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Reversal of tamoxifen resistance by artemisinin in ER+breast cancer:bioinformatics analysis and experimental validation 被引量:1
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作者 ZHILI ZHUO DONGNI ZHANG +4 位作者 WENPING LU XIAOQING WU YONGJIA CUI WEIXUAN ZHANG MENGFAN ZHANG 《Oncology Research》 SCIE 2024年第6期1093-1107,共15页
Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug re... Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer. 展开更多
关键词 ARTEMISININ Tamoxifen resistance Breast cancer
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通过鉴定关键靶标蛋白探究青蒿素抗疟机制
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作者 Peng Gao Jianyou Wang +8 位作者 Jiayun Chen Liwei Gu Chen Wang Liting Xu Yin Kwan Wong Huimin Zhang Chengchao Xu Lingyun Dai Jigang Wang 《Engineering》 SCIE EI CAS CSCD 2023年第12期86-97,共12页
The widespread use of artemisinin(ART)and its derivatives has significantly reduced the global burden of malaria;however,malaria still poses a serious threat to global health.Although significant progress has been ach... The widespread use of artemisinin(ART)and its derivatives has significantly reduced the global burden of malaria;however,malaria still poses a serious threat to global health.Although significant progress has been achieved in elucidating the antimalarial mechanisms of ART,the most crucial target proteins and pathways of ART remain unknown.Knowledge on the exact antimalarial mechanisms of ART is urgently needed,as signs of emerging ART resistance have been observed in some regions of the world.Here,we used a combined strategy involving mass spectrometry-coupled cellular thermal shift assay(MS-CETSA)and transcriptomics profiling to identify a group of putative antimalarial targets of ART.We then conducted a series of validation experiments on five prospective protein targets,demonstrating that ART may function against malaria parasites by interfering with redox homeostasis,lipid metabolism,and protein synthesis processes.Taken together,this study provides fresh perspectives on the antimalarial mechanisms of ART and identifies several crucial proteins involved in parasite survival that can be targeted to combat malaria. 展开更多
关键词 ARTEMISININ ANTIMALARIA Target identification MS-CETSA TRANSCRIPTOMICS
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Designing Artemisinins with Antimalarial Potential, Combining Molecular Electrostatic Potential, Ligand-Heme Interaction and Multivariate Models
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作者 Josué de Jesus Oliveira Araújo Ricardo Morais de Miranda +10 位作者 Jeferson Stiver Oliveira de Castro Antonio Florêncio de Figueiredo Ana Cecília Barbosa Pinheiro Sílvia Simone dos Santos Morais Marcos Antonio Barros dos Santos Andréia de Lourdes Ribeiro Pinheiro Andréia de Lourdes Ribeiro Pinheiro Fábio dos Santos Gil Heriberto Rodrigues Bitencourt Gustavo Nery Ramos Alves José Ciríaco Pinheiro 《Computational Chemistry》 CAS 2023年第1期1-23,共23页
