Abstract
Antimalarial drug resistance is the main therapeutic challenge to the control of the disease, making the search for new compounds as alternative treatments of central importance. Propolis has a long history of medicinal use due to its antifungal, antibacterial and antiprotozoal properties. The present study therefore aimed to evaluate the antimalarial activity of the Saudi propolis methanolic extract against Plasmodium chabaudi infection in mice. To this end, albino mice were divided into five groups: the first group was the normal control; the second, third, fourth and fifth groups were infected intraperitoneally with 106 P. chabaudi-parasitized erythrocytes. The last three groups of mice were gavaged with 100 μl of propolis extract (PE) at a dose of 25, 50 and 100 mg PE/kg, respectively, once daily for 7 days. PE significantly suppressed the parasitaemia and showed significant efficacy in ameliorating anaemic conditions in P. chabaudi-infected mice in a dose-dependent manner. Histological investigation of the spleen tissue of treated and untreated mice further supports the antimalarial potential of PE. In addition, our study proved that Saudi PE reduced oxidative damage by decreasing the malondialdehyde (MDA) and increasing the catalase (CAT) activity and the glutathione (GSH) levels. Also, Saudi PE increased the level of some pro-inflammatory cytokines such as IFN-γ, TNF-α, GM-CSF and G-CSF, with the most effective dose being 100 mg PE/kg. In conclusion, PE showed antimalarial and antioxidant activities and provided protection against spleen tissue damage in P. chabaudi-infected mice.
Similar content being viewed by others
References
Adegbolagun OM, Emikpe BO, Woranola IO, Ogunremi Y (2013) Synergistic effect of aqueous extract of Telfaria occidentalis on the biological activities of artesunate in Plasmodium berghei infected mice. Afr Health Sci 13:970–976
Aebi HU (ed) (1984) Methods in enzymatic analysis. Academic, New York, pp 276–286
Angulo I, Fresno M (2002) Cytokines in the pathogenesis of and protection against malaria. Clin Diagn Lab Immunol 9:1145–1152
Bankova V, Trusheva B, Popova M (2008) New developments in propolis chemical diversity studies (since 2000). In: Oršolic N, Bašić I (eds) Scientific evidence of the use of propolis in ethnomedicine
Barreda DR, Hanington PC, Belosevic M (2004) Regulation of myeloid development and function by colony stimulating factors. Dev Comp Immunol 28:509–554
Beutler E, Duron O, Kelly B (1963) Improved method for determination of blood glutathione. J Lab Clin Med 61:882
Björkman A (2002) Malaria associated anaemia, drug resistance and antimalarial combination therapy. Int J Parasitol 32:1637–1643
Boura M, Frita R, Gois A, Carvalho T, Hanscheid T (2013) The hemozoin conundrum: is malaria pigment immune activating, inhibiting, or simply a bystander? Trends Parasitol 29:469–476
Bruna-Romero O, Schmieg J, Del Val M, Buschle M, Tsuji M (2003) The dendritic cell-specific chemokine, dendritic cell-derived CC chemokine 1, enhances protective cell-mediated immunity to murine malaria. J Immunol 170:3195–3203
Bueno-Silva B, Alencar SM, Koo H, Ikegaki M, Silva GV, Napimoga MH, Rosalen PL (2013) Anti-inflammatory and antimicrobial evaluation of neovestitol and vestitol isolated from Brazilian red propolis. J Agric Food Chem 61:4546–4550
Burdock GA (1998) Review of the biological properties and toxicity of bee propolis (propolis). Food Chem Toxicol 36:347–363
Del Portillo HA, Ferrer M, Brugat T, Martin-Jaular L, Langhorne J, Lacerda MV (2012) The role of the spleen in malaria. Cell Microbiol 14:343–355
Falcão SI, Vale N, Cos P, Gomes P, Freire C, Maes L, Vilas-Boas M (2014) In vitro evaluation of Portuguese propolis and floral sources for antiprotozoal, antibacterial and antifungal activity. Phytother Res 28:437–743
Farnesi AP, Aquino-Ferreira R, De Jong D, Bastos JK, Soares AE (2009) Effects of stingless bee and honey bee propolis on four species of bacteria. Genet Mol Res 8:635–640
Fell AH, Smith NC (1998) Immunity to asexual blood stages of Plasmodium: is resistance to acute malaria adaptive or innate? Parasitol Today 14:364–369
Freitas SF, Shinohara L, Sforcin JM, Guimarães S (2006) In vitro effects of propolis on Giardia duodenalis trophozoites. Phytomedicine 13:170–175
