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991.
目的 建立同时测定Caco-2细胞模型中苦参碱、氧化槐果碱和氧化苦参碱的HPLC方法,探讨苦参总生物碱在Caco-2细胞模型的吸收机制.方法 利用人源结肠腺癌细胞系Caco-2细胞单层模型,研究苦参碱、氧化槐果碱和氧化苦参碱由细胞绒毛膜面供给侧(AP)→基底外侧(BL)和BL→AP侧两个方向的转运过程;HPLC-UV法测定上述3个生物碱的量;计算转运参数和表观渗透系数(Papp).结果 苦参总碱给药后,苦参碱、氧化槐果碱和氧化苦参碱由AP→BL侧的Papp分别为(1.098±0.092)×10-5、(1.434±0.098)×10-5、(3.87±0.64)×10-6cm/s,由BL→AP侧的Papp分别为(1.104±0.098)×10-5、(1.034±0.079)×10-5、(2.75±0.33)×10-6 cm/s,与文献报道的单体化合物给药相比,氧化槐果碱和氧化苦参碱双向转运的Papp明显增大.苦参碱、氧化槐果碱和氧化苦参碱的表观渗透率值分别为1.01、0.72、0.71.结论 苦参总生物碱中苦参碱、氧化槐果碱和氧化苦参碱仍主要以被动吸收方式进入体内,但比各单体给药吸收更好. 相似文献
992.
目的 观察附子总生物碱对二甲基苯葸诱导的乳腺癌小鼠体征、部分血液学指标及肿瘤的影响.方法 小鼠分为对照组、模型组、附子总生物碱组.模型组小鼠每天sc二甲基苯蒽橄榄油溶液50 mg/kg,每周2次、连续5周,建立乳腺癌模型,给药组在每天给予二甲基苯蒽的同时,给予附子总生物碱2 mg/kg,观察实验期间各组小鼠乳腺肿瘤的潜伏期、发生率、外观、体温和外耳微循环变化,检测血清中雌二醇和孕酮水平、红细胞Na+,K+-ATP酶和Ca2+,Mg2+-ATP酶活性及血液流变学指标,综合评价附子总生物碱对小鼠乳腺癌的影响.结果 模型组小鼠随给药时间的延长逐渐出现畏寒喜暖、蜷缩少动、体温下降、外耳微循环受阻状况,同时血中雌二醇和孕酮水平升高,红细胞ATP酶活性降低,全血黏度及红细胞聚集指数增高;附子总生物碱可以显著改善上述指标变化,阻止肿瘤生长.结论 二甲基苯葸诱导的乳腺癌小鼠表现为体寒血瘀体征,附子总生物碱能改善这些症状,阻止肿瘤进展. 相似文献
993.
Soultati A Mountzios G Avgerinou C Papaxoinis G Pectasides D Dimopoulos MA Papadimitriou C 《Cancer treatment reviews》2012,38(5):473-483
In cancer biology angiogenesis plays a vital role in tumour growth and its subsequent metastatic potential. By targeting the angiogenic process, a new treatment strategy was added in the clinician's therapeutic armamentarium. On the other hand, numerous classic cytotoxic agents are currently considered as potential angiogenesis inhibitors, although they were not originally developed as such, representing the so-called "accidental" anti-angiogenic drugs. The discovery of these new properties of classic cytotoxic agents led to the re-evaluation of their effect on vascular cells, rendering thus the endothelium an appealing target for therapeutic intervention, either with chemotherapy alone or with combination of cytotoxics with molecular angiogenesis inhibitors. Moreover, current evidence supports that chemotherapy-induced endothelial dysfunction constitutes an integrating predictive marker of future cardiovascular events and correlates well with traditional cardiovascular risk factors. It has therefore been suggested that evaluation of endothelial function may be useful in identifying asymptomatic subjects at high risk for cardiovascular events as well as for risk stratification of patients with established cardiovascular disease. Integration of the assessment of endothelial function in the clinical setting will thus enable effective intervention strategies to prevent or minimize the impact of these late adverse effects and design accurate follow-up protocols focused on cardiovascular complications. In the current review we provide a comprehensive overview of the effects of cytotoxic chemotherapeutic agents on endothelial function and the clinical implications of chemotherapy-associated endothelial toxicity in patients with cancer. 相似文献
994.
