从防己科植物苦玄参的树皮中分离得到的甾体生物碱 conessine 具有抗疟作用。
Anti-malarial property of steroidal alkaloid conessine isolated from the bark of Holarrhena antidysenterica.
机构信息
Field Unit, Sector-3, Health Centre, BHEL, National Institute of Malaria Research, Hardwar 249403, India.
出版信息
Malar J. 2013 Jun 10;12:194. doi: 10.1186/1475-2875-12-194.
BACKGROUND
In the face of chronic and emerging resistance of parasites to currently available drugs and constant need for new anti-malarials, natural plant products have been the bastion of anti-malarials for thousands of years. Moreover natural plant products and their derivatives have traditionally been a common source of drugs, and represent more than 30% of the current pharmaceutical market. The present study shows evaluation of anti-malarial effects of compound conessine isolated from plant Holarrhena antidysenterica frequently used against malaria in the Garhwal region of north-west Himalaya.
METHODS
In vitro anti-plasmodial activity of compound was assessed using schizont maturation and parasite lactate dehydrogenase (pLDH) assay. Cytotoxic activities of the examined compound were determined on L-6 cells of rat skeletal muscle myoblast. The four-day test for anti-malarial activity against a chloroquine-sensitive Plasmodium berghei NK65 strain in BALB/c mice was used for monitoring in vivo activity of compound. In liver and kidney function test, the activity of alkaline phosphatase (ALP) was examined by p-NPP method, bilirubin by Jendrassik and Grof method. The urea percentage was determined by modified Berthelot method and creatinine by alkaline picrate method in serum of mice using ENZOPAK/CHEMPAK reagent kits.
RESULTS
Compound conessine showed in vitro anti-plasmodial activity with its IC₅₀ value 1.9 μg/ml and 1.3 μg/ml using schizont maturation and pLDH assay respectively. The compound showed cytotoxity IC₅₀= 14 μg/ml against L6 cells of rat skeletal muscle myoblast. The isolated compound from plant H. antidysenterica significantly reduced parasitaemia (at 10 mg/kg exhibited 88.95% parasite inhibition) in P. berghei-infected mice. Due to slightly toxic nature (cytotoxicity = 14), biochemical analysis (liver and kidney function test) of the serum from mice after administration of conessine were also observed.
CONCLUSION
The present investigation demonstrates that the compound conessine exhibited substantial anti-malarial property. The isolated compound could be chemically modified to obtain a more potent chemical entity with improved characteristics against malaria.
背景
面对寄生虫对现有药物的慢性和新兴耐药性以及对新抗疟药物的持续需求，天然植物产品数千年来一直是抗疟药物的堡垒。此外，天然植物产品及其衍生物一直是药物的常见来源，占当前药物市场的 30%以上。本研究显示了从常用于西北喜马拉雅山 Garhwal 地区疟疾的植物 Holarrhena antidysenterica 中分离得到的化合物康西宁的抗疟效果评价。
方法
使用裂殖体成熟和寄生虫乳酸脱氢酶（pLDH）测定法评估化合物的体外抗疟活性。在所检查的化合物对大鼠骨骼肌成肌细胞 L-6 细胞的细胞毒性活性进行了测定。使用抗氯喹敏感伯氏疟原虫 NK65 株在 BALB/c 小鼠中的四天抗疟活性试验监测化合物的体内活性。在肝肾功能试验中，通过 p-NPP 法测定碱性磷酸酶（ALP）的活性，通过 Jendrassik 和 Grof 法测定胆红素，通过改良 Berthelot 法测定血清中的尿素百分比，通过碱性苦味酸法测定肌酐使用 ENZOPAK/CHEMPAK 试剂试剂盒。
结果
化合物康西宁在裂殖体成熟和 pLDH 测定中，IC₅₀值分别为 1.9 μg/ml 和 1.3 μg/ml，显示出体外抗疟活性。该化合物对大鼠骨骼肌成肌细胞 L6 细胞的细胞毒性 IC₅₀=14μg/ml。从植物 H. antidysenterica 中分离得到的化合物可显著降低伯氏疟原虫感染小鼠的寄生虫血症（在 10mg/kg 时表现出 88.95%的寄生虫抑制作用）。由于具有轻微的毒性（细胞毒性=14），还观察了给药后小鼠血清的生化分析（肝肾功能试验）。
结论
本研究表明，化合物康西宁表现出显著的抗疟特性。该分离化合物可以进行化学修饰，以获得具有改善的抗疟疾特性的更有效化学实体。
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