Artemisinins tested against W-2 strains of malaria falciparum are investigated with molecular electrostatic potential (MEP), in an attempt to identify key features of the compounds that are necessary for their activit... Artemisinins tested against W-2 strains of malaria falciparum are investigated with molecular electrostatic potential (MEP), in an attempt to identify key features of the compounds that are necessary for their activities, as well as to investigate likely interactions with the receptor in a biological process and to use that information to propose new molecules. In order to discover the best geometry involving the ligand-receptor complexes (heme) studied and help in the proposition of the new derivatives, molecular simulations of interactions between the most negative charged region around the peroxide and heme locates (the ones around the Fe2+ ion) were carried out. In addition, PCA (principal components analysis), HCA (hierarchical cluster analysis), SDA (stepwise discriminant analysis), and KNN (K-nearest neighbor) multivariate models were employed to investigate which descriptors are responsible for the classification between the higher and lower antimalarial activity of the compounds, and also this information was used to propose new potentially active molecules. The information accumulated in studies of MEP, molecular docking, and multivariate analysis supported the proposal of new structures with potential antimalarial activities. The multivariate models constructed were applied to the new structures and indicated numbers 19 and 20 as the most prominent for syntheses and biological assays. 展开更多
关键词 ARTEMISININS Antimalarial Potential Molecular Electrostatic Potential Ligand-Heme Interaction Multivariate Models
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Pharmacognostic and phytochemical studies as an invaluable approach for correct identification of medicinal plants:The case of Artemisia vulgaris L.substituted for Artemisia annua L.in Western Uganda
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作者 Ivan Kahwa Clement Olusoji Ajayi +12 位作者 Reenu Yadav Nagendra Singh Chauhan Kamal Shah Abdelgadir Alamin Abdelgadir Efrata Ashuro Shegena Salome Daniel Timothy Omara John Baptist Asiimwe Hilda Ikiriza Shabnoor Iqbal Casim Umba Tolo Anke Weisheit Patrick Engeu Ogwang 《TMR Integrative Medicine》 2023年第4期1-13,共13页
Background:Different parts of Artemisia vulgaris L.(A.vulgaris)are ethno-medicinally used as an emmenagogue and for the treatment of ailments such as malaria fever,ulcers,and cancer.However,anecdotal evidence shows th... Background:Different parts of Artemisia vulgaris L.(A.vulgaris)are ethno-medicinally used as an emmenagogue and for the treatment of ailments such as malaria fever,ulcers,and cancer.However,anecdotal evidence shows that the plant is often substituted for Artemisia annua L.(A.annua)by herbalists in Western Uganda due to similarities in their morphology.Misidentification of medicinal plants and mislabelling of herbal products have been incriminated in toxicity and adverse health outcomes in traditional medicine practise.Because safety continues to be a major issue with the use of herbal remedies,it becomes imperative therefore that medicinal plants should be correctly identified.Methods:This study focused on investigating the macroscopic,microscopic,physicochemical characteristics and phytochemical composition of A.vulgaris leaves compared to A.annua to ease its correct identification.Results:The results showed that there are some colour differences between the leaves of the two species,with a close arrangement of microscopic features but different leaf constants.The leaves of the two Artemisia species had similar tastes,but their shapes and colours(greenish-yellow for A.annua and dark green for A.vulgaris)can be used by the local community to distinguish between them.The artemisinin content was higher in A.vulgaris leaves(1.72%)than in A.annua(1.43%),but the reverse was observed for the total flavonoid content.Conclusion:This observation could justify the change in the use of A.vulgaris by the indigenous community in western Uganda.Further studies should consider the pharmacognostic comparison of A.annua with other species in the genus Artemisia and the use of molecular techniques such as DNA barcoding. 展开更多
