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Licensed Unlicensed Requires Authentication Published by De Gruyter November 7, 2013

Analgesic, anti-inflammatory, and heme biomineralization inhibitory properties of Entada africana ethanol leaf extract with antiplasmodial activity against Plasmodium falciparum

Ifeoma C. Ezenyi, Lalasoanirina Ranarivelo, Salawu A. Oluwakanyinsola and Martins Emeje


Background:Entada africana (EA) is a medicinal plant used in West Africa for the treatment of malaria fever, but its efficacy against malaria is yet to be scientifically validated. Our study explores the antimalarial potential of the ethanol leaf extract of EA.

Methods: The antiplasmodial activity of EA against chloroquine-sensitive (HB3) and chloroquine-resistant (FcM29) Plasmodium falciparum was determined as well as its peripheral antinociceptive and anti-inflammatory properties. The effect of the extract on human monocytic (THP-1) cells was recorded as a measure of cytotoxicity, whereas the inhibitory effect on heme detoxification was evaluated as a possible mechanism of antiplasmodial activity.

Results: At a concentration of 100 μg/mL, EA was noncytotoxic and displayed moderate antiplasmodial activity against HB3 and FcM29 (IC50=26.36 and 28.86 μg/mL, respectively). It also exhibited concentration-dependent inhibition of synthetic heme (IC50=16 mg/mL). The extract (200 mg/kg body weight) showed significant (p<0.05) inhibition of paw inflammation, and significantly (p<0.01, 0.05) reduced the number of abdominal writhes induced by acetic acid (58.62%–65.51%), which was higher compared to that of diclofenac (50%, p<0.05).

Conclusions: These findings suggest that peripheral antinociceptive effects and parasiticidal activity of EA contribute to its antimalarial properties and it can be further explored as effective therapy against malaria infection.

Corresponding author: Ifeoma C. Ezenyi, Department of Pharmacology and Toxicology, National Institute for Pharmaceutical Research and Development, P.M.B. 21, Abuja, 900001 Nigeria, Phone: +234-803-6225293, E-mail:


The authors acknowledge Mr. Sam Okhale for his assistance in HPLC fingerprinting. I.C. Ezenyi is grateful to Dr. Dhiman Sarkar of the National Chemical Laboratory, Pune, India, where the cytotoxicity assay was conducted.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.


1. Roll Back Malaria. Key malaria facts, 2012. Available at: Accessed: 3 May 2013.Search in Google Scholar

2. World Health Organization Malaria fact sheet No. 94, 2010. Available at: Accessed 1 Apr 2013.Search in Google Scholar

3. Ridley RG. Medical need, scientific opportunity and the drive for antimalarial drugs. Nature 2002;415:686–93.10.1038/415686aSearch in Google Scholar

4. Wangchuk P, Keller PA, Pyne SG, Taweechotipatr M, Tonsomboon A, Rattanajak R, et al. Evaluation of an ethnopharmacologically selected Bhutanese medicinal plants for their major classes of phytochemicals and biological activities. J Ethnopharmacol 2011;137:730–42.10.1016/j.jep.2011.06.032Search in Google Scholar

5. Diallo D, Paulsen BS, Liljebäck TH, Michaelsen TE. Polysaccharides from the roots of Entada africana Guill. et Perr., Mimosaceae, with complement fixing activity. J Ethnopharmacol 2001;74:159–71.10.1016/S0378-8741(00)00361-5Search in Google Scholar

6. Ahua KM, Ioset JR, Ioset KN, Diallo D, Mauël J, Hostettmann K. Antileishmanial activities associated with plants used in the Malian traditional medicine. J Ethnopharmacol 2007;110: 99–104.10.1016/j.jep.2006.09.030Search in Google Scholar

7. Karou SD, Tchacondo T, Ouattara L, Anani K, Savadogo A, Agbonon A, et al. Antimicrobial, antiplasmodial, haemolytic and antioxidant activities of crude extracts from three selected Togolese medicinal plants. Asian Pac J Trop Med 2011;4:808–13.10.1016/S1995-7645(11)60199-5Search in Google Scholar

8. Cioffi G, Dal Piaz F, De Caprariis P, Sanogo R, Marzocco S, Autore G, et al. Antiproliferative triterpene saponins from Entada africana. J Nat Prod 2006;69:1323–9.10.1021/np060257wSearch in Google Scholar

9. Obidike IC, Emeje MO. Microencapsulation enhances the antiulcerogenic properties of Entada africana leaf extract. J Ethnopharmacol 2011;137:553–61.10.1016/j.jep.2011.06.012Search in Google Scholar

10. National Institutes of Health. Guide for the care and use of laboratory animals. NIH Publ. No. 86-23, Revised. Bethesda, MD: NIH, 1985.Search in Google Scholar

11. Trager W, Jensen JB. Human malaria parasites in continuous culture. Science 1976;193:673–5.10.1126/science.781840Search in Google Scholar

12. Bennett TN, Paguio M, Gligorijevic B, Seudieu C, Kosar AD, Davidson E, et al. Novel, rapid, and inexpensive cell-based quantification of antimalarial drug efficacy. Antimicrob Agents Chemother 2004;48:1807–10.10.1128/AAC.48.5.1807-1810.2004Search in Google Scholar

13. Deharo E, García RN, Oporto P, Gimenez A, Sauvain M, Jullian V, et al. A non-radiolabelled ferriprotoporphyrin IX biomineralisation inhibition test for the high throughput screening of antimalarial compounds. Exp Parasitol 2002;100:252–6.10.1016/S0014-4894(02)00027-9Search in Google Scholar

