栀子中环烯醚萜类化合物的研究概况

对栀子中环烯醚萜类化合物的成分及药理研究文献进行了回顾和总结。环烯醚萜类化合物的生物活性范围广,对消化系统、心血管系统、抗肿瘤、抗菌消炎等作用明显,研究前景广阔。参考文献10篇。     

栀子环烯醚萜类化学成分研究

目的 研究栀子Gardenia jasminoides Ellis.的干燥成熟果实中的环烯醚萜类化学成分.方法 采用各种柱色谱方法分离纯化,通过理化常数测定和光谱分析鉴定环烯醚萜类化合物的结构.结果 分离鉴定了9个环烯醚萜类化合物,分别为京尼平苷(1);京尼平-1-O-β-D-龙胆双糖苷(2);genipin-1,10-di-O-β-D-glucopyranoside (3);去乙酰车叶草苷酸甲酯(4);栀子新苷甲酯(5);1-羟基-7-羟甲基-1,4a,5,7a-四氢化环戊二烯骈吡喃-4-醛(6);栀子酸(7);山栀子苷(8);6-O-Methylscandoside Methyl Ester(9).结论 化合物6和9为首次从栀子中分离得到.     

栀子环烯醚萜类成分活性作用的虚拟评价

目的 利用理论对接方法 对栀子中环烯醚萜类成分的可能活性进行虚拟评价.方法 选取6个栀子环烯醚萜类成分,收集现有常见靶标的晶体结构,利用Schrodinger软件进行计算,以分级标准评价选择性.结果 环烯醚萜类的选择性靶标涉及癌症、炎症、肺结核、阿尔茨海默痴、痴呆、糖尿病、哮喘、慢性阻塞性肺疾病、心衰、高血压、自身免疫疾病、抑郁症、疟疾等疾病.糖基对于环烯醚萜类的作用具有重要影响,饱和五元环对于提高选择性具有较人意义.结论 虚拟评价发现的环烯醚萜苷的活性作用与报道的实验结果 吻合较好,表明该技术具有较大的实用性,本研究为利用理论手段研究中药的作用机制进行了有益的尝试.     

天然环烯醚萜类化合物研究进展

环烯醚萜类化合物结构繁多,在自然界中分布广泛,多存在于木犀科、唇形科、茜草科、玄参科等双子叶植物中。近年来对于此类化合物的广泛研究发现其具有多种生物活性,如抗炎、抗肿瘤、治疗糖尿病、保肝、神经系统保护作用及对心血管系统的作用等。此外,环烯醚萜类可作为DNA合成酶抑制剂也有报道。从结构类型、构效关系、生物活性等方面,对环烯醚萜类化合物近年的研究成果进行概述,为基于环烯醚萜类化合物的新药发现和药物设计提供参考。     

梓树落叶中的环烯醚萜类化合物

曾从梓树（Catalpa ovata）果实中分离得到16个环烯醚萜类化合物,本次又从其落叶中分离得到2个新的环烯醚萜类化合物（1、2）和6个人工合成的环烯醚萜类化合物（3～8）,同时,对其主要成分的自由基清除活性进行了研究。     

玄参中环烯醚萜类化合物的研究进展

环烯醚萜类化合物是玄参主要活性成分之一,根据化学结构将其分为环烯醚萜苷和非苷环烯醚萜两大类。并以环烯醚萜苷类化合物的生物合成过程为基础,推测脱羧环烯醚萜苷途径为玄参中环烯醚萜苷类主要生物合成途径。相关研究表明,哈巴苷、哈巴俄苷和桃叶珊瑚苷等成分在抗脑缺血、降血糖、保护心肌细胞等方面发挥重要作用,但仍有大部分环烯醚萜类成分的药理作用并不明晰。通过对玄参中环烯醚萜类化学成分的种类、生物合成技术以及药理作用的相关文献进行综述,为玄参环烯醚萜类化合物的开发应用提供参考。     

