Synergism in Antiplasmodial Activities of Artemether and Lumefantrine in Combination with Securidaca longipedunculata Fresen (Polygalaceae)

doi:10.3390/plants11010047

. 2021 Dec 24;11(1):47.

doi: 10.3390/plants11010047.

Synergism in Antiplasmodial Activities of Artemether and Lumefantrine in Combination with Securidaca longipedunculata Fresen (Polygalaceae)

Douglas O Ochora¹, Esezah K Kakudidi¹, Jane Namukobe², Perpetua Ipulet¹, Dancan M Wakoli^{3

4}, Winnie Okore^{4

5}, Edwin W Mwakio⁵, Redempthah A Yeda⁵, Agnes C Cheruiyot⁵, Dennis W Juma⁵, Ben Andagalu⁵, Amanda L Roth⁵, Bernhards R Ogutu⁶, Abiy Yenesew⁷, Hoseah M Akala⁵

Affiliations

¹ Department of Plant Sciences, Microbiology & Biotechnology, College of Natural Sciences, Makerere University, Kampala P.O. Box 7062-10207, Uganda.
² Department of Chemistry, College of Natural Sciences, Makerere University, Kampala P.O. Box 7062-10207, Uganda.
³ Department of Biochemistry and Molecular Biology, Egerton University, Njoro P.O. Box 536-20115, Kenya.
⁴ United States Army Medical Research Directorate-Kenya (USAMRD-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kisumu P.O. Box 54-40100, Kenya.
⁵ Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno P.O. Box Private Bag-40105, Kenya.
⁶ Centre for Clinical Research, Kenya Medical Research Institute (KEMRI), Kisumu P.O. Box 1578-40100, Kenya.
⁷ Department of Chemistry, University of Nairobi, Nairobi P.O. Box 30197-00100, Kenya.

PMID: 35009051
PMCID: PMC8747340
DOI: 10.3390/plants11010047

Synergism in Antiplasmodial Activities of Artemether and Lumefantrine in Combination with Securidaca longipedunculata Fresen (Polygalaceae)

Douglas O Ochora et al. Plants (Basel). 2021.

. 2021 Dec 24;11(1):47.

doi: 10.3390/plants11010047.

Authors

Affiliations

¹ Department of Plant Sciences, Microbiology & Biotechnology, College of Natural Sciences, Makerere University, Kampala P.O. Box 7062-10207, Uganda.
² Department of Chemistry, College of Natural Sciences, Makerere University, Kampala P.O. Box 7062-10207, Uganda.
³ Department of Biochemistry and Molecular Biology, Egerton University, Njoro P.O. Box 536-20115, Kenya.
⁴ United States Army Medical Research Directorate-Kenya (USAMRD-K), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, Kisumu, Kisumu P.O. Box 54-40100, Kenya.
⁵ Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno P.O. Box Private Bag-40105, Kenya.
⁶ Centre for Clinical Research, Kenya Medical Research Institute (KEMRI), Kisumu P.O. Box 1578-40100, Kenya.
⁷ Department of Chemistry, University of Nairobi, Nairobi P.O. Box 30197-00100, Kenya.

