Natural products from Zanthoxylum heitzii with potent activity against the malaria parasite

Abstract

BackgroundZanthoxylum heitzii (Rutaceae) (olon) is used in traditional medicine in Central and West Africa to treat malaria. To identify novel compounds with anti-parasitic activity and validate medicinal usage, extracts and compounds isolated from this tree were tested against the erythrocytic stages of the human malaria parasite Plasmodium falciparum and for inhibition of transmission in rodent malaria parasite Plasmodium berghei.ResultsHexane bark extract showed activity against P. falciparum (IC50 0.050 μg/ml), while leaf and seed extracts were inactive. Fractionation of the hexane bark extract led to the identification of three active constituents; dihydronitidine, pellitories and heitziquinone. Dihydronitidine was the most active compound with an IC50 value of 0.0089 µg/ml (25 nM). This compound was slow acting, requiring 50 % longer exposure time than standard anti-malarials to reach full efficacy. Heitziquinone and pellitorine were less potent, with IC50 values of 3.55 μg/ml and 1.96 µg/ml, but were fast-acting. Plasmodium berghei ookinete conversion was also inhibited by the hexane extract (IC50 1.75 µg/ml), dihydronitidine (0.59 µg/ml) and heitziquinone (6.2 µg/ml). Water extracts of Z. heitzii bark contain only low levels of dihydronitidine and show modest anti-parasitic activity.ConclusionsThree compounds with anti-parasitic activity were identified in Z. heitzii bark extract. The alkaloid dihydronitidine is the most effective of these, accounting for the bulk of activity in both erythrocytic and transmission-blocking assays. These compounds may present good leads for development of novel anti-malarials and add to the understanding of the chemical basis of the anti-parasitic activity in these classes of natural product.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1533-x) contains supplementary material, which is available to authorized users.

Anti-plasmodial Effects of Zanthoxylum zanthoxyloides

“…Due to insufficient amounts available, we were unable to test arnottianamide, burkinabin C, 6-hydroxy-dihydrochelerythine, dictamnine, and scoparone. Sesamin was tested by us previously [25] in the same assay system as in this investigation and was found to be inactive [25]. Dictamnine [34] and scoparone [35] have also been found inactive, and the others appear untested.…”

“…Bis-dihydrochelerythrinyl ether, buesgenine, chelerythrine, γfagarine, and skimmianin were identified as compounds from Z. zanthoxyloides with activity against P. falciparum 3D7 (▶ Table 1). Pellitorine had recently been isolated from the related plant Z. heitzii and was found by us to have an IC 50 value of 2.0 ± 0.1 µg/mL (8.8 ± 0.5 µM) using an identical assay [25]. Therefore, it was not retested in the present investigation.…”

“…The objective of the present project was to further characterize the chemical composition of Z. zanthoxyloides, and to evaluate the anti-Plasmodium effects and brine shrimp toxicity of extracts and isolated compounds. This project is a follow-up to our previous work on anti-plasmodial components in Zanthoxylum heitzii [25].…”

“…In vitro cultures of P. falciparum were maintained by standard methods [39] in human blood (a kind gift of the Australian Red Cross Blood Service). Assays were carried out as described previously [25] using a 96-well in vitro assay based on the SYBRgreen method of Smilkstein et al [40] as modified by Goodman et al [41]. Isolated compounds present in sufficient amounts were chosen for screening of anti-parasitic activity.…”

Erratum to: Natural products from Zanthoxylum heitzii with potent activity against the malaria parasite

“…After publication of the original article [1], it came to the authors’ attention that an error in the abstract was introduced during production of the article. In the Results section of the abstract, ‘pellitorine’ appears incorrectly as ‘pellitories’.…”