Efforts have been intensified to search for more effective antimalarial agents because of the observed failure of some artemisinin-based combination therapy (ACT) treatments of malaria in Ghana. Xylopic acid, a pure compound isolated from the fruits of the Xylopia aethiopica, was investigated to establish its attributable prophylactic, curative antimalarial, and antipyretic properties. The antimalarial properties were determined by employing xylopic acid (10–100？mg/kg) in ICR mice infected with Plasmodium berghei. Xylopic acid exerted significant ( ) effects on P. berghei infection similar to artemether/lumefantrine, the standard drug. Furthermore, it significantly ( ) reduced the lipopolysaccharide- (LPS-) induced fever in Sprague-Dawley rats similar to prednisolone. Xylopic acid therefore possesses prophylactic and curative antimalarial as well as antipyretic properties which makes it an ideal antimalarial agent. 1. Introduction Malaria, caused by Plasmodium parasite, is a leading poverty-associated disease that undermines the development of countries. The numbers of disease cases and deaths was 225 million and 781？000 respectively in 2009 [1]. Children under five years and pregnant women (vulnerable groups) succumb to the devastating effects of the disease making the disease a major global infectious disease. Chemotherapy has ultimately been the central tool for management of malaria, and combination of drug regimens has become the practice of choice because of their increased therapeutic efficacy over monotherapy and other benefits which include decreased cytotoxicity and delay or prevention of the development of drug resistance [2]. Plasmodium falciparum (Pf), the most lethal malaria pathogen, has developed resistance to some antimalarials [3]. This makes it imperative to search for newer, more effective antimalarial agents. Plants have served as reliable sources of drugs especially antimalarials [4]. The fruits of Xylopia aethiopica are used traditionally for the treatment of malaria but the active principle(s) responsible for the observed antimalarial effect of the extract is still not known [5, 6]. Xylopic acid, a kaurene diterpene, occurs as the major constituent in the fruits of Xylopia aethiopica and is reported to possess analgesic properties [7]. Xylopic acid, unlike kaurenoic acid, has no cytotoxic effect against human cancer cells [8], making the compound a safe one for the treatment of diseases where selective toxicity towards the parasite is highly needed. In the light of the above, xylopic acid was evaluated for its antimalarial and
References
[1]
WHO, World Malaria Report, World Health Organization, Geneva, Switzerland, 2010.
[2]
K. Mishra, A. P. Dash, B. K. Swain, and N. Dey, “Anti-malarial activities of Andrographis paniculata and Hedyotis corymbosa extracts and their combination with curcumin,” Malaria Journal, vol. 8, no. 1, article 26, 2009.
[3]
M. Randrianarivelojosia, V. T. Rasidimanana, H. Rabarison et al., “Plants traditionally prescribed to treat tazo (malaria) in the eastern region of Madagascar,” Malaria Journal, vol. 2, no. 1, p. 25, 2003.
[4]
L. K. Basco, S. Mitaku, A.-L. Skaltsounis et al., “In vitro activities of furoquinoline and acridone alkaloids against Plasmodium falciparum,” Antimicrobial Agents and Chemotherapy, vol. 38, no. 5, pp. 1169–1171, 1994.
[5]
M. M. Suleiman, M. Mamman, Y. O. Aliu, and J. O. Ajanusi, “Anthelmintic activity of the crude methanol extract of Xylopia aethiopica against Nippostrongylus brasiliensis in rats,” Veterinarski Arhiv, vol. 75, no. 6, pp. 487–495, 2005.
[6]
L. N. Tatsadjieu, J. J. Essia Ngang, M. B. Ngassoum, and F.-X. Etoa, “Antibacterial and antifungal activity of Xylopia aethiopica, Monodora myristica, Zanthoxylum xanthoxyloides and Zanthoxylum leprieurii from Cameroon,” Fitoterapia, vol. 74, no. 5, pp. 469–472, 2003.
[7]
E. Woode, E. O. Ameyaw, E. Boakye-Gyasi, and W. K. M. Abotsi, “Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal) A. Rich, (Annonaceae) and the major constituent, xylopic acid in murine models,” Journal of Pharmacy and BioAllied Sciences, vol. 4, no. 4, pp. 291–301, 2012.