关键词 ARTEMISININ traditional medicine MISIDENTIFICATION microscopic studies
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Effects of Fungal Elicitors on Cell Growth and Artemisinin Accumulation in Hairy Root Cultures of Artemisia annua 被引量:13
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作者 王红 叶和春 +2 位作者 李国凤 刘本叶 种康 《Acta Botanica Sinica》 CSCD 2000年第9期905-909,共5页
The artemisinin accumulation in the hairy root cultures of Artemisia annua L. was enhanced via a treatment of three fungal elicitors separately ( Verticillium dahliae Kleb., Rhizopus stolonifer (Ehrenb. ex ... The artemisinin accumulation in the hairy root cultures of Artemisia annua L. was enhanced via a treatment of three fungal elicitors separately ( Verticillium dahliae Kleb., Rhizopus stolonifer (Ehrenb. ex Fr.) Vuill and Colletotrichum dematium (Pers.) Grove). Among these three elicitors, V. dahliae had the highest inducing efficiency, but none of them manifests any noticeable effects on the cell growth of the hairy root cultures. The artemisinin content of the hairy root cultures treated with V. dahliae elicitor was 1.12 mg/g DW, which was 45% higher than the control (0.77 mg/g DW). The results showed that elicitation was dependent on the elicitor concentration, the incubation period and the physiological stage at which the hairy root cultures were treated. In addition, the authors found that for V. dahliae , the optimum concentration was 0.4 mg carbohydrate per millilitre medium, the strongest response of A. annua hairy root cultures to the elicitation was at the late exponential growth stage, and the highest artemisinin content of the hairy root cultures was on the 4th day post treatment. 展开更多
关键词 Artemisia annua hairy root cultures ARTEMISININ fungal elicitor
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Elicitation on Artemisinin Biosynthesis in Artemisia annua Hairy Roots by the Oligosaccharide Extract from the Endophytic Colletotrichum sp. B501 被引量:12
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作者 王剑文 夏仲豪 谭仁祥 《Acta Botanica Sinica》 CSCD 2002年第10期1233-1238,共6页
The oligosaccharide elicitor from the mycelial wall of an endophytic Colletotrichum sp. B501 promoted the production of artemisinin in Artemisia annua L. hairy root culture. When hairy roots of 22-day-old cultures (la... The oligosaccharide elicitor from the mycelial wall of an endophytic Colletotrichum sp. B501 promoted the production of artemisinin in Artemisia annua L. hairy root culture. When hairy roots of 22-day-old cultures (later growth phase) were exposed to the elicitor (20 mg/L) for 4 d, the maximum content of artemisinin reached 1.15 mg/g, a 64.29% increment over the control. The electron X-ray microanalysis disclosed the rapid accumulation of Ca 2+ in the elicited cortical cells of hairy root. The electronic microscope observation revealed the high electron density area in vacuole of elicited cells. During the first day of elicitation the peroxidase activity of hairy roots was improved sharply. Some cellular morphological changes including cell shrinkage, condensation of cytoplasm and nuclear fragmentation, coincident with the appearance of DNA ladders, were observed after the third day of elicitation. It was suggested that the oligosaccharide elicitor triggered the programmed cell death, which may provide the substance or chemical signal for artemisinin biosynthesis. 展开更多