裂环烯醚萜类化合物研究进展

综述了1992-2001年新发现的裂环烯醚萜类化合物的结构，并简要总结了其生物活性。     

386 草苁蓉中1个新的环烯醚萜类化合物

曾从草苁蓉（Boschniakia rossica）中分离得到具有滋补作用的肉苁蓉碱和肉苁蓉内酯化合物以及多种环烯醚萜类和苯丙烷类化合物。本次从中分离出1个新的环烯醚萜类化合物（1）、2个已知甾类化合物（2、3）、1个苯丙烷类化合物和甲基P-香豆酯。     

素馨属植物中环烯醚萜类化学成分及生物活性

木樨科素馨属植物在中国民间有广泛的药用基础，其化学成分多样，已分离到挥发油、萜类、黄酮和环烯醚萜类成分。主要介绍了其中的环烯醚萜类成分以及该属植物的抗心律失常、抗炎、解痉等生物活性。     

植物环烯醚萜类化合物生物活性研究进展

环烯醚萜类化合物是一类重要的植物次生代谢产物,具有广泛的生物活性,作者对此类化合物的分布、生物活性进行综述。总结了环烯醚萜类化合物在糖尿病治疗、保肝、抗炎、抗菌、抗肿瘤等方面的应用,为相关药用植物的开发及该类化合物在医药领域上的进一步应用提供参考。     

原小檗碱型生物碱口服给药体内过程研究进展

通过文献检索,整理与分析原小檗碱型生物碱口服给药体内过程的研究进展,以期为其口服剂型选择、药效学与毒理学研究、临床合理用药提供参考资料。检索中国知识资源总库(CNKI)、维普中文科技期刊数据库和西文生物医学期刊文献数据库,对原小檗碱型生物碱类活性成分口服给药后在胃肠道的吸收、体内组织分布、代谢途径与代谢产物、排泄及药动学参数的研究进行文献整理。研究报道涉及多种此类活性成分在肠道的转运机制与转运部位特性、体内组织分布、代谢与排泄特性及主要代谢产物、口服药动学参数等。口服用药的体内过程较为复杂,影响因素众多。现阶段研究尚不够系统、深入,复方配伍用药时在体内各环节可能产生的药物相互作用尚不明确,代谢产物的药理活性还需进一步确认。     

糙苏素的抗肿瘤活性研究

目的:探讨藏药螃蟹甲中环烯醚萜类成分糙苏素(phlomiol)的抗肿瘤作用.方法:采用MTT法检测糙苏素对体外培养的2种人肿瘤细胞增殖的抑制作用;体内试验采用小鼠实体瘤S180、肝癌H22细胞株接种小鼠,连续给药14 d,计算抑瘤率.采用MTT比色法检测糙苏素对S180荷瘤小鼠NK细胞杀伤活性的影响和对S180荷瘤小鼠T淋巴细胞增殖反应的影响.结果:糙苏素在50～150 mg·L-1对2种肿瘤细胞增殖均有抑制作用,且呈剂量依赖关系(r=0.989,P<0.05);体内试验结果显示小鼠分别灌胃给予2.5,5,10 mg·kg-13个剂量的糙苏素,对接种的实体瘤S180、肝癌H22细胞株的抑瘤率分别为28.5%～65.0%.35.0%～74.5%.同时,糙苏素可显著提高S180荷瘤小鼠淋巴细胞增殖活性(P<0.05),显著增加S180荷瘤小鼠NK细胞的杀伤能力(P<0.05).结论:糙苏素对体外培养的人肿瘤细胞和接种的小鼠肿瘤具有明显抑制作用,能够增强淋巴细胞增殖功能和NK细胞的杀伤能力,具有抗肿瘤和免疫调节功能.     

