Mesia G K, Tona G L, Penge O, Lusakibanza M, Nanga T M, Cimanga R K, Apers S, Van Miert S, Totte J, Pieters L, Vlietinck A J
University of Kinshasa, Faculty of Pharmacy, Democratic Republic of Congo.
Ann Trop Med Parasitol. 2005 Jun;99(4):345-57. doi: 10.1179/136485905X36325.
The antimalarial activities of crude extracts and 17 fractions from the partition of 80%-methanolic extracts of three plants (the stem bark of Croton mubango, the stem bark of Nauclea pobeguinii and the leaves of Pyrenacantha staudtii) used as antimalarial remedies in the Democratic Republic of Congo were studied both in vitro (against Plasmodium falciparum) and in mice infected with Pl. berghei berghei. The toxic effects of dried aqueous extracts of the plants were also investigated, in uninfected mice. The most active crude extracts in vitro, with median inhibitory concentrations (IC(50)) of <1 microg/ml, were found to be the methanolic and dichloromethane extracts of C. mubango, and the dichloromethane extracts of N. pobeguinii and Py. staudtii. The aqueous extract with the most antimalarial activity in vitro was that of C. mubango (IC(50) = 3.2 microg/ml), followed by that of N. probeguinii (IC(50) = 5.3 microg/ml) and then that of Py. staudii (IC(50) = 15.2 microg/ml). Results from the in-vivo tests of antimalarial activity showed that, at a daily oral dose of 200 mg/kg, all the dichloromethane extracts, the petroleum-ether, chloroformic, ethyl-acetate and residual water-soluble fractions from C. mubango, and the chloroformic, ethyl-acetate and n-butanolic fractions from Py. staudtii produced >80% chemosuppression of the parasitaemias by day 4. The aqueous extracts of C. mubango and N. probeguinii produced a slightly lower but still significant inhibition of parasitaemia (60%-80%) whereas that of Py. staudtii only suppressed the day-4 parasitaemias by 37%. The dried aqueous extract of the stem bark of C. mubango showed some signs of toxicity in mice, with median lethal doses (LD(50)) of 350 mg/kg in the female mice and 900 mg/kg in the male. The extract significantly increased the serum concentrations of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) in mice of both sexes, but had no effect on the blood levels of creatinine or urea. No significant toxic effect was observed for the dried aqueous extracts of N. pobeguinii and Py. staudtii (LD(50) >5 g/kg). Neither of these extracts affected the serum concentrations of GPT or the blood concentrations of creatinine and urea, although the N. pobeguinii extract did increase the serum concentration of GOT.
对三种植物（巴豆属穆班戈种的茎皮、诺克莱属波贝吉尼种的茎皮和刺核藤属施陶迪种的叶）80%甲醇提取物进行分离得到的粗提物和17个组分的抗疟活性进行了研究，这些植物在刚果民主共和国被用作抗疟药物。研究在体外（针对恶性疟原虫）和感染伯氏疟原虫的小鼠体内进行。还在未感染的小鼠中研究了这些植物干燥水提取物的毒性作用。体外活性最强的粗提物，其半数抑制浓度（IC50）<1微克/毫升，发现是穆班戈巴豆的甲醇提取物和二氯甲烷提取物，以及波贝吉尼诺克莱和施陶迪刺核藤的二氯甲烷提取物。体外抗疟活性最强的水提取物是穆班戈巴豆的提取物（IC50 = 3.2微克/毫升），其次是波贝吉尼诺克莱的提取物（IC50 = 5.3微克/毫升），然后是施陶迪刺核藤的提取物（IC50 = 15.2微克/毫升）。体内抗疟活性测试结果表明，在每日口服剂量为200毫克/千克时，穆班戈巴豆的所有二氯甲烷提取物、石油醚、氯仿、乙酸乙酯和残留水溶性组分，以及施陶迪刺核藤的氯仿、乙酸乙酯和正丁醇组分在第4天时对疟原虫血症的化学抑制率>80%。穆班戈巴豆和波贝吉尼诺克莱的水提取物对疟原虫血症的抑制作用略低但仍显著（60%-80%），而施陶迪刺核藤的水提取物仅在第4天时将疟原虫血症抑制了37%。穆班戈巴豆茎皮的干燥水提取物在小鼠中显示出一些毒性迹象，雌性小鼠的半数致死剂量（LD50）为350毫克/千克，雄性小鼠为900毫克/千克。该提取物显著提高了雌雄小鼠血清中谷氨酸草酰乙酸转氨酶（GOT）和谷氨酸丙酮酸转氨酶（GPT）的浓度，但对肌酐或尿素的血液水平没有影响。未观察到波贝吉尼诺克莱和施陶迪刺核藤干燥水提取物有显著毒性作用（LD50>5克/千克）。这两种提取物均未影响GPT的血清浓度或肌酐和尿素的血液浓度，尽管波贝吉尼诺克莱提取物确实提高了GOT的血清浓度。
