穿心莲二萜内酯类化合物的合成及抗肿瘤构效关系研究

 目的合成穿心莲二萜内酯类化合物,并进行抗肿瘤活性研究。方法以穿心莲内酯为底物合成14-去氧-11,12-二去氢穿心莲内酯、14-去氧穿心莲内酯、异穿心莲内酯和穿心莲酸等穿心莲二萜内酯类化合物。以人白血病HL-60为体外模型,小鼠H22肝癌皮下移植肿瘤为体内模型观察其抗肿瘤活性,同时观察对小鼠迟发性变态反应及碳粒廓清功能的影响。结果目标物结构经红外、质谱、核磁共振氢谱确证。体外实验,异穿心莲内酯和穿心莲内酯对HL-60细胞的IC₅₀分别为7.15和28.34μmol·L^-1,其余化合物均大于50μmol·L^-1;体内实验,筛选剂量为100mg·kg^-1时,穿心莲内酯和异穿心莲内酯有明显的抗肿瘤活性,抑制率分别为64.4%和61.2%,其余化合物抗肿瘤活性不明显;相同剂量下,穿心莲内酯,穿心莲酸对迟发性变态反应有促进作用,穿心莲内酯,穿心莲酸,14-去氧穿心莲内酯,14-去氧-11,12-二去氢穿心莲内酯能降低小鼠碳粒廓清指数,而异穿心莲内酯对迟发性变态反应和炭粒廓清指数均无影响。结论初步生物活性实验表明,穿心莲二萜内酯类化合物的内酯环是抗肿瘤的必须活性基团;该类化合物的抗肿瘤作用可能与内酯环部分(包括C₁₁和C₁₂)双键的个数及位置和14-位羟基均有一定关系,具有环外12,13-位双键和14-位羟基的抗肿瘤活性较强;异穿心莲内酯的四氢呋喃环有增强抗肿瘤活性之作用。异穿心莲内酯有非常显著的抗肿瘤活性,且对小鼠免疫功能无影响,提示它可能是一类有发展前景的抗肿瘤药物。     

14-脱氧穿心莲内酯和14-脱氧-11,12-二去氢穿心莲内酯对培养的人体内皮细胞NO生成的影响

穿心莲(Andrographis paniculata)是广泛分布于东南亚用于治疗高血压、糖尿病的中药。以前研究表明其所含成分14-脱氧穿心莲内酯(DA)和14-脱氧-11,12-二去氢穿心莲内酯(DDA)对麻醉大鼠有降压作用,对离体大鼠主动脉条有舒张作用,且DDA作用强于DA,其舒血管作用机理可能与激活NO合酶、鸟苷酸环化酶的活性有关。本次探讨了DA和DDA对人体内皮细胞NO生成的刺激作用。     

穿心莲内酯及其衍生物的药理活性研究进展

穿心莲内酯是中药穿心莲的主要有效成分之一。具有解热、抗炎、抗病毒、保肝利胆等作用,临床上主要用于治疗小儿肺炎,上呼吸道感染等疾病。随着对穿心莲内酯药理作用研究的不断深入,其临床应用得到不断拓展[1],并在免疫调节、抗肿瘤、抗糖尿病等方面展示了诱人的应用前景。本文重点综述近年来关于穿心莲内酯的抗炎、免疫调节、抗肿瘤、抗心血管疾病和抗消化系统疾病等机理方面的研究进展。1解热抗炎穿心莲内酯、脱氧穿心莲内酯(DA)、新穿心莲内酯(NA)和脱氧二脱氢穿心莲内酯(DDA)对2,4-二硝基酚或内毒素诱导的发热和蛋清诱导的水肿或巴豆…     

穿心莲内酯及其衍生物药理活性研究

穿心莲内酯为二萜内酯类化合物,由于其具有广泛的药理作用而受到关注。文章简要阐述了穿心莲内酯的理化性质以及提取分离方法。重点综述了穿心莲内酯的药理活性以及穿心莲内酯进行分离纯化和以穿心莲内酯为母体进行不同的取代侧链的结构改造后,生成的穿心莲内酯衍生物或类似物在抗菌、抗炎、心血管系统、免疫调节、抗肿瘤这些方面的药理活性的改善。随着对其药理活性及结构改造的深入研究,穿心莲内酯类新药表现出广阔的研究和开发前景。     