[8]
B. C. Cavalcanti, D. P. Bezerra, H. I. F. Magalh？es et al., “Kauren-19-oic acid induces DNA damage followed by apoptosis in human leukemia cells,” Journal of Applied Toxicology, vol. 29, no. 7, pp. 560–568, 2009.
[9]
National Institute of Health Guidelines for the Care and Use of Laboratory Animals and National Institutes of Health, Office of Science and Health Reports, Guide for care and use of laboratory animals 83-23, Office of Science and Health Reports, Department of Health and Human Services, Bethesda, Md, USA, 1996.
[10]
A. Ishih, T. Suzuki, T. Hasegawa, S. Kachi, H. Wang, and M. Terada, “In vivo evaluation of combination effects of chloroquine with cepharanthin or minocycline hydrochloride against blood-induced choloquine-resistant Plasmodium berghei NK65 infections,” Tropical Medicine and Health, vol. 32, pp. 15–19, 2004.
[11]
A. H. Al-Adhroey, Z. M. Nor, H. M. Al-Mekhlafi, and R. Mahmud, “Ethnobotanical study on some Malaysian anti-malarial plants: a community based survey,” Journal of Ethnopharmacology, vol. 132, no. 1, pp. 362–364, 2010.
[12]
W. Peters, “Drug resistance in Plasmodium berghei Vincke and Lips, 1948. III. Multiple drug resistance,” Experimental Parasitology, vol. 17, no. 1, pp. 97–102, 1965.
[13]
F. A. Santos and V. S. N. Rao, “A study of the anti-pyretic effect of quinine, an alkaloid effective against cerebral malaria, on fever induced by bacterial endotoxin and yeast in rats,” Journal of Pharmacy and Pharmacology, vol. 50, no. 2, pp. 225–229, 1998.
[14]
N. Depinay, J. F. Franetich, A. C. Grüner et al., “Inhibitory effect of TNF-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations,” PLoS One, vol. 6, no. 3, Article ID e17464, 2011.
[15]
D. S. Hansen, “Inflammatory responses associated with the induction of cerebral malaria: lessons from experimental murine models,” PLoS Pathogens, vol. 8, no. 2, Article ID e1003045, 2012.
[16]
J. Golenser, J. H. Waknine, M. Krugliak, N. H. Hunt, and G. E. Grau, “Current perspectives on the mechanism of action of artemisinins,” International Journal for Parasitology, vol. 36, no. 14, pp. 1427–1441, 2006.
[17]
P. I. German and F. T. Aweeka, “Clinical pharmacology of artemisinin-based combination therapies,” Clinical Pharmacokinetics, vol. 47, no. 2, pp. 91–102, 2008.
[18]
G. Kokwaro, L. Mwai, and A. Nzila, “Artemether/lumefantrine in the treatment of uncomplicated falciparum malaria,” Expert Opinion on Pharmacotherapy, vol. 8, no. 1, pp. 75–94, 2007.
[19]
A. Haque, S. E. Best, F. H. Amante et al., “High parasite burdens cause liver damage in mice following Plasmodium berghei ANKA infection independently of CD8+ T cell-mediated immune pathology,” Infection and Immunity, vol. 79, no. 5, pp. 1882–1888, 2011.
[20]
I. Petersen, R. Eastman, and M. Lanzer, “Drug-resistant malaria: molecular mechanisms and implications for public health,” FEBS Letters, vol. 585, no. 11, pp. 1551–1562, 2011.
[21]
D. R. Hill, J. K. Baird, M. E. Parise, L. S. Lewis, E. T. Ryan, and A. J. Magill, “Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I,” The American Journal of Tropical Medicine and Hygiene, vol. 75, no. 3, pp. 402–415, 2006.
[22]
G. S. Dow, A. J. Magill, and C. Ohrt, “Clinical development of new prophylactic antimalarial drugs after the 5th Amendment to the Declaration of Helsinki,” Therapeutics and Clinical Risk Management, vol. 4, no. 4, pp. 803–819, 2008.
[23]
J. F. Ryley and W. Peters, “The antimalarial activity of some quinolone esters,” Annals of Tropical Medicine and Parasitology, vol. 64, no. 2, pp. 209–222, 1970.