关键词 Artemisia annua Colletotrichum sp. B501 a fungal endophyte oligosaccharide elicitor ARTEMISININ eliciting response
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青蒿素之母——2015年诺贝尔生理学或医学奖新科得主屠呦呦(二) 被引量:11
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作者 朱安远 郭华珍 《中国市场》 2016年第14期186-194,共9页
2015年10月5日,中国中医科学院(原中国中医研究院)终身研究员兼首席研究员、女药学家、药物化学家、医学家和教育家屠呦呦以创制新型抗疟药物——青蒿素及其首个衍生物双氢青蒿素而赢得当年诺贝尔生理学或医学奖之殊荣,特大喜讯传来,国... 2015年10月5日,中国中医科学院(原中国中医研究院)终身研究员兼首席研究员、女药学家、药物化学家、医学家和教育家屠呦呦以创制新型抗疟药物——青蒿素及其首个衍生物双氢青蒿素而赢得当年诺贝尔生理学或医学奖之殊荣,特大喜讯传来,国内舆论媒体亢奋,国人无不欢欣鼓舞。屠呦呦先生是首位荣获诺贝尔科学奖的中国大陆本土科学家、首位华裔女性诺奖得主和诺医奖得主,这是中国医学界尤其是中医学界的重大历史性突破,这一荣耀将永远铭记在中国科技发展史上。详细介绍了屠呦呦女士的生平、主要学术成就与贡献、与疟疾直接相关的诺医奖以及青蒿素类抗疟药物获得的各种国内外奖项,简明扼要地阐述了青蒿素类抗疟药物的发现(发明)简史,不惜浓墨重彩全方位地展示了以屠呦呦为杰出代表的中国科学家群英谱的奋斗历程和辉煌成就。 展开更多
关键词 屠呦呦 寄生虫病 疟疾(malaria) 疟原虫 抗疟药物(antimalarial drug) 剂型 抗药性(耐药性) 中药 西药(化学药品) 青蒿 黄花蒿 青蒿素(artemisinin) 衍生物(derivative) 双氢青蒿素DHA(dihydroartemisinin) 蒿甲醚(artemether) 蒿乙醚(artemotil/arteether) 青蒿琥酯(artesunate) 卡罗琳医学院诺贝尔大会 生理学或医学奖诺贝尔委员会(医诺委) 诺贝尔生理学或医学奖(诺医奖)
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Selective Effect of Qinghaosu on Different Stages of Plasmodium falciparum in Vitro 被引量:1
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作者 叶祖光 CarolynDoak KnoxVanDyke 《Journal of Chinese Pharmaceutical Sciences》 CAS 1993年第1期64-68,共5页
Using highly synchronous cultures of Plasmodium falciparum in vitro,the susceptibi- lity of the different stages of the intraerythrocytic parasites to Qinghaosu (QHS) was assessed.The anti- parasitic effect of QHS was... Using highly synchronous cultures of Plasmodium falciparum in vitro,the susceptibi- lity of the different stages of the intraerythrocytic parasites to Qinghaosu (QHS) was assessed.The anti- parasitic effect of QHS was measured by comparing the changes of irradiation of^3 H-hypoxanthine in- corporated into the nucleic acids of parasites exposed to various concentrations of QHS at different stages of growth.It was found that the trophozoite stage of the parasite was the most sensitive to QHS, whereas the early ring stage was the least sensitive,and the sensitivities of the late ring and schizont stages fell between those of the early ring and trophozoite stages.The results revealed the correlation of stage-dependent effects of QHS with the blockade of the protein metabolism of the parasite. 展开更多
关键词 Qinghaosu(artemisinin) Antimalarial drug Plasmodium falciparum MALARIA
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青蒿素之母——2015年诺贝尔生理学或医学奖新科得主屠呦呦(三) 被引量:8
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作者 朱安远 郭华珍 《中国市场》 2016年第18期233-245,共13页
2015年10月5日,中国中医科学院(原中国中医研究院)终身研究员兼首席研究员、女药学家、药物化学家、医学家和教育家屠呦呦以创制新型抗疟药物——青蒿素及其首个衍生物双氢青蒿素而赢得当年诺贝尔生理学或医学奖之殊荣,特大喜讯传来,国... 2015年10月5日,中国中医科学院(原中国中医研究院)终身研究员兼首席研究员、女药学家、药物化学家、医学家和教育家屠呦呦以创制新型抗疟药物——青蒿素及其首个衍生物双氢青蒿素而赢得当年诺贝尔生理学或医学奖之殊荣,特大喜讯传来,国内舆论媒体亢奋,国人无不欢欣鼓舞。屠呦呦先生是首位荣获诺贝尔科学奖的中国大陆本土科学家、首位华裔女性诺奖得主和诺医奖得主,这是中国医学界尤其是中医学界的重大历史性突破,这一荣耀将永远铭记在中国科技发展史上。详细介绍了屠呦呦女士的生平、主要学术成就与贡献、与疟疾直接相关的诺医奖以及青蒿素类抗疟药物获得的各种国内外奖项,简明扼要地阐述了青蒿素类抗疟药物的发现(发明)简史,不惜浓墨重彩全方位地展示了以屠呦呦为杰出代表的中国科学家群英谱的奋斗历程和辉煌成就。 展开更多