交泰丸有效部位自微乳系统的体内外评价

目的:对交泰丸有效部位自微乳化释药系统质量及大鼠在体肠吸收进行评价。方法:考察交泰丸有效部位自微乳液的外观、自微乳化后微乳粒径分布、外观、形态、类型、自乳化时间、药物含量及自微乳、微乳化后的稳定性;以黄连总碱为指标,运用大鼠在体肠回流模型,分析比较交泰丸有效部位制备自微乳前后对大鼠在体肠吸收的改善。结果:交泰丸有效部位自微乳化后微乳平均粒径为34.12 nm,可在3 min内基本乳化完全;自微乳液在室温下放置3个月较稳定;自微乳化后的微乳液在37℃下0.1 mol.L-1HCl溶液中放置8 h,交泰丸有效部位自微乳液与有效部位溶液剂比较,黄连总碱在体肠灌流液中的相对剩余百分含量(T)和表观吸收速率常数(Ka)值均获得明显提高(P0.01),前者的Ka是后者的152.6%。结论:自微乳化给药系统能显著改善交泰丸有效部位中黄连总碱大鼠小肠吸收,增加肉桂油在制剂中的稳定性。适合难溶性和难吸收药物的口服吸收,提高其生物利用度,是具有良好应用前景的中药制剂新剂型。     

柳氮磺胺吡啶栓剂体内外释药研究

目的:研究柳氮磺胺吡啶栓剂体内外释药规律。方法:于不同时间点采样,测定柳氮磺胺吡啶栓剂溶出度,分析累积释药量;新西兰兔直肠给柳氮磺胺吡啶栓,测定不同时间点血浆中柳氮磺吡啶(SASP)的浓度,应用3P97软件进行药动学分析。结果:SASP栓剂体外释放率较低,家兔体内吸收入血较快,Tpeak0.606 272 h,Cmax2.404 431 mg.L-1。结论:柳氮磺胺吡啶栓剂体内外释药具有较好的相关性。     

In vitro and in vivo anti-inflammatory effect of Rhodomyrtus tomentosa methanol extract

Ethnopharmacological relevance

Rhodomyrtus tomentosa (Aiton) Hassk. is a representative Thai medicinal plant traditionally used in South Asian countries to relieve various inflammatory symptoms. However, no systematic studies on its anti-inflammatory activity and mechanisms have been reported.

Materials and methods

The effect of the methanol extract from the leaves of this plant (Rt-ME) on the production of inflammatory mediators [nitric oxide (NO) and prostaglandin E₂ (PGE₂)] and the molecular mechanism of Rt-ME-mediated inhibition, including target enzymes, were studied with RAW264.7, peritoneal macrophage, and HEK293 cells. Additionally, the in vivo anti-inflammatory activity of this extract was evaluated with mouse gastritis and colitis models.

Results

Rt-ME clearly inhibited the production of NO and PGE₂ in lipopolysaccharide (LPS)-activated RAW264.7 cells and peritoneal macrophages in a dose-dependent manner. According to RT-PCR, immunoblotting and immunoprecipitation analyses and a kinase assay with mRNA, whole cell extract, and nucleus lysates from RAW264.7 cells and mice, it was revealed that Rt-ME was capable of suppressing the activation of both nuclear factor (NF)-κB and activator protein (AP)-1 pathways by directly targeting Syk/Src and IRAK1/IRAK4.

Conclusion

Rt-ME could have anti-inflammatory properties by suppressing Syk/Src/NF-kB and IRAK1/IRAK4/AP-1 pathways and will be further developed as a herbal remedy for preventive and/or curative purposes in various inflammatory diseases.     

LC-MS/MS法研究甘草对雷公藤内酯酮药代动力学及组织分布与排泄的影响

目的:研究甘草对雷公藤内酯酮药代动力学及组织分布与排泄的影响,为阐明甘草对雷公藤的减毒作用机制奠定基础。方法:采用对比试验,将SD大鼠随机分为雷公藤内酯酮单独给药组和雷公藤内酯酮与甘草联合给药组,联合给药组提前灌服甘草后,分别尾静脉注射雷公藤内酯酮1.4mg·kg-1,采用LC-MS/MS法在选择离子监测(SIM)模式下测定雷公藤内酯酮单独给药和与甘草联合给药后不同时间大鼠血浆、组织液和排泄物中的雷公藤内酯酮浓度,比较单独和联合给药后雷公藤内酯酮药代动力学及组织分布与排泄的差异。结果:雷公藤内酯酮在测定范围内均呈良好线性关系(r0.99),日内和日间精密度RSD均小于15%,血浆中提取回收率均大于70%,各组织中提取回收率均大于60%,提取方法稳定可靠;单独给药和与甘草联合给药的药代动力学参数及组织分布与排泄均有明显差异。联合给药组的AUC与t1/2z明显小于单独给药组,而清除率(CL)则增大,说明联合给药组的代谢速度比单独给药组快;在组织分布中,单独给药组和联合给药组中雷公藤内酯酮均主要聚集于肺,联合给药组在组织中的分布浓度比单独给药组低;在排泄中,联合给药组中雷公藤内酯酮的排泄总量大于单独给药组约1倍。结论:甘草对雷公藤内酯酮药代动力学及组织分布与排泄均有显著影响,甘草可加速雷公藤内酯酮体内代谢与排泄,降低组织分布浓度,这可能与甘草降低雷公藤毒性有关。     

