Gupta Shreedhara, Raychaudhuri Bikramjit, Banerjee Shouvik, Das Banasri, Mukhopadhaya Sibabrata, Datta Salil C
Department of Biological Chemistry, 4 Raja S. C. Mullick Road, Kolkata, India.
Parasitol Int. 2010 Jun;59(2):192-7. doi: 10.1016/j.parint.2010.01.004. Epub 2010 Feb 1.
Aqueous extract of the green fruits of the Indian plant Momordica charantia and purified Momordicatin structurally established as 4-(o-carboethoxyphenyl) butanol were evaluated in vitro and in vivo against kala-azar caused by Leishmania donovani. 50% inhibitory concentration (IC(50)) against Leishmania promastigotes in vitro for the crude extract and momordicatin were 0.6mg/L and 0.02mg/L, respectively. When administered in the hamster model of visceral leishmaniasis, 100% parasite clearance was achieved at a dose of 300mg/kg body weight of crude extract and 10mg/kg body weight of Momordicatin. Fe containing parasite superoxide dismutase (SOD) was totally inhibited when treated with 0.72mg/L crude extract and 0.20mg/L Momordicatin, respectively, whereas Cu-Zn containing SOD present in host remained unaffected. Results reveal that the mode of action of these newly found antileishmanial agents is mediated through inhibiting parasite SOD which is one of the key enzymes of the oxidative burst. It may be proposed from the present study that both crude extract of Momordica charantia and Momordicatin obtained from the fruits of the said plant may be considered as potential candidates towards developing new chemotherapeutics against leishmaniasis.
对印度植物苦瓜绿色果实的水提取物以及结构确定为4-(邻乙氧羰基苯基)丁醇的纯化苦瓜素进行了体外和体内抗杜氏利什曼原虫引起的黑热病评估。粗提物和苦瓜素对利什曼原鞭毛虫的体外50%抑制浓度(IC50)分别为0.6mg/L和0.02mg/L。在内脏利什曼病的仓鼠模型中给药时，粗提物剂量为300mg/kg体重、苦瓜素剂量为10mg/kg体重时实现了100%的寄生虫清除率。含铁的寄生虫超氧化物歧化酶(SOD)分别用0.72mg/L粗提物和0.20mg/L苦瓜素处理时被完全抑制，而宿主中含铜锌的SOD不受影响。结果表明，这些新发现的抗利什曼原虫药物的作用方式是通过抑制寄生虫SOD介导的，SOD是氧化爆发的关键酶之一。从本研究可以推测，苦瓜的粗提物和从该植物果实中获得的苦瓜素都可被视为开发抗利什曼病新化疗药物的潜在候选物。
