Onaku L O, Attama A A, Okore V C, Tijani A Y, Ngene A A, Esimone C O
Department of Pharmaceutics, University of Nigeria, Nsukka, Nigeria.
J Vector Borne Dis. 2011 Jun;48(2):96-100.
BACKGROUND & OBJECTIVES: Artemisinins, the main stay in the treatment of malaria are used in combinations with other antimalarials to forestall resistance, as artemisinin-combination therapies (ACTs). However, ACTs are expensive and some of the non-artemisinin components are not well-tolerated by patients. There are several folkloric and scientific proofs of the efficacy of herbal remedies for malaria. Mature leaves of Carica papaya is widely used to treat malaria in several African countries. An ACT involving a medicinal herb extract or its active constituent(s) will provide an indigenous alternative/herbal ACT.
Mature fresh leaves of Carica papaya were grounded and macerated in cold distilled water for 24 h and the extract (PCE) was stored in the refrigerator for seven days. Fresh extracts were made as needed. The antiplasmodial activity of PCE and/or artesunic acid were determined by using the Peter's 4-day suppressive test in Plasmodium berghei-infected mice. The ED50 and ED90 were calculated from the dose-response relationships.
The combination of 50 mg/kg of PCE and 15 mg/kg of artesunic acid produced a significant reduction of parasitemia (81.25%), compared to 50 mg/kg PCE alone (37.7%). The mean survival time of the combinations of PCE and 15 mg/kg of artesunic acid, and PCE alone followed a dose-dependent manner. The ED50 of PCE showed that it has a very good activity. The isobolar equivalent (IE) calculated from the ED90 of PCE in combination with artesunic acid showed that the interaction was antagonistic.
INTERPRETATION & CONCLUSION: Although pawpaw alone was found to have a very good activity, its combination with artesunic acid is antagonistic. Combinations of artemisinins and pawpaw show little promise for combination therapy development.
青蒿素是疟疾治疗的主要药物，通常与其他抗疟药联合使用以预防耐药性，即青蒿素联合疗法（ACTs）。然而，ACTs价格昂贵，且一些非青蒿素成分患者耐受性不佳。有多种民间和科学证据表明草药对疟疾有效。番木瓜成熟叶在多个非洲国家被广泛用于治疗疟疾。一种包含草药提取物或其活性成分的ACT将提供一种本土替代方案/草药ACT。
将番木瓜成熟鲜叶研磨并在冷蒸馏水中浸泡24小时，提取物（PCE）在冰箱中保存7天。根据需要制备新鲜提取物。通过对感染伯氏疟原虫的小鼠进行彼得4天抑制试验，测定PCE和/或青蒿琥酯的抗疟活性。根据剂量反应关系计算半数有效剂量（ED50）和90%有效剂量（ED90）。
与单独使用50mg/kg PCE（37.7%）相比，50mg/kg PCE与15mg/kg青蒿琥酯联合使用可使疟原虫血症显著降低（81.25%）。PCE与15mg/kg青蒿琥酯联合使用以及单独使用PCE的平均存活时间呈剂量依赖性。PCE的ED50表明其具有非常好的活性。根据PCE与青蒿琥酯联合使用的ED90计算的等效线图显示二者相互作用为拮抗作用。
尽管发现单独使用番木瓜具有很好的活性，但其与青蒿琥酯联合使用具有拮抗作用。青蒿素与番木瓜联合用于联合疗法开发前景渺茫。