In vivo antimalarial activity of Keetia leucantha twigs extracts and in vitro antiplasmodial effect of their constituents

Ethnopharmacological relevance

The West African tree Keetia leucantha (Rubiaceae) is used in traditional medicine in Benin to treat malaria. The twigs dichloromethane extract was previously shown to inhibit in vitro Plasmodium falciparum growth with no cytotoxicity (>100 µg/ml on human normal fibroblasts).

Materials and methods

The dichloromethane and aqueous extracts of twigs of K. leucantha were evaluated in vivo against Plasmodium berghei NK 173 by the 4-day suppressive test and in vitro against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) using the measurement of the plasmodial lactate dehydrogenase activity. Bioguided fractionations were realized and compounds were structurally elucidated using extensive spectroscopic analysis.

Results

The in vivo antimalarial activity of K. leucantha dichloromethane and aqueous twigs extracts were assessed in mice at the dose of 200 mg/kg/day. Both extracts exhibited significant effect in inhibiting parasite growth by 56.8% and 53.0% (p<0.0001) on day 7-postinfection. An LC–MS analysis and bioguided fractionations on the twigs dichloromethane extract led to the isolation and structural determination of scopoletin (1), stigmasterol (2), three phenolic compounds: vanillin (3), hydroxybenzaldehyde (4) and ferulaldehyde (5), eight triterpenic esters (6–13), oleanolic acid and ursolic acid. The antiplasmodial activity of the mixture of the eight triterpenic esters showed an antiplasmodial activity of 1.66±0.54 µg/ml on the 3D7 strain, and the same range of activity was observed for isolated isomers mixtures.

Conclusions

This is the first report on the in vivo activity of K. leucantha extracts, the isolation of thirteen compounds and analysis of their antiplasmodial activity. The results obtained may partially justify the traditional use of K. leucantha to treat malaria in Benin.     

Inhibitory effect of Thymus caramanicus Jalas on hyperglycemia-induced apoptosis in in vitro and in vivo models of diabetic neuropathic pain

Ethnopharmacological relevance

Since Thymus caramanicus Jalas is used as a folk medicine for the treatment of rheumatism, skin disorders, bacterial infections and diabetes and it contain antioxidant agents, we decided to investigate the possible effects of Thymus caramanicus Jalas (TCJ) extract on in vitro and in vivo models of diabetic neuropathy.

Materials and methods

The high glucose-induced cell injury in Pheochromocytoma (PC12) cells and streptozotocin-induced diabetic rats were used. Tail-flick and rotarod treadmill assessments were used to determine nociceptive threshold and motor coordination. Cell viability was determined by MTT assay test. Western blotting was performed to measurement of apoptosis markers.

Results

The data showed that elevation of glucose consecutively increases functional cell injury and apoptosis. Furthermore, diabetic rats developed thermal hyperalgesia and motor deficit. Activated caspase 3, cytochrome c release and Bax/Bcl-2 ratio were significantly increased in high glucose-treated PC12 cells and in spinal cord of diabetic animals. TCJ extract (60 and 80 µg/ml) attenuates high glucose-induced PC12 cells damage and apoptosis. In diabetic animals, TCJ extract at daily doses of 100 and 150 mg/kg ameliorated hyperalgesia and suppressed spinal apoptosis.

Conclusion

The data indicate that TCJ extract has neuroprotective effects against high glucose-induced neural damage. These protective effects are mediated, at least in part, through attenuation of neural apoptosis and suggest therapeutic potential of TCJ extract in amelioration of diabetic neuropathy.