12-亚甲基脲-14-去氧穿心莲内酯衍生物的合成与抗肿瘤活性(英文)

目的:通过对穿心莲内酯引入亲水性基团,探索衍生物的抗肿瘤活性和构效关系。方法:碱性条件下,穿心莲内酯1与硝基甲烷进行Michael加成反应,重排生成12-硝基甲基-14-去氧穿心莲内酯,再以锌粉盐酸还原硝基生成12-氨基亚甲基-14-去氧穿心莲内酯2,最后与异氰酸酯反应成脲3a～3n,所有化合物考察了抗肿瘤和抑制NA活性。结果:经结构改造后,两个化合物(3f和3m)显示了中等的抗肿瘤活性,并且都是单取代芳环,提示芳环的引入优于脂肪链(环)和杂环;所有衍生物都无抑制NA活性。结论:穿心莲内酯对流感病毒神经氨酸酶无抑制活性;12位引入芳环有意义,但芳环所处的支链不能过长;水溶性基团的引入对活性提高没有帮助,具体有待进一步研究。     

穿心莲内酯衍生物的合成研究进展

穿心莲内酯为爵床科植物穿心莲的重要天然活性成分之一,穿心莲内酯及其衍生物具有抗炎、抗病毒、抗肿瘤、抗HIV、保肝活性以及α-葡萄糖苷酶抑制等活性,由于其广泛的药理活性而备受研究者关注。该文对穿心莲内酯衍生物的合成进行综述,并简述其相关的药理活性报道。     

UPLC-Q-TOF-MS筛选穿心莲中亲和Caco-2细胞的活性成分

目的采用超高效液相色谱-四级杆飞行时间质谱(UPLC-Q-TOF-MS)技术筛选穿心莲与Caco-2细胞亲和的活性成分。方法利用Caco-2细胞进行药物摄取结合药物吸收转运实验共同筛选穿心莲的亲和活性成分,采用UPLC-Q-TOF-MS测定亲和前后的细胞样品。根据各化学成分的保留时间、质谱信息,并结合提取离子流图与对照品、相关文献质谱数据对比鉴定各亲和活性成分。结果从穿心莲中共筛选出10种能与Caco-2细胞亲和的活性成分,分别为12,13-双氢穿心莲内酯(1)、黄芩黄酮I-2′-O-葡萄糖苷(2)、穿心莲内酯(3)、14-脱氧-11,12-二脱氢穿心莲内酯苷(4)、7-羟基脱水穿心莲内酯(5)、新穿心莲内酯(6)、3-去氧脱水穿心莲内酯苷(7)、去氧穿心莲内酯(8)和脱水穿心莲内酯(9)和1种未知成分。结论结合UPLC-Q-TOF-MS技术建立的筛选穿心莲中与Caco-2细胞亲和活性成分的方法,可用于筛选中药复杂体系中的活性成分,为进一步研究活性成分群间的协同配伍效应奠定基础。     

穿心莲内酯及其衍生物的药理研究进展

穿心莲内酯是穿心莲的提取物,属于二萜内酯类化合物,是中药穿心莲的主要有效成分之一。本文就主要对穿心莲内酯及其衍生物所具备的清热抗菌、抗炎、抗病毒作用、抗肿瘤、免疫调节及抗心血管疾病等药理学作用进行了阐述,以期为进一步有效利用穿心莲内酯提供参考。     

HPLC-蒸发光散射检测法测定穿心莲制剂中的穿心莲内酯

穿心莲内酯及其相关二萜内酯被认为是穿心莲(Andrographis paniculata)的主要活性成分，具有抗炎、抗过敏、增强免疫、抗病毒、抗氧化、保肝等药理作用，并可应用于心血管疾病。本次采用高效液相色谱-蒸发光散射检测法对穿心莲制剂中的穿心莲内酯进行了分析。     

