Research Article | OPEN ACCESS
Investigation of Traditional Palestinian Medicinal Plant Inula viscose as Potential Anti-malarial Agent
1M. Akkawi, 1I. Abbasi, 1S. Jaber, 1Q. Aburemeleh, 2A. Naseredin and 3Pierre Lutgen
1Department of Life Sciences, College of Science and Technology
2Nutrition and Health Research Institute, Faculty of Medicine, Al-Quds University, West Bank, Palestine
3IFBV-BELHERB, Luxembourg
British Journal of Pharmacology and Toxicology 2014 5:153-159
Received: January 27, 2014 | Accepted: February 10, 2014 | Published: October 20, 2014
Abstract
Malaria is a life threatening parasitic disease which is prevalent mainly in developing countries; it is the main cause of global mortality and morbidity. Development and search of novel and effective anti-malarial agents to overcome chloroquine resistance have become a very important issue. Most anti-malarial drugs target the erythrocytic stage of malaria infection, where hemozoin synthesis takes place and is considered a crucial process for the parasite survival. Throughout last decades, natural products have been a significant source of chemotherapeutics especially against malaria. Inula viscose, is a shrub that grows around the Mediterranean basin and considered as an important Palestinian traditional medicinal herb. In this research it was found that the Palestinian flora Inula viscose alcoholic extract has a significant and promising anti-malarial effect in both in vitro and in vivo systems. The crude alcoholic extract of Inula viscose has the capability to impede the formation of &beta-hematin in-vitro; with an efficiency of about 93% when compared to the standard chloroquine which gave 94% at comparable concentrations. In vivo studies showed that this crude extract inhibited the growth of Plasmodium parasites in the red blood cells at a rate of about 96.6%, with an EC50 value of 0.55 ng/mL. Several secondary plant metabolites may be responsible for this anti-malarial activity; the effect also may be most probably due to the presence of high concentrations of nerolidol which has often been found at high concentrationsin this plant. Nerolidol shows a stronger inhibition of hypoxanthine incorporation than quinine. Its anti-malarial effect is potentiated by other essential oils. Nerolidol is also found in several Artemisia species and in Cymbopogon citrates (lemongrass) and Virola surinamensis, all plants known for their anti-malarial properties.
Keywords:
&beta-hematin, anti-malarial drug resistance, anti-malarial drugs, chloroquine, ferriprotoporphyrin (IX), hemozoin, Inula viscose,
References
-
Abu Zarga, M.H., E.M. Hamed, S.S. Sabri, W. Voelter and Z. Klaus-Peter, 1998. New sesquiterpenoids from the Jordanian medicinal plant Inula viscosa. J. Nat. Prod., 61: 798-800.
CrossRef PMid:9644068 -
Akkawi, M., A. Aljazzar, M. Abul Haj and Q. Abu- Remeleh, 2012a. The effect of Cis-2-(1H-imidazole- 2-yl)-1H-imidazole dichloro platinum (II) on the in-vitro formation of ß-Hematin. Brit. J. Pharmacol. Toxicol., 3(2): 65-69.
-
Akkawi, M., A.K. Sharif, K. Salem, A. Saleh and Q. AbuRemeleh, 2012b. Wild sage (Salvia officinalis) as a potential anti-malarial drug. Malaria J., 11(Suppl. 1): 3.
CrossRef PMCid:PMC3472673 -
Bannister, L.H. and I.W. Sherman, 2009. Plasmodium. Encyclopedia of Life Sciences (ELS). John Wiley and Sons Ltd., Chichester.
-
Blauer, G. and M. Akkawi, 1997. Investigations of B- and ß-hematin. J. Inorg. Biochem., 66: 145-152.
CrossRef -
Blauer, G. and M. Akkawi, 2000. On the preparation of ß-Hematin. Biochem. J., 346: 249-250.
CrossRef PMid:10677340 PMCid:PMC1220847 -
Bohlmann, F., P.K. Mahanta, J. Jakupovic, R.C. Rastogi and A.A. Natu, 1978. New sesquiterpene lactones from inula species. Phytochemistry, 17(7): 1165-1172.
CrossRef -
Bowden, M.E., M.B. Grow and T. Sullivan, 2003. Pharmaceutical achievers: The human face for pharmacuitical research. 2-4 USA. Retrieved from: www.amazon.com › ... › Professionals & Academics › Scientists?.
-
Danino, O., H.E. Gottlieb, S. Grossman and M. Bergman, 2009. Antioxidant activity of 1,3-dicaffeoylquinic acid isolated from Inula viscosa. Food Res. Int., 42: 1273-1280.
