Institute of Life Sciences, Nalco Square, Chandrasekhar Pur, Bhubaneswar 751 023, Orissa, India.
Exp Parasitol. 2010 Apr;124(4):421-7. doi: 10.1016/j.exppara.2009.12.007. Epub 2009 Dec 29.
Quassia amara L. (Family Simaroubaceae) is known to have several medicinal properties including the activity against malaria. An HPLC method was employed for purification of the biologically active quassinoids; quassin (Q) and neo-quassin (NQ), further characterized by MALDI-TOF analyses. Purified Q, NQ and the crude bark extract (S1) along with artesunate (AS) were studied for their in vitro anti-plasmodial activity. The in vivo toxicity studies at intraperitoneal doses with higher concentrations of the crude bark extract (S1) in Balb/C mice ruled out the apprehension of toxicity. Interaction studies between the test compounds among themselves (Q+NQ) and individually with artesunate (AS+Q, AS+NQ), were carried out in vitro at four ratios (1:5, 1:2, 2:1 and 5:1) on chloroquine sensitive (MRC-pf-20) and resistant (MRC-pf-303) strains of Plasmodium falciparum. The crude bark extracts of Q. amara exhibited higher P. falciparum inhibitory activity (IC(50)=0.0025 microg/ml) as compared to that of the isolated compounds, quassin (IC(50)=0.06 microg/ml, 0.15 microM), neo-quassin (IC(50)=0.04 microg/ml, 0.1 microM) and also to the positive control, artesunate (IC(50)=0.02 microg/ml, 0.05 microM). The in vitro drug interaction study revealed the compounds, quassin and neo-quassin to be additive to each other. At lower ratios, artesunate was found to be a potential combination partner with both the compounds. It was interesting to note that none of the combinations exhibited antagonistic interactions. This phenomenon offers the opportunity for further exploration of novel therapeutic concentrations and combinations.
苦木（Family Simaroubaceae）已知具有多种药用特性，包括抗疟疾活性。采用 HPLC 法对具有生物活性的苦木苦味素进行纯化；苦木素（Q）和新苦木素（NQ），进一步通过 MALDI-TOF 分析进行表征。对纯化的 Q、NQ 和粗树皮提取物（S1）以及青蒿琥酯（AS）进行了体外抗疟原虫活性研究。在腹腔内给予更高浓度的粗树皮提取物（S1）的体内毒性研究排除了毒性的担忧。在体外，在四种比例（1:5、1:2、2:1 和 5:1）下，对测试化合物相互之间（Q+NQ）以及与青蒿琥酯（AS+Q、AS+NQ）之间的相互作用进行了研究在氯喹敏感（MRC-pf-20）和耐药（MRC-pf-303）株疟原虫上。与分离的化合物苦木素（IC50=0.06μg/ml，0.15μM）、新苦木素（IC50=0.04μg/ml，0.1μM）和阳性对照青蒿琥酯（IC50=0.02μg/ml，0.05μM）相比，苦木的粗树皮提取物对疟原虫的抑制活性更高（IC50=0.0025μg/ml）。体外药物相互作用研究表明，化合物苦木素和新苦木素相互之间为相加作用。在较低的比例下，青蒿琥酯被发现是与这两种化合物的潜在组合伙伴。有趣的是，没有一种组合表现出拮抗相互作用。这种现象为进一步探索新的治疗浓度和组合提供了机会。