17-氢-9-去氢穿心莲内酯体外代谢速率及代谢产物研究

应用体外大鼠肝微粒体孵育体系,研究喜炎平注射液中主要有效成分17-氢-9-去氢穿心莲内酯(DHA)的体外代谢速率及代谢产物。将17-氢-9-去氢穿心莲内酯与加入NADPH的大鼠肝微粒体共同孵育,采用超高效液相色谱-三重四极杆串联质谱法(UHPLC-MS/MS)测定其剩余浓度,考察17-氢-9-去氢穿心莲内酯的肝微粒体代谢速率,并采用超高效液相色谱串联飞行时间质谱(UPLC-TOF-MS^E)对孵育体系中17-氢-9-去氢穿心莲内酯的代谢产物进行鉴定。研究结果显示在加入辅酶的大鼠肝微粒体中,17-氢-9-去氢穿心莲内酯代谢速率较快,其半衰期(t_1/2)和肝微粒体中清除率(CL)分别为(19.7±0.5) min和(35.1±0.8) mL·min^-1·g^-1。高分辨质谱数据结合文献信息共鉴定孵育体系中17-氢-9-去氢穿心莲内酯的9个代谢产物,主要为羟基化产物和脱氢产物。鉴定结果为筛选出活性更好的穿心莲二萜内酯类衍生物提供了一定的依据。     

浅谈"心神脑神系统"与肿瘤防治

首先分析了心和脑的关系,说明心主神明与脑主神明构成内在统一的系统,并揭示了该系统的实质;其次阐明了“神经-内分泌-免疫”网络在肿瘤发生与防治中的重要作用;最后从“心神脑神系统”着眼,扩展中医思路,提出防治肿瘤疾病的方法。     

Evaluation of the anti-inflammatory and analgesic properties of individual and combined extracts from Commiphora myrrha, and Boswellia carterii

Aim of the study

The Chinese herbs of myrrh and frankincense are often combined for treating some inflammatory pain diseases with synergistic therapeutic effects. In this study, we investigated the effects of individual herbal extracts and combined extract on anti-inflammatory and analgesic activities in vivo and analyzed the potential bioactive components from the combination extract by ultra-performance liquid chromatography coupled with mass spectrum (UPLC-MS/MS).

Materials and methods

The anti-inflammatory activities were investigated by utilizing the paw edema mice induced by formalin and carrageenan. In addition, we determined the levels of PGE₂ and nitrite in the edema paw. The analgesic activity was examined against oxytocin-induced dysmenorrhea in mice. The effects of the administration of dolantin or indomethacin were also studied for references. The components in combination extract (CWE) were analyzed by UPLC-MS/MS.

Results

The results showed that myrrh water extract (MWE) and the combined extract (CWE) at the 3.9 g/kg, and 5.2 g/kg showed inhibition of formalin-induced paw edema with inhibition rate of 30.44%, and 23.50%, respectively. The PGE₂ production was inhibited significantly by all samples (P < 0.01 or P < 0.05). CWE showed stronger suppression on carrageenan-induced mice paw edema at 2 and 3 h after administration of drugs. The inhibitory effect of CWE on nitrite production was between that of MWE and water extract of frankincense (FWE) at 5.2 g/kg. The dysmenorrhea mice test showed MWE could remarkably reduce the writhing times (P < 0.05) and prolong the latency period, while FWE showed no obvious effects on the writhing times. CWE significantly reduced the writhing times and prolong the latency period (P < 0.01).

Conclusion

These results demonstrated MWE, FWE, and CWE exhibited significant anti-inflammatory and analgesic activities. The findings suggest that CWE may be therapeutically more useful for mitigating inflammatory pain than individual herbal extract. In addition, 12 potential active compounds were identified from CWE. These data may support the fact the traditional application of this combined extract in treating various diseases associated with inflammatory pain.     

大叶山楝萜类化学成分及其生物活性研究进展

大叶山楝Aphanamixis grandifolia为楝科山楝属植物,具有舒筋活络、通痹及祛风除湿等功效。大叶山楝中含有柠檬苦素类衍生物、甘遂烷型三萜、达玛烷型三萜、环阿尔廷烷型三萜、二萜及倍半萜等萜类化合物,具有杀虫、抗肿瘤、抗炎、抗疟疾和抑菌等生物活性。对大叶山楝萜类化学成分及其生物活性研究进展进行综述,以期为该植物的研究和开发利用提供参考。     