关键词 屠呦呦 寄生虫病 疟疾(malaria) 疟原虫 抗疟药物(antimalarial drug) 剂型 抗药性(耐药性) 中药 西药(化学药品) 青蒿 黄花蒿 青蒿素(artemisinin) 衍生物(derivative) 双氢青蒿素DHA(dihydroartemisinin) 蒿甲醚(artemether) 蒿乙醚(artemotil/arteether) 青蒿琥酯(artesunate) 卡罗琳医学院诺贝尔大会 生理学或医学奖诺贝尔委员会(医诺委) 诺贝尔生理学或医学奖(诺医奖)
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青蒿素之母——2015年诺贝尔生理学或医学奖新科得主屠呦呦(一) 被引量:10
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作者 朱安远 郭华珍 《中国市场》 2016年第9期199-208,共10页
2015年10月5日,中国中医科学院(原中国中医研究院)终身研究员兼首席研究员、女药学家、药物化学家、医学家和教育家屠呦呦以创制新型抗疟药物——青蒿素及其首个衍生物双氢青蒿素而赢得当年诺贝尔生理学或医学奖之殊荣,特大喜讯传来,国... 2015年10月5日,中国中医科学院(原中国中医研究院)终身研究员兼首席研究员、女药学家、药物化学家、医学家和教育家屠呦呦以创制新型抗疟药物——青蒿素及其首个衍生物双氢青蒿素而赢得当年诺贝尔生理学或医学奖之殊荣,特大喜讯传来,国内舆论媒体亢奋,国人无不欢欣鼓舞。屠呦呦先生是首位荣获诺贝尔科学奖的中国大陆本土科学家、首位华裔女性诺奖得主和诺医奖得主,这是中国医学界尤其是中医学界的重大历史性突破,这一荣耀将永远铭记在中国科技发展史上。详细介绍了屠呦呦女士的生平、主要学术成就与贡献、与疟疾直接相关的诺医奖以及青蒿素类抗疟药物获得的各种国内外奖项,简明扼要地阐述了青蒿素类抗疟药物的发现(发明)简史,不惜浓墨重彩全方位地展示了以屠呦呦为杰出代表的中国科学家群英谱的奋斗历程和辉煌成就。 展开更多
关键词 屠呦呦 寄生虫病 疟疾(malaria) 疟原虫 抗疟药物(antimalarial drug) 剂型 抗药性(耐药性) 中药 西药(化学药品) 青蒿 黄花蒿 青蒿素(artemisinin) 衍生物(derivative) 双氢青蒿素DHA(dihydroartemisinin) 蒿甲醚(artemether) 蒿乙醚(artemotil/arteether) 青蒿琥酯(artesunate) 卡罗琳医学院诺贝尔大会 生理学或医学奖诺贝尔委员会(医诺委) 诺贝尔生理学或医学奖(诺医奖)
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青蒿素之母——2015年诺贝尔生理学或医学奖新科得主屠呦呦(四) 被引量:9
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作者 朱安远 郭华珍 《中国市场》 2016年第22期260-272,共13页
2015年10月5日,中国中医科学院(原中国中医研究院)终身研究员兼首席研究员、女药学家、药物化学家、医学家和教育家屠呦呦以创制新型抗疟药物——青蒿素及其首个衍生物双氢青蒿素而赢得当年诺贝尔生理学或医学奖之殊荣,特大喜讯传来,国... 2015年10月5日,中国中医科学院(原中国中医研究院)终身研究员兼首席研究员、女药学家、药物化学家、医学家和教育家屠呦呦以创制新型抗疟药物——青蒿素及其首个衍生物双氢青蒿素而赢得当年诺贝尔生理学或医学奖之殊荣,特大喜讯传来,国内舆论媒体亢奋,国人无不欢欣鼓舞。屠呦呦先生是首位荣获诺贝尔科学奖的中国大陆本土科学家、首位华裔女性诺奖得主和诺医奖得主,这是中国医学界尤其是中医学界的重大历史性突破,这一荣耀将永远铭记在中国科技发展史上。详细介绍了屠呦呦女士的生平、主要学术成就与贡献、与疟疾直接相关的诺医奖以及青蒿素类抗疟药物获得的各种国内外奖项,简明扼要地阐述了青蒿素类抗疟药物的发现(发明)简史,不惜浓墨重彩全方位地展示了以屠呦呦为杰出代表的中国科学家群英谱的奋斗历程和辉煌成就。 展开更多
关键词 屠呦呦 寄生虫病 疟疾(malaria) 疟原虫 抗疟药物(antimalarial drug) 剂型 抗药性(耐药性) 中药 西药(化学药品) 青蒿 黄花蒿 青蒿素(artemisinin) 衍生物(derivative) 双氢青蒿素DHA(dihydroartemisinin) 蒿甲醚(artemether) 蒿乙醚(artemotil/arteether) 青蒿琥酯(artesunate) 卡罗琳医学院诺贝尔大会 生理学或医学奖诺贝尔委员会(医诺委) 诺贝尔生理学或医学奖(诺医奖)
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Effects of Ag-carrying Zirconium Phosphate on the Kinetics of Growth of the Roots of Culture Artemisia annua
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作者 欧阳杰 王晓东 +1 位作者 赵兵 王玉春 《Acta Botanica Sinica》 CSCD 2003年第2期136-139,共4页
在植物组织和细胞培养过程中 ,尤其是在生物反应器培养中的染菌问题 ,一直是制约植物细胞培养工业化的难题。通过比较各种防腐剂的抑菌效果 ,确定银型磷酸锆盐抗菌粉为青蒿根培养的最佳防腐剂。银型磷酸锆盐抗菌粉在浓度为 30mg/L时 ,... 在植物组织和细胞培养过程中 ,尤其是在生物反应器培养中的染菌问题 ,一直是制约植物细胞培养工业化的难题。通过比较各种防腐剂的抑菌效果 ,确定银型磷酸锆盐抗菌粉为青蒿根培养的最佳防腐剂。银型磷酸锆盐抗菌粉在浓度为 30mg/L时 ,既能降低培养液的染菌几率 ,又不明显抑制青蒿根的生长及青蒿素的生物合成。在添加 30mg/L抗菌粉的培养液中进行的青蒿根生长、pH值变化以及残糖、铵离子和硝酸根离子消耗的动力学研究表明 ,在 4 0d内青蒿根在培养液中生长良好 ,营养成分的消耗和对照呈相似的趋势。 展开更多
关键词 Artemisia annua hairy roots ARTEMISININ Ag-carrying zirconium phosphate (ACZP) KINETICS
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Biotransformation of Artemisinin by Hairy Root Cultures of Rheum palmatum L. 被引量:3
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作者 李莉欣 苏艳芳 +1 位作者 刘晓峰 果德安 《Journal of Chinese Pharmaceutical Sciences》 CAS 2002年第4期122-124,共3页
The biotransformation of artemisinin by hairy root cultures ofRheum palmatum L. was investigated for the first time. The main product, deoxyartemisinin, was isolated and characterized on the basis of its spectral data.