PMID: 35009051
PMCID: PMC8747340
DOI: 10.3390/plants11010047

Abstract

Malaria is the most lethal parasitic disease in the world. The frequent emergence of resistance by malaria parasites to any drug is the hallmark of sustained malaria burden. Since the deployment of artemisinin-based combination therapies (ACTs) it is clear that for a sustained fight against malaria, drug combination is one of the strategies toward malaria elimination. In Sub-Saharan Africa where malaria prevalence is the highest, the identification of plants with a novel mechanism of action that is devoid of cross-resistance is a feasible strategy in drug combination therapy. Thus, artemether and lumefantrine were separately combined and tested with extracts of Securidaca longipedunculata, a plant widely used to treat malaria, at fixed extract-drug ratios of 4:1, 3:1, 1:1, 1:2, 1:3, and 1:4. These combinations were tested for antiplasmodial activity against three strains of Plasmodium falciparum (W2, D6, and DD2), and seven field isolates that were characterized for molecular and ex vivo drug resistance profiles. The mean sum of fifty-percent fractional inhibition concentration (FIC₅₀) of each combination and singly was determined. Synergism was observed across all fixed doses when roots extracts were combined with artemether against D6 strain (FIC₅₀ 0.403 ± 0.068) and stems extract combined with lumefantrine against DD2 strain (FIC₅₀ 0.376 ± 0.096) as well as field isolates (FIC₅₀ 0.656 ± 0.067). Similarly, synergism was observed in all ratios when leaves extract were combined with lumefantrine against W2 strain (FIC₅₀ 0.456 ± 0.165). Synergism was observed in most combinations indicating the potential use of S. longipedunculata in combination with artemether and lumefantrine in combating resistance.

Keywords: Securidaca longipedunculata; combination; malaria; plasmodium falciparum; synergism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Scatter plots of drugs-extracts combinations against W2 strain of *P. falciparum*.

**Figure 2**
Scatter plots of drugs-extracts combinations against DD2 strain of *P. falciparum*.

**Figure 3**
Scatter plots of drug-extract combinations against D6 strain of *P. falciparum*.

**Figure 4**
Scatter plots of drugs-extracts combinations against field isolates ex vivo of *P. falciparum*.

**Figure 5**
Scatter plots of control drugs combinations.

See this image and copyright information in PMC

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[1] World Health Organization (WHO) Malaria Report. WHO; Geneva, Switzerland: 2020.

[2] World Health Organization (WHO) Malaria Report. WHO; Geneva, Switzerland: 2020.

[3] Zaw M.T., Emran N.A., Lin Z. Updates on k13 mutant alleles for artemisinin resistance in Plasmodium falciparum. J. Microbiol. Immunol. Infect. 2018;51:159–165. doi: 10.1016/j.jmii.2017.06.009. - DOI - PubMed

[4] Zaw M.T., Emran N.A., Lin Z. Updates on k13 mutant alleles for artemisinin resistance in Plasmodium falciparum. J. Microbiol. Immunol. Infect. 2018;51:159–165. doi: 10.1016/j.jmii.2017.06.009. - DOI - PubMed

[5] Menard D., Dondorp A. Antimalarial drug resistance: A threat to malaria elimination. Cold Spring Harb. Perspect. Med. 2017;7:a025619. doi: 10.1101/cshperspect.a025619. - DOI - PMC - PubMed

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[7] Saifi M.A., Beg T., Harrath A.H., Altayalan F.S.H., Qurais S.A. Antimalarial drugs: Mode of action and status of resistance. Afr. J. Pharm. Pharmacol. 2013;7:148–156. doi: 10.5897/AJPPX12.015. - DOI

[8] Saifi M.A., Beg T., Harrath A.H., Altayalan F.S.H., Qurais S.A. Antimalarial drugs: Mode of action and status of resistance. Afr. J. Pharm. Pharmacol. 2013;7:148–156. doi: 10.5897/AJPPX12.015. - DOI

[9] Tse E.G., Korsik M., Todd M.H. The past, present and future of anti-malarial medicines. Malar. J. 2019;18:93. doi: 10.1186/s12936-019-2724-z. - DOI - PMC - PubMed

[10] Tse E.G., Korsik M., Todd M.H. The past, present and future of anti-malarial medicines. Malar. J. 2019;18:93. doi: 10.1186/s12936-019-2724-z. - DOI - PMC - PubMed

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Synergism in Antiplasmodial Activities of Artemether and Lumefantrine in Combination with Securidaca longipedunculata Fresen (Polygalaceae)

Affiliations

Synergism in Antiplasmodial Activities of Artemether and Lumefantrine in Combination with Securidaca longipedunculata Fresen (Polygalaceae)

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

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References

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