宁夏枸杞内生菌的抗菌和抗肿瘤活性研究

为筛选具有抗菌抗肿瘤活性的枸杞内生菌资源,对分离自宁夏枸杞的10株内生菌发酵液的抑菌活性和体外细胞毒活性进行检测,通过ITS和16S rDNA序列分析对菌株进行了分子鉴定。结果表明,5株内生真菌对供试病原菌都未表现出抑制活性,放线菌AL6对3种病原真菌都有一定的抑制作用,而AL5仅对金黄色葡萄球菌有较强抑制活性。但内生真菌的抗肿瘤活性明显强于放线菌。当发酵液浓度为0.2 g·L~(-1)时,有4株内生真菌至少对1种肿瘤细胞的抑制率高于50%。序列分析表明,5株内生真菌隶属于曲霉属、青霉属和翘孢霉属。5株内生放线菌隶属于链霉菌属、微球菌属和拟诺卡氏菌属。曲霉属菌株FL1对A549和HeLa细胞的抑制活性都较强,其IC_(50)分别为0.022,0.028 g·L~(-1),值得进一步研究。     

脑主神明理论的源流及内涵

回顾了先秦、两汉以降有关脑理论的文化背景,以及同时期中医脑主神明理论的发展,剖析脑主神明与心主神明之争的渊源,对中医脑神理论的源流及内涵进行梳理。     

Flavonoid glycosides from the stem bark of Margaritaria discoidea demonstrate antibacterial and free radical scavenging activities

One new flavonoid glycoside, along with three known flavonoid glycosides were isolated from the stem bark of Margaritaria discoidea, which is traditionally used in the management of wounds and skin infections in Ghana. The new flavonoid glycoside was elucidated as hydroxygenkwanin‐8‐C‐[α‐rhamnopyranosyl‐(1 → 6)]‐β‐glucopyranoside (1) on the basis of spectroscopic analysis. The isolated compounds demonstrated free‐radical scavenging as well as some level of antibacterial activities. Microorganisms including Staphylococcus aureus are implicated in inhibiting or delaying wound healing. Therefore, any agent capable of reducing or eliminating the microbial load present in a wound as well as decreasing the levels of reactive oxygen species may facilitate the healing process. These findings therefore provide some support to the ethnopharmacological usage of the plant in the management of wounds. Copyright © 2013 John Wiley & Sons, Ltd.     

Chemical Constituents with Antihyperlipidemic Activities from Desmodium triquetrum

Objective To study the chemical constituents from Desmodium triquetrum and their antihyperlipidemic activities. Methods The constituents of D. triquetrum were isolated and purified using various column chromatographies. Their chemical structures were elucidated using extensive spectroscopic methods. The lipid-lowering effects of the isolates were evaluated in HepG2 cells. Results Nine compounds were obtained from the ethanol extract of D. triquetrum and determined to be 6′-O-cis-p-coumaroyl-3,5-dihydroxyphenyl-β-D-glucopyranoside(1), tadehaginoside(2), rutin(3), quercetin-3-O-β-D-glucopyranoside(4), quercetin-3-O-β-D-galactopyranoside(5), 6-O-(E)-p-hydroxy-cinnamoyl-β-glucose(6), 6-O-(E)-p-hydroxy-cinnamoyl-α-glucose(7), kaempferol-3-O-β-D-rutinoside(8), and 3-O-β-D-galacopyranosyl(6-1)-α-L-rhamnosyl quercetin(9). Compounds 1 and 2 significantly reduced the intracellular content of total cholesterols and triglycerides. Conclusion Compound 1 is a new phenolic compound and exhibits potent anti-hyperlipidemic activity. Additionally, compounds 6 and 7 are isolated from D. triquetrum for the first time.     

木樨草素的药理作用研究进展

木樨草素具有多种药理活性，具体表现在抗肿瘤、抗炎、降血压、抗动脉硬化、抗菌抗病毒以及抗氧化作用等方面。     

真红树林植物化学成分及生物活性研究概况

本文概述了红树林植物的界定标准和中国存在的真红树林种类与分布;并综述了真红树植物的化学成分和生物活性研究情况,在此基础上对其药用前景进行了展望.     

龙胆属植物中的化学成分及药理活性研究进展

结合国内外文献综述了龙胆属植物化学成分的研究进展,并对该属药用植物的药理活性进行了总结.龙胆属植物含有多种化学成分,主要有环烯醚萜及裂环环烯醚萜、(口山)酮、黄酮等;其中环烯醚萜及裂环烯醚萜类成分90多种,(口山)酮类成分100多种,黄酮类成分34种,黄酮类成分主要从该属植物的地上部分得到.该属植物具有显著的保肝、利胆、抗炎、抗病毒等活性.