关键词 ARTEMISININ Deoxyartemisinin Rheum palmatum hairy root cultures BIOTRANSFORMATION
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Research Progresses on Extraction and Detection Techniques of Artemisinin 被引量:2
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作者 廖巧 龙世平 杨春贤 《Agricultural Science & Technology》 CAS 2012年第8期1631-1636,共6页
[Objective] The aim was to make a summary on research progresses on extraction and detection techniques of artemisinin. [Method] In the research, the concerning progress was made based on physicochemical property, sou... [Objective] The aim was to make a summary on research progresses on extraction and detection techniques of artemisinin. [Method] In the research, the concerning progress was made based on physicochemical property, source, extraction methods and detection technology of artemisinin. [Result] Artemisinin is colorless acicular crystal and easier to be dissolved in organic solvent. The extraction methods of artemisinin include organic solvent extraction, ultrasonic extraction, microwave extraction and supercritical fluid extraction; the detection technologies include ultraviolet spectrophotometry, high performance liquid chromatography and HPLC-evaporative light-scattering. [Conclusion] The research laid foundation for further exploration and global market. 展开更多
关键词 ARTEMISININ EXTRACTION Content detection
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Artemisinin, the Magic Drug Discovered from Traditional Chinese Medicine 被引量:24
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作者 Jigang Wang Chengchao Xu +4 位作者 Yin Kwan Wong Yujie Li Fulong Liao Tingliang Jiang Youyou Tu 《Engineering》 SCIE EI 2019年第1期32-39,共8页
Artemisinin and its derivatives represent the most important and influential class of drugs in the fight against malaria. Since the discovery of artemisinin in the early 1970s, the global community has made great stri... Artemisinin and its derivatives represent the most important and influential class of drugs in the fight against malaria. Since the discovery of artemisinin in the early 1970s, the global community has made great strides in characterizing and understanding this remarkable phytochemical and its unique chemical and pharmacological properties. Today, even as artemisinin continues to serve as the foundation for antimalarial therapy, numerous challenges have surfaced in the continued application and development of this family of drugs. These challenges include the emergence of delayed treatment responses to artemisinins in malaria and efforts to apply artemisinins for non-malarial indications. Here, we provide an overview of the story of artemisinin in terms of its past, present, and future. In particular, we comment on the current understanding of the mechanism of action (MOA) of artemisinins, and emphasize the importance of relating mechanistic studies to therapeutic outcomes, both in malarial and non-malarial contexts. 展开更多
关键词 ARTEMISININ Mechanism of action MALARIA ANTI-CANCER
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Induction of apoptosis by artemisinin relieving the severity of inflammation in caerulein-induced acute pancreatitis 被引量:14
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作者 Ming Zhao Dong-Bo Xue +3 位作者 Biao Zheng Wei-Hui Zhang Shang-Ha Pan Bei Sun 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第42期5612-5617,共6页
AIM: To observe the apoptosis and oncosis of pancreatic acinar cells and secondary inflammatory reaction in pancreatic tissue from rats with acute pancreatitis (AP), and the influences of artemisinin on them.METHOD... AIM: To observe the apoptosis and oncosis of pancreatic acinar cells and secondary inflammatory reaction in pancreatic tissue from rats with acute pancreatitis (AP), and the influences of artemisinin on them.METHODS: AP was induced by 4 intraperitoneal iojections of caerulein at 1 h intervals. To induce apoptosis, solution of artemisinin (50 mg/kg) was given intraperitoneally 1, 12, 24 and 36 h after the last caerulein injection. Histological examination of impairment of pancreatic tissue and detection of serum amylase were performed to evaluate the severity of acute pancreatitis. Apoptosis and oncosis were detected with acridine orange (AO) and ethylene dibromide (EB) staining. Caspase-3 and myeloperoxidase (MPO) activity were measured by colorimetric assay. Nuclear factor-kappa B (NF-KB) activation was detected by flow cytometry. Macrophage inflammatory protein-lα(MIP-1α) protein was measured by Western blot. Interleukin- 1β(IL-1β) mRNA was detected by RT-PCR.RESULTS: Addition of artemisinin increased the number of apoptotic cells (11.7%±1.4% vs 6.3%± 0.7%, P 〈 0.05), while reduced the number of oncotic cells (13.0% ±2.4% vs 17.5%±2.2%, P 〈 0.05). The activity of caspase-3 speeded up (1.52±0.21 vs 1.03±0.08, P 〈 0.05), the pancreas pathological impairment was relieved (3.0±0.5 vs 4.0± 0.5, P 〈 0.05) and the level of serum amylase decreased (5642±721 U/dL vs 7821±653 U/dL, P 〈 0.05). The activation of NF-1α (29%±4.1% vs 42%±5.8%), MIP-1α protein (3.7±0.5 vs 5.8±0.7),MPO (0.52±0.06 U/g vs 0.68±0.09 U/g), IL-1β mRNA (1.7 ±0.3 vs 2.4 ±0.4) in the apoptosis inducing group was obviously decreased (P 〈 0.05).CONCLUSION: Inducing apoptosis can relieve pathological impairment and inflammatory reaction in AP rats. 展开更多
关键词 PANCREATITIS APOPTOSIS Inflammation mediators CHEMOKINES ARTEMISININ
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Antitumor Research on Artemisinin and Its Bioactive Derivatives 被引量:8
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作者 Yunqin Zhang Guowei Xu +3 位作者 Shuqun Zhang Dong Wang PSaravana Prabha Zhili Zuo 《Natural Products and Bioprospecting》 CAS 2018年第4期303-319,共17页
Cancer is the leading cause of human death which seriously threatens human life.The antimalarial drug artemisinin and its derivatives have been discovered with considerable anticancer properties.Simultaneously,a varie... Cancer is the leading cause of human death which seriously threatens human life.The antimalarial drug artemisinin and its derivatives have been discovered with considerable anticancer properties.Simultaneously,a variety of target-selective artemisinin-related compounds with high efficiency have been discovered.Many researches indicated that artemisinin-related compounds have cytotoxic effects against a variety of cancer cells through pleiotropic effects,including inhibiting the proliferation of tumor cells,promoting apoptosis,inducing cell cycle arrest,disrupting cancer invasion and metastasis,preventing angiogenesis,mediating the tumor-related signaling pathways,and regulating tumor microenvironment.More importantly,artemisinins demonstrated minor side effects to normal cells and manifested the ability to overcome multidrug-resistance which is widely observed in cancer patients.Therefore,we concentrated on the new advances and development of artemisinin and its derivatives as potential antitumor agents in recent 5 years.It is our hope that this review could be helpful for further exploration of novel artemisinin-related antitumor agents. 展开更多
关键词 ARTEMISININ Artemisinin derivatives ANTITUMOR ACTIVITY MECHANISM
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Potential applications of artemisinins in ocular diseases 被引量:8
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作者 Bing-Wen Lu Li-Ke Xie 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2019年第11期1793-1800,共8页
Artemisinin, also named qinghaosu, is a family of sesquiterpene trioxane lactone originally derived from the sweet wormwood plant(Artemisia annua), which is a traditional Chinese herb that has been universally used as... Artemisinin, also named qinghaosu, is a family of sesquiterpene trioxane lactone originally derived from the sweet wormwood plant(Artemisia annua), which is a traditional Chinese herb that has been universally used as anti-malarial agents for many years. Evidence has accumulated during the past few years which demonstrated the protective effects of artemisinin and its derivatives(artemisinins) in several other diseases beyond malaria, including cancers, autoimmune disorders, inflammatory diseases, viral and other parasiterelated infections. Recently, this long-considered antimalarial agent has been proved to possess anti-oxidant, anti-inflammatory, anti-apoptotic and anti-excitotoxic properties, which make it a potential treatment option for the ocular environment. In this review, we first described the overview of artemisinins, highlighting the activity of artemisinins to other diseases beyond malaria and the mechanisms of these actions. We then emphasized the main points of published results of using artemisinins in targeting ocular disorders, including uveitis, retinoblastoma, retinal neurodegenerative diseases and ocular neovascularization. To conclude, we believe that artemisinins could also be used as a promising therapeutic drug for ocular diseases, especially retinal vascular diseases in the near future. 展开更多
