Efficacy evaluation of traditionally used antimalarial plants

说明（由申请人提供）：每年报告的疟疾病例超过2.5亿例，其中100万例导致死亡。目前，由于广泛的耐药性，没有一种药物能够普遍成功地治疗疟疾；迫切需要新的抗疟药物。氯喹和青蒿素这两种最有效和最广泛使用的抗疟疾药物是从植物中提取的。很可能植物中含有许多更有效但尚未发现的抗疟化合物。默克公司在第二次世界大战期间开展的大规模抗疟筛查项目（Spencer et al . 1947）提供了初步抗疟植物信息的宝贵来源。在那项研究中，88种物种（在600种被测试的物种中）被证明对禽类疟疾毒株有活性，但是近一半（39种）在随后的研究中被忽视了。这些植物为进一步研究抗疟药物提供了有希望的线索。我们的初步研究已经证实了默克公司确定的6种活性中的5种的活性，验证了这项工作的后续工作。

DESCRIPTION (provided by applicant): Over 250 million cases of malaria are reported each year, 1 million of which result in death. Currently, no drugs are universally successful in treating malaria due to widespread drug resistance; new antimalarials are desperately needed. Chloroquine and artemisinin, two of the most effective and widely used antimalarial drugs, are derived from plants. It is likely that plants harbor many more potent and as yet undiscovered antimalarial compounds. A massive antimalarial screening program conducted by Merck during the Second World War (Spencer et al 1947) provides a valuable source of preliminary antimalarial plant information. Eighty eight species (out of 600 tested) were proven active against avian strains of malaria in that study, but nearly half (39) have been neglected in subsequent studies. These plants represent promising leads for further antimalarial inquiry. Our preliminary research has confirmed the activity of 5 of 6 species identified as active by Merck, validating the proposed follow up of this work. The work outlined in this application evaluate the understudied, but promising antimalarial plants identified by Merck's scientists in 1947 using a combination of modern in vitro assay for inhibition of Plasmodium falciparum proliferation in cultured erythrocytes and follow-up in vivo animal studies. State-of-the- art chemical isolation and characterization techniques will be applied to compare and elucidate the composition, chemical identity, and bioactivity of fractions and compounds from antimalarial plant extracts with the highest in vitro activity and low toxicity. These substances will be tested in animal model of malaria using C57Bl mice infected with the Plasmodium berghei strain. This model will also allow synergistic and pharmacodynamic investigations of promising extracts. The relevance of this research application to public health is to support the traditional use of plants used to treat malaria, provide crucial preclinical data for future development of novel antimalarial therapies, and help to elucidate novel biochemical and physiological information about plasmodium-host interactions. By evaluating botanical treatments that might be cultivated locally, used locally, and have local benefits, this scientific work will have broad and long-term impacts both on the global scale as well on the communal scale in the fight against malaria.