皮中的呋喃三萜类物质——川楝素,从药效、致毒机理、使用技术以及剂型加工工艺等方面做了10多年的研究。这种植物性杀虫物质可破坏菜青虫的中肠组织,并引起一系列生理病变。用楝树皮提取物为主要成份加工配制成0.5％楝素杀虫乳油,取名“蔬果净”,已正式投入生产。该剂安全、高效,使用后无毒害残留,尤适于经济作物上防治有害昆虫,是配合“无污染”蔬菜、果品、茶叶、烟草、中草药等作物生产的良好药剂。

微波辅助提取川楝素的方法研究

利用微波效应,以水为溶剂提取川楝素.研究了微波功率、微波占空比、微波作用时间、溶剂用量等因素对川楝素提取率的影响.确定最佳的提取工艺条件为:微波功率300W,微波作用时间10min,固液比为1∶30,微波占空比50%.提供了一条以水为溶剂、微波为热源提取川楝素的绿色化学途径.

川楝子杀虫成分及其活性探索(Ⅱ)

报道了川楝（ＭｅｌｉａｔｏｏｓｅｎｄａｎＳｉｅｂ．ｅｔＺｕｃｃ．）果实化学成分的初步分离和各组分杀虫活性的研究，通过活性跟踪从氯仿提取物Ｄ部分中分离得到一个未见文献报道的化合物，其结构由波谱和化学性质鉴定为Δ２，３－异川楝素．生测结果表明氯仿提取物Ｂ部分杀蚜虫活性可达９５．１２％，Ｃ部分杀蚜虫（Ａｐｈｉｄ）活性高达１００％，对第４代有抗性的小菜蛾（Ｐｌｕｔｅｌａｘｙｌｏｓｔｅｌａ）显示一定的活性．

川楝子对神经系统的作用及机理探讨

目的:探讨炒黄川楝子乙醇提取物(川楝子提取物)对神经系统的作用机理。方法:采用热板法、辐射热刺激法及电刺激法观察川楝子提取物对小鼠感觉神经的影响,并测算小鼠热痛阈值,A-δ纤维、C纤维的兴奋幅度值,易化幅度值;运用在体间接检测法,考察川楝子提取物对大鼠坐骨神经的神经传导速度(NCV)的影响,通过电镜检测及银染色技术观察川楝子提取物对坐骨神经的病理学改变。结果:川楝子提取物可提高小鼠的热痛阈值及尾痛阈值,延缓大鼠NCV。电镜检查结果表明川楝子提取物可导致大鼠坐骨神经髓鞘纤维脱髓鞘,雪旺氏细胞数目减少。银染色雪旺氏细胞统计结果表明川楝子提取物可显著减少大鼠坐骨神经雪旺氏细胞的数目。结论:川楝子提取物能降低小鼠的痛觉敏感性,延缓大鼠NCV,其机制可能与减少雪旺氏细胞的数目有关。