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1.
《结合医学学报(英文版)》2014,12(6):504-511
OBJECTIVE: Phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fi bre of Dwarf Red variety of Cocos nucifera were evaluated in this study.METHODS: The dried powdered husk fi bre was exhaustively extracted with hexane, ethyl acetate and methanol successively and the methanolic extract was screened for fl avonoids, phenolics, tannins, alkaloids, steroids, triterpenes, phlobatannins, anthraquinones and glycosides. A 4-day suppressive antimalarial test was carried out using Plasmodium berghei NK65-infected mice, to which the extract was administered at doses of 31.25, 62.5, 125, 250 and 500 mg/kg body weight(BW). Toxicity of the extract was evaluated in rats using selected hematological parameters and organ function indices after orally administering doses of 25, 50 and 100 mg/kg BW for 14 d.RESULTS: Phytochemical analysis revealed the presence of alkaloids, tannins, phenolics, saponins, glycosides, steroids and anthraquinones in the extract. Moreover, the extract reduced parasitemia by 39.2% and 45.8% at doses of 250 and 500 mg/kg BW respectively on day 8 post-inoculation. Various hematological parameters evaluated were not significantly altered(P0.05) at all doses of the extract, except red blood cell count which was signifi cantly elevated(P0.05) at 100 mg/kg BW. The extract significantly increased(P0.05) urea, creatinine, cholesterol, high-density lipoprotein-cholesterol and bilirubin concentrations in the serum as well as atherogenic index, while it reduced albumin concentration significantly(P0.05) at higher doses compared to the controls. Alanine aminotransferase activity was reduced in the liver and heart signifi cantly(P0.05) but was increased in the serum signifi cantly(P0.05) at higher doses of the extract compared to the controls.CONCLUSION: The results suggest that methanolic extract of the Dwarf red variety has partial antimalarial activity at higher doses, but is capable of impairing normal kidney and liver function as well as predisposing subjects to cardiovascular diseases. 相似文献
2.
恶性疟原虫对青蒿酯钠抗性的体外培育 总被引:3,自引:1,他引:3
江钢锋 《中国寄生虫学与寄生虫病杂志》1992,10(1):37-39
恶性疟原虫FCR_3在体外采用剂量递增间隔接触方法在青篙酯钠的作用下产生了对该药的抗药性。在接触药物前,青蒿酯钠对该虫株裂殖体成熟抑制的半数抑制浓度(IC_(50))为1.6ng/ml(4.1nmol/L),经过130d间隔接触药物后,虫株对青蒿酯钠的敏感性下降,其IC_(50)值增高至约为亲代系的3倍,即4.7ng/ml(12.2nmol/L)。抗性系在去除药物作用后,其抗性水平很快下降。 相似文献
3.
4.
Poonam Yash Gupta Nikesh Gupta Snigdha Singh Lidong Wu Bhupender Singh Chhikara Manmeet Rawat Brijesh Rathi 《Medicinal research reviews》2018,38(5):1511-1535
Over time, several exciting advances have been made in the treatment and prevention of malaria; however, this devastating disease continues to be a major global health problem and affects millions of people every year. Notably, the paucity of new efficient drug molecules and the inevitable drug resistance of the malaria parasite, Plasmodium falciparum, against frontline therapeutics are the foremost struggles facing malaria eradication initiatives. According to the malaria eradication agenda, the discovery of new chemical entities that can destroy the parasite at the liver stage, the asexual blood stage, the gametocyte stage, and the insect ookinete stage of the parasite life cycle (i.e., compounds exhibiting multistage activity) are in high demand, preferably with novel and multiple modes of action. Phenotypic screening of chemical libraries against the malaria parasite is certainly a crucial step toward overcoming these crises. In the last few years, various research groups, including industrial research laboratories, have performed large‐scale phenotypic screenings that have identified a wealth of chemical entities active against multiple life stages of the malaria parasite. Vital scientific and technological developments have led to the discovery of multistage inhibitors of the malaria parasite; these compounds, considered highly valuable starting points for subsequent drug discovery and eradication of malaria, are reviewed. 相似文献
5.
