Centre National de Recherche et de Formation sur le Paludisme, 01 BP 2208, Ouagadougou 01, Burkina Faso, France,
Parasitol Res. 2014 Jan;113(1):405-16. doi: 10.1007/s00436-013-3669-8. Epub 2013 Dec 8.
Malaria remains a major public health problem due to the emergence and spread of Plasmodium falciparum drug resistance. There is an urgent need to investigate new sources of antimalarial drugs which are more effective against Plasmodium falciparum. One of the potential sources of antimalarial drugs is traditional medicinal plants. In this work, we studied the in vitro antiplasmodial activity of chloromethylenic, methanolic, and MeOH/H2O (1/1) crude extracts and decoction obtained from eight medicinal plants collected in Burkina Faso and of total alkaloids for five plants. Extracts were evaluated in vitro for efficacy against Plasmodium falciparum strain K1, which is resistant to chloroquine, pyrimethamine and proguanil using the fluorescence-based SYBR Green I assay. The antiproliferative activity on human-derived hepatoma cell line HepG2 and Chinese hamster ovary (CHO) cells was evaluated using the 3-[4,5-dimethylthyazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test in order to determine the selectivity index. Among the plant extracts tested for in vitro antiplasmodial activity, 16 were considered to be inactive (with IC50 > 10 μg/ml), six showed a moderate activity (5 < IC50 ≤ 10 μg/ml), and six were found to have a good in vitro activity with IC50 value ≤ 5 μg/ml. The highest antiplasmodial activity was found for extracts from: the alkaloid leaf extract and the chloromethylenic extracts of Combretum fragrans (IC50 = 3 μg/ml, IC50 = 5 μg/ml), the total alkaloids and the chloromethylenic leaf extracts of Combretum collinum (IC50 = 4 μg/ml), the MeOH/H2O leaf extract of Terminalia avicennioides (IC50 = 3.5 μg/ml), and the alkaloid leaf extract of Pavetta crassipes (IC50 = 5 μg/ml). Three other extracts showed moderate antiplasmodial activity (5 < IC50 ≤ 10 μg/ml): Terminalia avicennioides and Combretum fragrans methanolic extracts and Acacia kirkii alkaloid leaf extract (IC50 = 6.5, 9 and 10 μg/ml respectively). The Terminalia avicennioides crude MeOH/H2O (80:20 v/v) extract of the leaves was submitted to a successive liquid/liquid extraction with ethylacetate and n-butanol respectively. The extracts were investigated for in vitro antiplasmodial activity and antioxidant properties using DPPH(·), ABTS(+) and FRAP methods. The ethylacetate extract showed the best antiplasmodial activity (7 μg/ml) and the active constituent was isolated as ellagic acid by bioguided fractionation with an IC50 = 0.2 μM on Plasmodium falciparum and SI = 152. Besides, Terminalia avicennioides leaf extract and ellagic acid showed a good antioxidant activity. Our finding confirms the importance of investigating the antimalarial activity of plant species used in traditional medicine. Overall, two plants belonging to the Combretaceae family, Combretum fragrans and Combretum collinum appeared to be the best candidates and will be further investigated for their antiplasmodial properties, in order to isolate the molecules responsible for the antiplasmodial activity.
疟疾仍然是一个主要的公共卫生问题,这是由于恶性疟原虫耐药性的出现和传播。因此,迫切需要寻找更有效的抗疟药物新来源,其中包括传统药用植物。在这项工作中,我们研究了从布基纳法索采集的八种药用植物的氯亚甲基、甲醇和 MeOH/H2O(1/1)粗提物和浸膏以及五种植物的总生物碱的体外抗疟活性。使用基于荧光的 SYBR Green I 测定法,评估提取物对氯喹、甲氨蝶呤和氨苯砜耐药的恶性疟原虫 K1 株的疗效。使用 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四唑溴盐(MTT)试验评估对人源性肝癌细胞系 HepG2 和中国仓鼠卵巢(CHO)细胞的增殖抑制活性,以确定选择性指数。在测试的具有体外抗疟活性的植物提取物中,有 16 种被认为是无效的(IC50 > 10 μg/ml),6 种表现出中等活性(5 < IC50 ≤ 10 μg/ml),6 种被发现具有良好的体外活性,IC50 值≤ 5 μg/ml。发现具有最高抗疟活性的是:Combretum fragrans 的生物碱叶提取物和氯亚甲基提取物(IC50 = 3 μg/ml,IC50 = 5 μg/ml)、Combretum collinum 的总生物碱和氯亚甲基叶提取物(IC50 = 4 μg/ml)、Terminalia avicennioides 的 MeOH/H2O 叶提取物(IC50 = 3.5 μg/ml)和 Pavetta crassipes 的生物碱叶提取物(IC50 = 5 μg/ml)。另外三种提取物显示出中等抗疟活性(5 < IC50 ≤ 10 μg/ml):Terminalia avicennioides 和 Combretum fragrans 的甲醇提取物和 Acacia kirkii 的生物碱叶提取物(IC50 分别为 6.5、9 和 10 μg/ml)。Terminalia avicennioides 的粗 MeOH/H2O(80:20 v/v)叶提取物分别用乙酸乙酯和正丁醇进行连续液/液萃取。使用 DPPH(·)、ABTS(+)和 FRAP 方法评估提取物的体外抗疟活性和抗氧化性能。乙酸乙酯提取物表现出最好的抗疟活性(7 μg/ml),活性成分被鉴定为鞣花酸,其对恶性疟原虫的 IC50 = 0.2 μM,SI = 152。此外,Terminalia avicennioides 叶提取物和鞣花酸表现出良好的抗氧化活性。我们的发现证实了研究在传统医学中使用的植物物种的抗疟活性的重要性。总体而言,两种属于桃金娘科的植物,Combretum fragrans 和 Combretum collinum,似乎是最好的候选植物,将进一步研究它们的抗疟特性,以分离出具有抗疟活性的分子。