The scientists have been working with both water-based and alcohol-based extracts from the bark of the two trees, and it turns out that the extracts with alcohol contains more of the active substances. The substance that kills the mosquito is called pellitorine and was found in the bark of both trees, Malterud explains.
“The Master student Nastaran Moussavi managed to isolate pellitorine and several other substances in extracts from the bark of the Olon tree. Later, she travelled to the French research institute IRD in Montpellier(link is external), in order to study their insecticidal effects. IRD has experts in cultivating the malaria mosquito Anopheles gambiae for scientific studies. Moussavi applied substances from the bark of the Olon tree to the neck of the mosquitoes, in order to investigate if the substances had toxic effects”, Wangensteen explains. “This caused the mosquitos to die, literally as flies! The experiments showed that pellitorine is toxic to mosquitoes”, Malterud adds.
“We also found that a mixture of four main substances from the bark of the Olon tree had a higher toxicity than pellitorine alone, even if the other ingredients were not toxic separately. This suggests that there is a synergistic effect between the ingredients, says Wangensteen.
At this point, Malterud and Wangensteen suspected that the Olon tree contained even more compounds with interesting effects. Then postdoc Ingvild Austarheim contacted the School of BioSciences at the University of Melbourne in Australia, because they have a laboratory with experts on studying the malaria parasite. The scientists in Melbourne were interested in testing the new potential drugs, and it soon turned out that one of the ingredients was very effective in killing the parasite. “But this was not the same compound that killed the mosquitoes! The parasite-killing compound is called dihydronitidine and is a relatively simple alkaloid”, says Wangensteen.
The Norwegian scientists had now shown that the bark of the Olon tree from Congo contains at least two interesting compounds: Pellitorine that kills malaria mosquitoes, and dihydronitidin that kills the malaria parasite. The researchers then went on to test the bark from Zanthoxylum zanthoxyloides, which is related to the Olon tree and is native to Mali. Professor emerita Berit Smestad Paulsen from the School of Pharmacy has cooperated for several years with healers from Mali, and they knew that the bark of this tree had been used in the treatment of malaria patients.
“We found pellitorine also in the bark from this tree, in addition to several other interesting substances that have effects on the malaria parasite. But the effects were smaller than the ones we found in the extracts from the Olon tree”, Wangensteen explains. Both pellitorine and dihydronitidine are chemical substances that were previously known from other plants. However, the powerful effects against malaria mosquitoes and the parasites were little known before the Norwegian scientists started their work.
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