Gamo FJ, Sanz LM, Vidal J, de Cozar C, Alvarez E, Lavandera JL, Vanderwall DE, Green DV, Kumar V, Hasan S, Brown JR, Peishoff CE, Cardon LR, Garcia-Bustos JF (2010) Thousands of chemical starting points for antimalarial lead identification. Nature 465:305–310
Gao W, Wu J, Wei J, Pu L, Guo C, Yang J, Yang M, Luo H (2014) Brazilian green propolis improves immune function in aged mice. J Clin Biochem Nutr 55:7–10
Hafiz TA, Mubaraki MA, Al-Quraishy S, Dkhil MA (2016) The potential role of Punica granatum treatment on murine malaria-induced hepatic injury and oxidative stress. Parasitol Res 115:1427–1433
Herrera CL, Alvear M, Barrientos L (2010) The antifungal effect of six commercial extracts of Chilean propolis on Candida spp. Cien Inv Agr 37:75–84
Huang S, Zhang C, Wang K, Li GQ, Hu F (2014) Recent advances in the chemical composition of propolis. Molecules 19:19610–19632
Iwalokun BA (2008) Enhanced antimalarial effects of chloroquine by aqueous Vernonia amygdalina leaf extract in mice infected with chloroquine resistant and sensitive Plasmodium berghei strains. Afr Health Sci 8:25–35
Jabbarzare M, Chin VK, Talib H, Yam MF, Adam SK, Hassan H, Abdul Majid R, Mat Taib CN, Mohd Moklas MA, Taufik Hidayat M, Mohd Sidek H, Basir R (2015) Interleukin-18 antagonism improved histopathological conditions of malaria infection in mice. Iran J Parasitol 10:389–401
Kalia P, Kumar NR, Harjai K (2014) Studies on the effect of ethanolic extract of propolis in BALB/c mice. J App Nat Sci 6:638–643
Kalia P, Kumar NR, Harjai K (2016) Effect of propolis extract on hematotoxicity and histological changes induced by Salmonella enteric serovar Typhimurium in BALB/c mice. Arch Biol Sci 68:385–391
Kim TS, Sohn Y, Kim JY, Lee WJ, Na BK, Kang YJ, Lee HW (2014) Detection of antibodies against the CB9 to ICB10 region of merozoite surface protein-1 of Plasmodium vivax among the inhabitants in epidemic areas. Malar J 13:311
Kismet K, Sabuncuoglu MZ, Kilicoglu SS, Kilicoglu B, Devrim E, Erel S, Sunay AE, Erdemli E, Durak I, Akkus MA (2008) Effect of propolis on oxidative stress and histomorphology of liver tissue in experimental obstructive jaundice. Eur Surg Res 41:231–237
Komlaga G, Agyare C, Dickson RA, Mensah MLK, Annan K, Loiseau PM, Champy P (2015) Medicinal plants and finished marketed herbal products used in the treatment of malaria in the Ashanti region, Ghana. J Ethnopharmacol 172:333–346
Lawal B, Shittu OK, Abubakar AN, Haruna GM, Saidu S, Ossai PC (2015a) Haematopoetic effect of methanol extract of Nigerian honey bee (Apis mellifera) propolis in mice. J Coast Life Med 3:648–651
Lawal B, Shittu OK, Kabiru AY, Jigam AA, Umar MB, Berinyuy EB, Alozieuwa BU (2015b) Potential antimalarials from African natural products: a review. J Intercult Ethnopharmacol 4:318–343
Levesque MA, Sullivan AD, Meshnick SR (1999) Splenic and hepatic hemozoin in mice after malaria parasite clearance. J Parasitol 85:570–573
Ley B, Alam MS, Thriemer K, Hossain MS, Kibria MG, Auburn S, Poirot E, Price RN, Khan WA (2016) G6PD deficiency and antimalarial efficacy for uncomplicated malaria in Bangladesh: a prospective observational study. PLoS One 11:e0154015
Lima LD, Andrade SP, Campos PP, Barcelos LS, Soriani FM, Moura SA, Ferreira MA (2014) Brazilian green propolis modulates inflammation, angiogenesis and fibrogenesis in intraperitoneal implant in mice. BMC Complement Altern Med 14:177
Lopes D, Rungsihirunrat K, Nogueira F, Seugorn A, Gil JP, Do Rosário VE, Cravo P (2002) Molecular characterisation of drug-resistant Plasmodium falciparum from Thailand. Malar J 14:1–12
Lubbad MY, Al-Quraishy S, Dkhil MA (2015) Antimalarial and antioxidant activities of Indigofera oblongifolia on Plasmodium chabaudi-induced spleen tissue injury in mice. Parasitol Res 114:3431–3438
Machado JL, Assuncao AK, da Silva MC, Dos Reis AS, Costa GC, Arruda Dde S, Rocha BA, Vaz MM, Paes AM, Guerra RN et al (2012) Brazilian green propolis: anti-inflammatory property by an immunomodulatory activity. J Evid Based Complementary Alternat Med 2012:157652
McCall MB, Sauerwein RW (2010) Interferon-gamma central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria. J Leukoc Biol 88:1131–1143
Menendez C, Fleming AF, Alonso PL (2000) Malaria-related anaemia. Parasitol Today 16:469–676
