Antimalarial Activities of a Therapeutic Combination of Azadirachta Indica, Mangifera Indica and Morinda Lucida Leaves: A Molecular View of Its Activity on Plasmodium Falciparum Proteins

Overview

Journal Acta Parasitol

Specialty Parasitology

Date 2023 Jul 20

PMID 37474844

Authors

Suliat Iyabode Abdulai

Ahmed Adebayo Ishola

Clement Olatunbosun Bewaji

Affiliations

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Abstract

Background: The search for new antimalarial drugs remains elusive prompting research into antimalarial combinations from medicinal plants due to their cheapness, efficacy and availability. Azadirachta indica (AI), Morinda lucida (ML) and Mangifera indica (MI) have all been reported as potent antimalarial plants.

Purpose: This study evaluated the efficacy of an antimalarial combination therapeutics prepared from leaves of AI, ML and MI using in vitro, in vivo and molecular methods.

Methods: Refined extracts of the plants combination was made by partitioning the aqueous extract of plants combinations (AI + MI, AI + ML, MI + ML, AI + MI + ML) using methanol and ethyl acetate consecutively. The resulting ethyl acetate partitioned fraction was evaluated for its antimalarial activity. Molecular docking and molecular dynamics simulation were employed to determine the possible mechanism of action of the constituent of the most active combination against four important P. falciparum proteins.

Results: The result revealed that the refined extract from combinations AI + ML and MI + ML at 16 mg/kg bodyweight have the highest chemo-suppressive effect of 90.7% and 91.0% respectively compared to chloroquine's 100% at 10 mg/kg. Also, refined extract from MI + ML combination improved PCV levels significantly (p < 0.05) compared to controls. Molecular docking revealed oleanolic acid and ursolic acid as multiple inhibitors of plasmepsin II, hiso-aspartic protease, falcipain-2 and P. falciparum Eonyl acyl-carrier protein reductase with relative stability during 100 ns of simulation.

Conclusion: The study unveiled the potentials of ML and MI as good candidates for antimalarial combination therapy and further established their use together as revealed in folklore medicine.

Citing Articles

Potentials of Terpenoids as Inhibitors of Multiple Plasmodium falciparum Protein Drug Targets.

Ishola A, Adewole K, Adebayo J, Balogun E Acta Parasitol. 2023; 68(4):793-806.

PMID: 37603126 DOI: 10.1007/s11686-023-00711-z.

References

Dondorp A, Nosten F, Yi P, Das D, Phyo A, Tarning J . Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009; 361(5):455-67. PMC: 3495232. DOI: 10.1056/NEJMoa0808859. View

Majori G . [Combined antimalarial therapy using artemisinin]. Parassitologia. 2004; 46(1-2):85-7. View

Nwaka S, Ramirez B, Brun R, Maes L, Douglas F, Ridley R . Advancing drug innovation for neglected diseases-criteria for lead progression. PLoS Negl Trop Dis. 2009; 3(8):e440. PMC: 2727960. DOI: 10.1371/journal.pntd.0000440. View

DiMasi J, Hansen R, Grabowski H . The price of innovation: new estimates of drug development costs. J Health Econ. 2003; 22(2):151-85. DOI: 10.1016/S0167-6296(02)00126-1. View

Willcox M, Bodeker G . Traditional herbal medicines for malaria. BMJ. 2004; 329(7475):1156-9. PMC: 527695. DOI: 10.1136/bmj.329.7475.1156. View

Patwardhan B, Mashelkar R . Traditional medicine-inspired approaches to drug discovery: can Ayurveda show the way forward?. Drug Discov Today. 2009; 14(15-16):804-11. DOI: 10.1016/j.drudis.2009.05.009. View

McDonald M, Rosbash M . Microarray analysis and organization of circadian gene expression in Drosophila. Cell. 2001; 107(5):567-78. DOI: 10.1016/s0092-8674(01)00545-1. View

Peters W . Drug resistance in Plasmodium berghei Vincke and Lips, 1948. I. Chloroquine resistance. Exp Parasitol. 1965; 17(1):80-9. DOI: 10.1016/0014-4894(65)90012-3. View

Carvalho L, Brandao M, Lopes J, Krettli A . Antimalarial activity of crude extracts from Brazilian plants studied in vivo in Plasmodium berghei-infected mice and in vitro against Plasmodium falciparum in culture. Braz J Med Biol Res. 1991; 24(11):1113-23. View

10.

OBoyle N, Banck M, James C, Morley C, Vandermeersch T, Hutchison G . Open Babel: An open chemical toolbox. J Cheminform. 2011; 3:33. PMC: 3198950. DOI: 10.1186/1758-2946-3-33. View

11.

Trott O, Olson A . AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2009; 31(2):455-61. PMC: 3041641. DOI: 10.1002/jcc.21334. View

12.

Kumari R, Kumar R, Lynn A . g_mmpbsa--a GROMACS tool for high-throughput MM-PBSA calculations. J Chem Inf Model. 2014; 54(7):1951-62. DOI: 10.1021/ci500020m. View

13.

Aldulaimi O, Uche F, Hameed H, Mbye H, Ullah I, Drijfhout F . A characterization of the antimalarial activity of the bark of Cylicodiscus gabunensis Harms. J Ethnopharmacol. 2017; 198:221-225. DOI: 10.1016/j.jep.2017.01.014. View

14.

Soh P, Witkowski B, Olagnier D, Nicolau M, Garcia-Alvarez M, Berry A . In vitro and in vivo properties of ellagic acid in malaria treatment. Antimicrob Agents Chemother. 2008; 53(3):1100-6. PMC: 2650562. DOI: 10.1128/AAC.01175-08. View

15.

Masibo M, He Q . Major Mango Polyphenols and Their Potential Significance to Human Health. Compr Rev Food Sci Food Saf. 2021; 7(4):309-319. DOI: 10.1111/j.1541-4337.2008.00047.x. View

16.

Phillipson J, Wright C . Medicinal plants in tropical medicine. 1. Medicinal plants against protozoal diseases. Trans R Soc Trop Med Hyg. 1991; 85(1):18-21. DOI: 10.1016/0035-9203(91)90139-p. View

17.

Francis S, Gluzman I, Oksman A, Knickerbocker A, Mueller R, Bryant M . Molecular characterization and inhibition of a Plasmodium falciparum aspartic hemoglobinase. EMBO J. 1994; 13(2):306-17. PMC: 394809. DOI: 10.1002/j.1460-2075.1994.tb06263.x. View

18.

Ghoshal S, Prasad B, Lakshmi V . Antiamoebic activity of Piper longum fruits against Entamoeba histolytica in vitro and in vivo. J Ethnopharmacol. 1996; 50(3):167-70. DOI: 10.1016/0378-8741(96)01382-7. View

19.

Asase A, Akwetey G, Achel D . Ethnopharmacological use of herbal remedies for the treatment of malaria in the Dangme West District of Ghana. J Ethnopharmacol. 2010; 129(3):367-76. DOI: 10.1016/j.jep.2010.04.001. View

20.

Simelane M, Shonhai A, Shode F, Smith P, Singh M, Opoku A . Anti-plasmodial activity of some Zulu medicinal plants and of some triterpenes isolated from them. Molecules. 2013; 18(10):12313-23. PMC: 6269946. DOI: 10.3390/molecules181012313. View