Chia-Chi Wang Qingsu Xia Meng Li Shuguang Wang Yuewei Zhao William H. Tolleson 《journal of environmental science and health part c-environmental carcinogenesis & ecotoxicology reviews》2014,32(4):362-384
Pyrrolizidine alkaloids, produced by a large number of poisonous plants with wide global distribution, are associated with genotoxicity, tumorigenicity, and hepatotoxicity in animals and humans. Mammalian metabolism converts pyrrolizidine alkaloids to reactive pyrrolic metabolites (dehydropyrrolizidine alkaloids) that form covalent protein and DNA adducts. Although a mechanistic understanding is currently unclear, pyrrolizidine alkaloids can cause secondary (hepatogenous) photosensitization and induce skin cancer. In this study, the phototoxicity of monocrotaline, riddelliine, dehydromonocrotaline, dehydroriddelliine, and dehydroretronecine (DHR) in human HaCaT keratinocytes under ultraviolet A (UVA) irradiation was determined. UVA irradiation of HaCaT cells treated with dehydromonocrotaline, dehydroriddelline, and DHR resulted in increased release of lactate dehydrogenase and enhanced photocytotoxicity proportional to the UVA doses. UVA-induced photochemical DNA damage also increased proportionally with dehydromonocrotaline and dehydroriddelline. UVA treatment potentiated the formation of 8-hydroxy-2′-deoxyguanosine DNA adducts induced by dehydromonocrotaline in HaCaT skin keratinocytes. Using electron spin resistance trapping, we found that UVA irradiation of dehydromonocrotaline and dehydroriddelliine generates reactive oxygen species (ROS), including hydroxyl radical, singlet oxygen, and superoxide, and electron transfer reactions, indicating that cytotoxicity and genotoxicity of these compounds could be mediated by ROS. Our results suggest that dehydropyrrolizidine alkaloids formed or delivered to the skin cause pyrrolizidine alkaloid-induced secondary photosensitization and possible skin cancer. 相似文献
995.
996.
S.G. Abdel-Moty S Sakai N Aimi H Takayama M Kitajima A El-Shorbagi A.N. Ahmed N.M. Omar 《European journal of medicinal chemistry》1998,32(12):1009-1017
dl-1-(1-Oxo-3,4-threo-3,4,5-trihydroxy-1-pentyl)-β-carboline 16a was synthesized from 1-formyl-β-carboline in 13 steps. The prepared compound is one of the diastereomers of an alkaloid 3 produced by the inter-generic somatic hybrid cell culture of Rauwolfia serpentina Benth and Rhazya stricta Decaisne (family: Apocynaceae). The N9-benzyl and N9-methyl derivatives 16b,c were also prepared. The final compounds and some of the intermediates showed cytotoxic activity against human promyelocytic leukemia cells HL 60 and/or human diploid embryonic lung fibroblast cells. 相似文献
997.
目的 研究草问荆总生物碱(TAEP)对小鼠脑单胺氧化酶—B(MAO—B)活性的影响,揭示TAEP对中枢神经系统抑制作用的机制。方法 采用紫外分光光度法测定MAO—B的活性。结果 TAEP对小鼠脑MAO—B具有明显的激活作用,并具有对抗烟肼酰胺抑制小鼠脑MAO—B活性的作用。结论 TAEP是MAO—B的激动药,有单胺代谢作用,这可能是TAEP中枢抑制作用的作用机制之一。 相似文献
998.
从中药吴茱萸(Evodia rutaecarpa [juss] Benth)中分离出9个吲哚类生物碱和1个芳香胺,经光谱分析鉴定其结果为:evodiamine(1),rutaecarpine(2),formyldihydrorutaecarpine(3),goshuyuamide-I(4),evodiamide(5 ),hy挹minβ-carboline(7),1,2,3,4,-tetrahydro-1-oxo-β-carbolie(8),dehydroevodiamine(9)的N-methylanthranylamide(10),其中9是新的天然产物,7是首次从该属植物中分离得到。 相似文献
999.
1000.