Missima F, Sforcin JM (2008) Green Brazilian propolis action on macrophages and lymphoid organs of chronically stressed mice. J Evid Based Complementary Alternat Med 5:71–75
Nega D, Assefa A, Mohamed H, Solomon H, Woyessa A, Assefa Y, Kebede A, Kassa M (2016) Therapeutic efficacy of Artemether-Lumefantrine (Coartem®) in treating uncomplicated P. falciparum malaria in Metehara, Eastern Ethiopia: regulatory clinical study. PLoS One 11:e0154618
Nogueira CR, Lopes LMX (2011) Antiplasmodial natural products. Molecules 16:2146–2190
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Olayemi KI (2014) Therapeutic potentials of Nigerian insect-propolis against malarial parasite, Plasmodium bergei (Haemosorida plasmodidae). Am J Drug Discov Dev 4:241–247
Paulino N, Teixeira C, Martins R, Scremin A, Dirsch VM, Vollmar AM, Abreu SR, de Castro SL, Marcucci MC (2006) Evaluation of the analgesic and anti-inflammatory effects of a Brazilian green propolis. Planta Med 72:899–906
Rapoport AP, Abboud CN, DiPersio JF (1992) Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF): receptor biology, signal transduction, and neutrophil activation. Blood Rev 6:43–57
Rizk SM, El-Maraghy SA, Nassar NN (2014) A novel role for SIRT-1 in L-arginine protection against STZ induced myocardial fibrosis in rats. PLoS One 9:e114560
Simone-Finstrom M, Spivak M (2010) Propolis and bee health: the natural history and significance of resin use by honey bees. Apidologie 41:295–311
Singla S, Kumar NR, Kaur J (2014) In vivo studies on the protective effect of propolis on doxorubicin induced toxicity in liver of male rats. Toxicol Int 21:191–195
Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI (2005) The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434:214–217
Sönmez MF, Çilenk KT, Karabulut D, Ünalmış S, Deligönül E, Öztürk İ, Kaymak E (2016) Protective effects of propolis on methotrexate-induced testis injury in rat. Biomed Pharmacother 79:44–51
Stevenson MM, Riley EM (2004) Innate immunity to malaria. Nat Rev Immunol 4:169–180
Szliszka E, Kucharska AZ, Sokol-Letowska A, Mertas A, Czuba ZP, Krol W (2013) Chemical composition and anti-inflammatory effect of ethanolic extract of Brazilian green propolis on activated J774A.1 macrophages. J Evid Based Complementary Alternat Med 2013:976415
Teixeira EW, Negri G, Renata MSAM, Message D, Salatino A (2005) Plant origin of green propolis: bee behavior, plant anatomy and chemistry. Evid Based Complement Alternat Med 2:85–92
Toreti VC, Sato HH, Pastore GM, Park YK (2013) Recent progress of propolis for its biological and chemical compositions and its botanical origin. Evid Based Complement Alternat Med 2013:697390
Ushach I, Zlotnik A (2016) Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage. J Leukoc Biol 100:481–489
WHO (2014) World malaria report 2014. WHO Press, Geneva
WHO (2015) WHO traditional medicine strategy: 2002–2005. WHO Press, Geneva
Wunderlich F, Stübig H, Königk E (1982) Development of Plasmodium chabaudi in mouse red blood cells: structural properties of the host and parasite membranes. J Protozool 29:60–66
Xu X, Sun L, Dong J, Zhang H (2009) Breaking the cells of rape bee pollen and consecutive extraction of functional oil with superficial carbon oxide. Innovative Food Sci Emerg Technol 10:42–46
Zhao JQ, Wen YF, Bhadauria M, Nirala SK, Sharma A, Shrivastava S, Shukla S, Agrawal OP, Mathur R (2009) Protective effects of propolis on inorganic mercury induced oxidative stress in mice. Indian J Exp Biol 47:264–269
Acknowledgements
This research project was supported by a grant from the “Research Center for the Female Scientific and Medical College”, Deanship of Scientific Research, King Saud University.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This work was approved by the state authorities and followed the Saudi Arabian rules for animal protection.
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
AlGabbani, Q., Mansour, L., Elnakady, Y.A. et al. In vivo assessment of the antimalarial and spleen-protective activities of the Saudi propolis methanolic extract. Parasitol Res 116, 539–547 (2017). https://doi.org/10.1007/s00436-016-5318-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-016-5318-5