关键词 ARTEMISININS UVEITIS RETINOBLASTOMA retinal NEURODEGENERATIVE diseases OCULAR NEOVASCULARIZATION
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Differential Effect of Artemisinin Against Cancer Cell Lines 被引量:8
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作者 Mounir Tilaoui Hassan Ait Mouse +1 位作者 Abdeslam Jaafari Abdelmajid Zyad 《Natural Products and Bioprospecting》 CAS 2014年第3期189-196,共8页
The present study aims at defining the differential cytotoxicity effect of artemisinin toward P815(murin mastocytoma)and BSR(kidney adenocarcinoma of hamster)cell lines.Cytotoxicity was measured by the growth inhibit... The present study aims at defining the differential cytotoxicity effect of artemisinin toward P815(murin mastocytoma)and BSR(kidney adenocarcinoma of hamster)cell lines.Cytotoxicity was measured by the growth inhibition using MTT assay.These in vitro cytotoxicity studies were complemented by the determination of apoptotic DNA fragmentation and Annexin V-streptavidin-FITC assay.Furthermore,we examined the in vitro synergism between artemisinin and the chemotherapeutic drug,vincristin.The in vivo study was investigated using the DBA2/P815(H2d)mouse model.While artemisinin acted on both tumor cell lines,P815 was much more sensitive to this drug than BSR cells,as revealed by the respective IC50 values(12 lM for P815 and 52 lM for BSR cells).On another hand,and interestingly,apoptosis was induced in P815 but not induced in BSR.These data,reveal an interesting differential cytotoxic effect,suggesting the existence of different molecular interactions between artemisinin and the studied cell lines.In vivo,our results clearly showed that the oral administration of artemisinin inhibited solid tumor development.Our study demonstrates that artemisinin caused differential cytotoxic effects depending not only on the concentration and time of exposure but also on the target cells. 展开更多
关键词 ARTEMISININ CYTOTOXICITY Apoptosis/necrosis Synergism Antitumor activity
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Artemisinin resistance or tolerance in human malaria patients 被引量:4
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作者 Jerapan Krungkrai Waranya Imprasittichai +2 位作者 Sumintra Otjungreed Sawirasagee Pongsabut Sudaratana R Krungkrai 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2010年第9期748-753,共6页
Malaria is a major cause of morbidity and mortality in the developing world.This situation is mainly due to emergence of resistance to most antimalarial drugs currently available. Artemisinin-based combination treatme... Malaria is a major cause of morbidity and mortality in the developing world.This situation is mainly due to emergence of resistance to most antimalarial drugs currently available. Artemisinin-based combination treatments are now first-line drugs for Plasmodium falciparum (P.falciparum) malaria.Artemisinin(qinghaosu) and its derivatives are the most rapid acting and efficacious antimalarial drugs.This review highlights most recent investigations into the emergence of artemisinin resistance in falciparum malaria patients on the Thai-Cambodian border,a historical epicenter for multidrug resistance spread spanning over 50 years.The study presents the first evidence that highlights the parasites reduced susceptibility to artemisinin treatment by prolonged parasite-clearance times,raising considerable concern on resistance development.Although the exact mechanism of action remains unresolved,development of resistance was proposed based from both in vitro experiments and human patients.Lines of evidence suggested that the parasites in the patients are in dormant forms,presumably tolerate to the drug pressure.The World Health Organization has launched for prevention and/or containment of the artemisinin-resistant malaria parasites.Taken together,the emergence of artemisinin resistance to the most potent antidote for falciparum malaria,poses a serious threat to global malaria control and prompts renewed efforts for urgent development of new antimalarial weapons. 展开更多
关键词 MALARIA PLASMODIUM FALCIPARUM CHEMOTHERAPY ARTEMISININ Drug RESISTANCE
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