我国近几年抗疟药研究新进展 总被引:1,自引:0,他引:1
邓蓉仙 《中国医药工业杂志》1989,20(8):372-376
综述了我国抗疟药研究的新进展。自1985年以来有三种新药和一种制剂在国内注册,它们是:蒿甲醚、青蒿琥酯、本芴醇和青蒿素栓剂;新药萘酚喹和蒿甲醚-本芴醇复方正进行第Ⅱ期临床试验。此外,咯萘啶与其他药物伍用亦取得进展。 相似文献
6.
Rungsihirunrat K Chaijareonkul W Seugorn A Na-Bangchang K Thaithong S 《Acta tropica》2009,109(1):37-40
The relationship between the in vitro susceptibility of Plasmodium falciparum isolates to the quinoline antimalarials chloroquine (CQ), mefloquine (MQ), and quinine (QN), and pfcrt and pfmdr1 gene polymorphisms were investigated. Field isolates (110 samples) were collected from various endemic areas of Thailand throughout 2002-2004. The pfcrt 76T allele was identified in 109 isolates (99.1%) while pfcrt 76K was found in a single (0.9%) isolate. The pfmdr 86N, 86Y, and the combination (86N + 86Y) alleles were identified in 83 (75.5%), 22 (20%), and 5 (4.5%) isolates, respectively. The pfmdr1 1042N, 1042D alleles and a mixture (1042N + 1042D) of the alleles were found in 94 (85.5%), 12 (10.9%) and 4 (3.6%) isolates, respectively. The pfmdr1 1246Y allele was detected in a single (0.9%) isolate. The pfmdr1 gene polymorphisms (86-1042-1246) was grouped into seven haplotypes as follows: N-N-D (68 isolates; 61.2%), Y-N-D (22 isolates; 19.8%), N-D-D (11 isolates; 9.9%), N-D-Y (1 isolate; 0.9%), N/Y-N-D (4 isolates; 3.6%), N-N/D-D (3 isolates; 2.7%), and N/Y-N/D-D (1 isolate; 0.9%). Eight different combinations of pfcrt-pfmdr1 genotypes were observed. Only one CQ-, MQ- and QN-sensitive isolate was found at the Thai-Laos border and no cases of QN resistance were found in this study. 相似文献
7.
目的 观察蒿甲醚伍用伯氨喹治疗恶性疟的疗效和副作用。 方法 在中非共和国选择恶性疟12 1例 ,随机分为两组。伍用组 :口服蒿甲醚 80mg ,qd× 5d ,首日蒿甲醚 16 0mg加服伯氨喹 3片 (含基质 7 5mg ,qd× 3~ 4d)治疗 32例 ;肌注蒿甲醚加服伯氨喹 ,治疗 2 9例 ;对照组 :单用口服蒿甲醚治疗 33例和肌注蒿甲醚治疗 2 7例 ,B组、C组和D组所用剂量与疗程均同A组。上述病例于用药前及后 6、 14、 2 1、及 2 8d各随访1次 ,密切观察病例的临床症状与体征变化。 结果 A组、B组、C组和D组病例的平均退热时间分别为(47 6± 15 7)、 (36 9± 10 7)、 (48 5± 18 4 )和 (42 2± 9 5 )h。其临床治愈率依次为 84 4 %、 10 0 %、 90 1和96 3% ,其复燃率依次为 6 3%、 3 4 %、 2 1 2 %和 18 5 %。 4组药物副作用均轻。 结论 蒿甲醚伍用伯氨喹及单用蒿甲醚 (口服或肌注 )对恶性疟治疗作用均良好 ,但联合使用药物能降低恶性疟的复燃率 相似文献
8.
Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. 总被引:10,自引:0,他引:10
Stanley Mukanganyama Mikael Widersten Yogeshkumar S Naik Bengt Mannervik Julia A Hasler 《International journal of cancer. Journal international du cancer》2002,97(5):700-705
A strategy to overcome multidrug resistance in cancer cells involves treatment with a combination of the antineoplastic agent and a chemomodulator that inhibits the activity of the resistance-causing protein. The aim of our study was to investigate the effects of antimalarial drugs on human recombinant glutathione S-transferase (GSTs) activity in the context of searching for effective and clinically acceptable inhibitors of these enzymes. Human recombinant GSTs heterologously expressed in Escherichia coli were used for inhibition studies. GST A1-1 activity was inhibited by artemisinin with an IC(50) of 6 microM, whilst GST M1-1 was inhibited by quinidine and its diastereoisomer quinine with IC(50)s of 12 microM and 17 microM, respectively. GST M3-3 was inhibited by tetracycline only with an IC(50) of 47 microM. GST P1-1 was the most susceptible enzyme to inhibition by antimalarials with IC(50) values of 1, 2, 1, 4, and 13 microM for pyrimethamine, artemisinin, quinidine, quinine and tetracycline, respectively. The IC(50) values obtained for artemisinin, quinine, quinidine and tetracycline are below peak plasma concentrations obtained during therapy of malaria with these drugs. It seems likely, therefore, that GSTs may be inhibited in vivo at doses normally used in clinical practice. Using the substrate ethacrynic acid, a diuretic drug also used as a modulator to overcome drug resistance in tumour cells, GST P1-1 activity was inhibited by tetracycline, quinine, pyrimethamine and quinidine with IC(50) values of 18, 27, 45 and 70 microM, respectively. The ubiquitous expression of GSTs in different malignancies suggests that the addition of nontoxic reversing agents such as antimalarials could enhance the efficacy of a variety of alkylating agents. 相似文献
9.
Andrea Savarino Mothanje B. Lucia Rob ter Heine Elena Rastrelli Sergio Rutella Giancarlo Majori Alwin Huitema Johan R. Boelaert Roberto Cauda 《Drug development research》2006,67(10):806-817
In this study, the effects of the quinoline antimalarials, chloroquine and mefloquine, were tested on: (1) HIV‐1 replication; (2) virus response to existing antiretrovirals; (3) functional activity of drug efflux pumps; and (4) intracellular accumulation of antiretrovirals. Antiretroviral activity was evaluated using cells acutely infected with drug‐sensitive/resistant HIV‐1 isolates or retroviral vectors, chronically infected cell lines, and syncytium assays. Drug interactions were assessed isobolographically. Activity of efflux pumps was tested using specific fluorochromes. Antitretroviral concentrations were quantitated by HPLC. Results indicated that: (1) the antimalarials (mefloquine > chloroquine) inhibited the replication of drug‐sensitive and drug‐resistant HIV‐1 at therapeutically achievable concentrations and specifically impaired the formation of fusion‐competent viral glycoproteins; (2) anti‐HIV‐1 effects were additive to those of zidovudine and nevirapine, and synergistic to those of lopinavir; (3) the antimalarials (mefloquine > chloroquine) inhibited the P‐glycoprotein, multidrug‐resistance‐associated proteins, and breast‐cancer resistance‐associated protein; (4) Chloroquine, but not mefloquine, increased lopinavir concentrations in peripheral blood mononuclear cells (PBMCs) by approximately 5 (five)‐fold. Thus quinoline antimalarials inhibited HIV‐1 replication by a novel mechanism, resulting in additive or synergistic effects in combination with known antiretrovirals. These drugs may also have an impact on the cellular pharmacokinetics of antiretrovirals. Drug Dev. Res. 67:806–817, 2006. © 2007 Wiley‐Liss, Inc. 相似文献
10.
M. A. Melikoglu MD M. Melikoglu MD U. Gurbuz MD B. S. Budak MD C. Kacar MD 《Journal of clinical pharmacy and therapeutics》2008,33(6):699-701
The antimalarials are one of the most commonly prescribed drugs in medical practice, for conditions such as rheumatoid arthritis as well as malaria. They are generally well‐tolerated and the possible side effects of synthetic antimalarials, though infrequent, are well known. Besides the familiar adverse reactions, a localized mucocutaneous bluish‐grey to black discolouration can sometimes be seen with antimalarial drugs. The aim of this report was to draw attention to the localized mucocutaneous bluish‐grey hyperpigmentation induced by hydroxychloroquine with a case presentation and a review of the literature. 相似文献