14. Ekpendu TO, Akah PA, Adesomoju AA, Okogun JI. Antiinflamatory and antimicrobial activities of Mitracarpus scaber extracts. Int J Pharmacognosy 1994;32:191–6.10.3109/13880209409082992Search in Google Scholar

15. Vongtau HO, Abbah J, Mosugu O, Chindo BA, Ngazal IE, Salawu AO, et al. Antinociceptive profile of the methanolic extract of Neorautanenia mitis root in rats and mice. J Ethnopharmacol 2004;92:317–24.10.1016/j.jep.2004.03.014Search in Google Scholar

16. Onyeibor O, Croft SL, Dodson HI, Feiz-Haddad M, Kendrick H, Millington NJ, et al. Synthesis of some cryptolepine analogues, assessment of their antimalarial and cytotoxic activities, and consideration of their antimalarial mode of action. J Med Chem 2005;48:2701–9.10.1021/jm040893wSearch in Google Scholar

17. Tibiri A, Rakotonandrasana O, Nacoulma GO, Banzouzi JT. Radical scavenging activity, phenolic content and cytotoxicity of bark and leaves extract of Entada africana Guill. and Perr. (Mimosaceae). J Biol Sci 2007;7:959–63.10.3923/jbs.2007.959.963Search in Google Scholar

18. Leed A, DuBay K, Ursos LM, Sears D, De Dios AC, Roepe PD. Solution structures of antimalarial drug-heme complexes. Biochemistry 2002;41:10245–55.10.1021/bi020195iSearch in Google Scholar

19. Garavito G, Rincon J, Arteaga L, Hata Y, Bourdy G, Gimenez A, et al. Antimalarial activity of some Colombian medicinal plants. J Ethnopharmacol 2006;107:460–62.10.1016/j.jep.2006.03.033Search in Google Scholar

20. Ruiz L, Ruiz L, Maco M, Cobos M, Gutierrez-Choquevilca A-L, Roumy V. Plants used by native Amazonian groups from the Nanay river (Peru) for the treatment of malaria. J Ethnopharmacol 2011;133:917–21.10.1016/j.jep.2010.10.039Search in Google Scholar

21. Dell’Agli M, Parapini S, Basilico N, Verotta L, Taramelli D, Berry C, et al. In vitro studies on the mechanism of action of two compounds with antiplasmodial activity: ellagic acid and 3,4,5-trimethoxyphenyl- (6′-O-galloyl)-β-d-glucopyranoside. Planta Med 2003;69:162–4.10.1055/s-2003-37706Search in Google Scholar

22. Ignatushchenko MV, Winter RW, Bachinger HP, Hinrichs DJ, Riscoe MK. Xanthones as antimalarial agents: studies of a possible mode of action. FEBS Lett 1997;409:67–73.10.1016/S0014-5793(97)00405-5Search in Google Scholar

23. Lehane AM, Hayward R, Saliba KJ, Kirk K. A verapamil-sensitive chloroquine-associated H+ leak from the digestive vacuole in chloroquine-resistant malaria parasites. J Cell Sci 2008;121:1624–32.10.1242/jcs.016758Search in Google Scholar PubMed

24. Menting J, Tilley L, Deady L, Ng K, Simpson R, Cowman AF, et al. The antimalarial drug, chloroquine, interacts with lactate dehydrogenase from Plasmodium falciparum. Mol Biochem Parasitol 1997;88:215–24.10.1016/S0166-6851(97)00095-9Search in Google Scholar

25. Aguiar AC, Santos Rde M, Figueiredo FJ, Cortopassi WA, Pimentel AS, França TC, et al. Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites. PLoS One 2012;7:e37259.10.1371/journal.pone.0037259Search in Google Scholar

26. Hanum PS, Hayano M, Kojima S. Cytokine and chemokine responses in a cerebral malaria-susceptible or -resistant strain of mice to Plasmodium berghei ANKA infection: early chemokine expression in the brain. Int Immunol 2003;15:633–40.10.1093/intimm/dxg065Search in Google Scholar

27. Malaguarnera L, Musumeci S. The immune response to Plasmodium falciparum malaria. Lancet Infect Dis 2002;2:472–8.10.1016/S1473-3099(02)00344-4Search in Google Scholar

28. Morris CJ. Carrageenan-induced paw edema in the rat and mouse. Methods Mol Biol 2003;225:115–21.10.1385/1-59259-374-7:115Search in Google Scholar

29. Bueno L, Fioramonti J. Visceral perception: inflammatory and non-inflammatory mediators. Gut 2002;5:i19–23.10.1136/gut.51.suppl_1.i19Search in Google Scholar PubMed PubMed Central

30. Bighetti EJ, Hiruma-Lima CA, Gracioso JS, Souza Brito AR. Anti-inflammatory and antinociceptive effects in rodents of the essential oil of Croton cajucara Benth. J Pharm Pharmacol 1999;51:1447–53.10.1211/0022357991777100Search in Google Scholar PubMed

31. Schofield L, Hackett F. Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites. J Exp Med 1993;177:145–53.10.1084/jem.177.1.145Search in Google Scholar PubMed PubMed Central

32. Arese P, Schwarzer E. Malarial pigment (hemozoin): a very active ‘inert’ substance. Ann Trop Med Parasitol 1997;91:501–16.10.1080/00034983.1997.11813168Search in Google Scholar

33. Jaramillo M, Gowda DC, Radzioch D, Olivier M. Hemozoin increases IFN-α-inducible macrophage nitric oxide generation through ERK- and NF-κB-dependent pathways. J Immunol 2003;171:4243–53.10.4049/jimmunol.171.8.4243Search in Google Scholar PubMed

Received: 2013-5-18
Accepted: 2013-10-3
Published Online: 2013-11-7
Published in Print: 2014-5-1

©2014 by Walter de Gruyter Berlin/Boston

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