CrossRef -
Deharo, E., R. Garcia, P. Oporto, A. Gimenez, M. Sauvian, V. Jullian and H. Ginsburg, 2002. A non-radiolabelled ferriprotoporphyrin IX biomineralisation inhibition test for the high throughput screening of anti-malarial compounds. Exp. Parasitol., 100: 252-256.
CrossRef -
Dondorp, A., F. Nosten, P. Yi, D. Das, A. Phae Phyo, J. Tarning, K. Lwin, F. Ariey, W. Hanpithakpong, W. Lee, P. Ringwald, K. Silamut, M. Imwong, K. Chotivanich, P. Lim, T. Herdman, S. Sam An, S. Yeung, P. Singhasivanon, N. Day, N. Lindegardh, D. Socheat and N. White, 2009. Artemisinin resistance in Plasmodium falciparum malaria. New Engl. J. Med., 361: 455-467.
CrossRef PMid:19641202 PMCid:PMC3495232 -
Egan, T.J., J.M. Combrinck, J. Egan, G.R. Hearne, H.M. Marques, S.N. Tenteni, B.T. Sewells, P.J. Smith, D. Taylor, D.A. Vanschalkwyk and J.C. Walden, 2002. Fate of haem iron in the malaria parasite Plasmodium falciparum. Biochem. J., 365: 343-347.
CrossRef PMid:12033986 PMCid:PMC1222701 -
Fontana, G., S. La Rocca, S. Passannanti and M.P. Paternostro, 2007. Sesquiterpene compounds from Inula viscosa. Nat. Prod. Res., 21(9): 824-7.
CrossRef PMid:17654288 -
Goldberg, D., A. Slater, A. Cerami and G. Henderson, 1990. Hemoglobin degradation in the malaria parasite Plasmodium falciparum: An ordered process in a unique organelle. P. Natl. Acad. Sci. USA, 87: 931-935.
CrossRef -
Grande, M., F. Piera, A. Cuenca, P. Torres and I.S. Bellido,1985. Flavonoids from Inula viscosa. Planta Med., 51(5): 414-419.
CrossRef PMid:17342599 -
Hawley, S.R., P.G. Bray, M. Munthin, J.D. Atkinson, P.M. O'neill and S.A. Ward, 1998. Relationship between anti-malarial drug activity, accumulation and inhibition of heme polymerization in Plasmodium falciparum in Vitro. Antimicrob. Agents Ch., 42(3): 682-686.
-
Jaber, S., S. Abu-Lafi, A. Asharif, M. Qutob, Q. Aburemeleh and M. Akkawi, 2013. Potential anti-malarial activity from alcoholic extracts of wild Salvia palaestina leaves. Brit. J. Pharm. Toxicol., 4(5): 201-206.
-
Kanan, G.J. and R.A. Al-Najar, 2008. In vitro antifungal activities of various plant crude extracts and fractions against citrus post-harvest disease agent Penicillium digitatum. Jordan J. Biol. Sci., 1: 89-99.
-
Kenmogne, M., E. Prost, D. Harakat, M.J. Jacquier, M. Frederich, L.B. Sondengam, M. Zeches and P. Waffo-Teguo, 2006. Five labdane diterpenoids from the seeds of Aframomum zambesiacum. Phytochemistry, 67(5): 433-8.
CrossRef PMid:16321410 -
Klemba, M., W. Beatty, I. Gluzman and D. Goldberg, 2004. Trafficking of plasmepsin II to the food vacuole of the malaria parasite Plasmodium falciparum. J. Cell Biol., 164: 47-56.
CrossRef PMid:14709539 PMCid:PMC2171955 -
Klones, N., O. Tan, K. Jackson, D. Goldberg, M. Klemba and L. Tille, 2007. Evaluation of pH during cytostomal endocytosis and vacuolar catabolism of haemoglobin in Plasmodium falciparum. Biochem. J., 407: 343-354.
CrossRef PMid:17696875 PMCid:PMC2275073 -
Liu, J., I. Gluzman, M.E. Drew and D.E. Goldberg, 2005. The role of Plasmodium falciparum food vacuole plasmepsins. J. Biol. Chem., 280: 1432-1437.
CrossRef PMid:15513918 -
Má-ez, S., M.C. Recio, I. Gil, C. Gómez, R.M. Giner, P.G. Waterman and J.L. Ríos, 1999. A glycosyl analogue of diacylglycerol and other anti-inflammatory constituents from Inula viscosa. J. Nat. Prod., 62(4): 601-604.
CrossRef PMid:10217718 -
Orjih, A.U. and C.D. Fitch, 1993. Hemozoin production by Plasmodium falciparum: Variation with strain and exposure to chloroquine. Biochim. Biophys. Acta, 1157: 270-274.
CrossRef -
Pagola, S., P.W. Stephens, D.S. Bohle, A.D. Kosar and S.K. Madsen, 2000. The structure of malaria pigment ß-Haematin. Nature, 404: 307-310.
CrossRef PMid:10749217 -
Salazar, E., E.M. Bank, N. Ramsey, K.C. Hess, K.W. Deitsch, L.R. Levin and J. Buck, 2012. Characterization of padenylyl cyclase-beta and its role in erythrocytic stage parasites. PLoS One, 7: e39769.
CrossRef PMid:22761895 PMCid:PMC3383692 -
Saxona, S., N. Pant, D.C. Jain and R.S. Bhakuni, 2003. Anti-malarial agents from plant sources. Curr. Sci. India, 85(9): 1314-1330.
-
Scalbert, A., I.T. Johnson and M. Saltmarsh, 2005. Polyphenols: Antioxidants and beyond. Am. J. Clin. Nutr., 81: 215S-217S.
CrossRef PMid:15640483 -
Schinella, G.R., H.A. Tournier, J.M. Prieto, P. Mordujovich de Buschiazzo and J.L. Ríos, 2002. Antioxidant activity of anti-inflammatory plant extracts. Life Sci., 70: 1023-1033.
CrossRef -
Seatlholo, S.T., 2007. The biological activity of essential oil constituents. Thesis, University of Witwatersrand, Johannesburg.
-
Shohaib, T., M. Shafique, N. Dhanya and M.C. Divakar, 2011. Importance of flavonoids in therapeutics. Hygeia: J. D. Med., 3(1): 1-18.
-
Slater, G.A., W.J. Swiggard, B.R. Orton, W.D. Flitter, D.E. Goldberg, A. Cerami and G.B. Henderson, 1991. An iron-carboxylate bond links the heme units of malaria pigments. P. Natl. Acad. Sci. USA, 88(2): 325-329.
CrossRef PMid:1988933 PMCid:PMC50803 -
Spiller, D.G., P.G. Bray, R.H. Hughes, S.A. Ward and M.R.H. White, 2002. The pH of the Plasmodium falciparum digestive vacuole: Holy grail or dead-end trail? Trends Parasitol., 18(10): 441-444.
CrossRef -
Sullivan Jr., D.J., 2003. Hemozoin: A biocrystal synthesized during the degradation of Hemoglobin. Biopolymers, 9: 129-163.
-
Talib, W.H. and A.M. Mahasneh, 2010. Antimicrobial, cytotoxicity and phytochemical screening of Jordanian plants used in traditional medicine. Molecules, 15: 1811-1824.
CrossRef PMid:20336015 -
Talib, W.H., M.H. Abu Zarga and A.M. Mahasneh, 2012. Antiproliferative, antimicrobial and apoptosis inducing effects of compounds isolated from Inula viscosa. Molecules, 17: 3291-3303.
CrossRef PMid:22418930 -
Tekwani, B.L. and L.A. Walker, 2005. Targeting the hemozoin synthesis pathway for new anti-malarial drug discovery: Technologies for in vitro ß-hematin formation assay. Comb. Chem. High T. Scr., 8: 63-79.
-
Waller, K.L., R.A. Muhle, L.M. Ursos, P. Horrocks, D. Verdier-Pinard, A.B.S. Sidhu, H. Fujioka, P.D. Roepe and D.A. Fidock, 2003. Chloroquine resistance modulated in vitro by expression levels of the Plasmodium falciparum chloroquine resistance transporter. J. Biol. Chem., 278(35): 33593-33601.
CrossRef PMid:12813054 -
Wollenweber, E., K. Mayer and J.N. Roitman, 1991. Exudat flavonoids of Inula viscosa. Phytochemistry, 30(7): 2445-2446.
CrossRef
Competing interests
The authors have no competing interests.
Open Access Policy
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Copyright
The authors have no competing interests.
|
|
![](http://www.maxwellsci.com/images/BJPT-maxw.jpg) |
ISSN (Online): 2044-2467
ISSN (Print): 2044-2459 |
![Submit Manuscript](../images/sub.jpg) |
Information |
|
|
|
Sales & Services |
|
|
|