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In vitro sensitivity of Plasmodium falciparum field isolates to extracts from Cameroonian Annonaceae plants

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Abstract

In a search for new plant-derived antimalarial extracts, 19 fractions were obtained from three Annonaceae species, Uvariopsis congolana (leaf, stem), Polyalthia oliveri (stem bark), and Enantia chlorantha (stem, stem bark) with yields ranging from 0.33% to 4.60%. The extracts were prepared from 500 g of each plant part, using organic solvents to afford five methanolic fractions (acetogenin rich), five water fractions, five hexane fractions, and four interface precipitates. Evaluation of the activity of fractions in vitro against field isolates of the malaria parasite Plasmodium falciparum showed that acetogenin-rich fractions and interface precipitates were the most potent, with IC50 values ranging from 0.05 to 8.09 μg/ml. Sensitivity of parasite isolates to plant extracts varied greatly, with over 100-fold difference from isolate to isolate in some cases. The active acetogenin-rich fractions and interface precipitates were assessed in combination with chloroquine in the same conditions, and showed additive interaction in the huge majority of cases. Synergistic interactions were found in some cases with acetogenin-rich fractions. Acute toxicity of promising fractions was evaluated through oral administration in Swiss albino mice. Tested fractions appeared to be safe, with LD50 values higher than 2 g/kg. In summary, acetogenin-rich fractions from Annonaceae species showed high potency against P. falciparum field isolates and safety by oral administration in mice, supporting their detailed investigation for antimalarial drug discovery.

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References

  • Adjanohoun JE, Aboubakar N, Dramane K, Ebot ME, Ekpere JA, Enoworock EG, Focho D, Gbile ZO, Kamanyi A, Kamsu KJ, Keita A, Mbenkum T, Mbi CN, Mbiele AC, Mbome JC, Muberu NK, Nancy WL, Kongmeneck B, Satabie B, Sofowora A, Tamze V, Wirmum CK (1996) Traditional medicine and pharmacopoeia: contribution to ethnobotanical and floristic studies in Cameroon. Ed. Organization of African Unity: Scientific, Technical and Research Commission, Addis Ababa 641p

  • Agbaje EO, Onabanjo AO (1991) The effects of extracts of Enantia chlorantha in malaria. Ann Trop Med Parasitol 85(6):585–590

    PubMed  CAS  Google Scholar 

  • Agbaje EO, Onabanjo AO (1994) Toxicological study of the extracts of anti-malarial medicinal plant Enantia chlorantha. Cent Afr J Med 40(3):71–73

    PubMed  CAS  Google Scholar 

  • Agomo PU, Idigo JC, Afolabi BM (1992) Antimalarial medicinal plants and their impact on cell populations in various organs of mice. Afr J Med & Med Sci 21(2):39–46

    CAS  Google Scholar 

  • Alali FQ, Liu XX, Mc Laughlin JL (1999) Annonaceous acetogenins: recent progress. J Nat Prod 62:504–540

    Article  PubMed  CAS  Google Scholar 

  • Bagavan A, Rahuman AA, Kaushik NK, Sahal D (2010) In vitro antimalarial activity of medicinal plant extracts against Plasmodium falciparum. Parasitol Res. doi:10.1007/s00436-010-2034-4

    Google Scholar 

  • Boyom FF, Madiesse Kemgne EA, Tepongning R, Ngouana V, Mbacham WF, Tsamo E, Amvam Zollo PH, Gut J, Rosenthal PJ (2009) Antiplasmodial activity of extracts from seven medicinal plants used in malaria treatment in Cameroon. J Ethnopharmacol 123:483–488

    Article  PubMed  Google Scholar 

  • Boyom FF, Ngouana V, Madiesse Kemgne EA, Amvam Zollo PH, Menut C, Bessiere JM, Gut J, Rosenthal PJ (2011a) Antiplasmodial volatile extracts from Cleistopholis patens Engler & Diels and Uvariastrum pierreanum Engl. (Engl. & Diels) (Annonaceae) growing in Cameroon. Parasitol Res 108:1211–1217

    Article  PubMed  Google Scholar 

  • Boyom FF, Tsouh Fokou PV, Tchokouaha Yamthe LR, Ngoutane Mfopa A, Madiesse Kemgne EA, Mbacham WF, Tsamo E, Amvam Zollo PH, Gut J, Rosenthal PJ (2011b) Potent antiplasmodial extracts from Cameroonian Annonaceae. J Ethnopharmacol 134:717–724

    Article  PubMed  Google Scholar 

  • Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM et al (2009) Artemisinin resistance in Plasmodium falciparum malaria. New Engl J Med 361(5):455–467

    Article  PubMed  CAS  Google Scholar 

  • Fernando SD, Rodrigo C, Rajapakse S (2010) The ‘hidden’ burden of malaria: cognitive impairment following infection. Malaria J 9(366):1–11

    Google Scholar 

  • Fidock DA, Rosenthal PJ, Croft SL, Brun R, Nwaka S (2004) Antimalarial drug discovery: efficacy models for compound screening. Nat Rev Drug Discov 3:509–520

    Article  PubMed  CAS  Google Scholar 

  • Ghosh MN (1984) In statistical analysis, fundamentals of experimental pharmacology, 2nd edn. Calcutta, Scientific Book Agency, pp 153–189

    Google Scholar 

  • Guadaño A, Gutiérrez C, DelaPeña E, Cortes D, González CA (2000) Insecticidal and mutagenic evaluation of two annonaceous acetogenins. J Nat Prod 63:773–776

    Article  PubMed  Google Scholar 

  • Ichino C, Soonthornchareonnon N, Chuakul W, Kiyohara H, Ishiyama A, Sekiguchi H, Namatame M, Otoguro K, Omura S, Yamada H (2006) Screening of Thai medicinal plant extracts and their active constituents for in vitro antimalarial activity. Phytother Res 20(4):307–309

    Article  PubMed  CAS  Google Scholar 

  • John CC, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, Wu B, Boivin MJ (2008) Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics 122:e92–e99

    Article  PubMed  Google Scholar 

  • Joshi SC, Priya SE, Venkataraman (2007) Acute and sub acute toxicities on the polyherbalantidiabetic formulation Diakyur in experimental animal models. J Health Sci 53(2):245–249

    Article  Google Scholar 

  • Kanokmedhakul S, Kanokmedhakul K, Kantikeaw I, Phonkerd N (2006) 2-substituted furans from the roots of Polyalthia evecta. J Nat Prod 69(1):68–72

    Article  PubMed  CAS  Google Scholar 

  • Kanokmedhakul S, Kanokmedhakul K, Lekphrom R (2007) Bioactive constituents of the roots of Polyalthia cerasoides. J Nat Prod 70(9):1536–1538

    Article  PubMed  CAS  Google Scholar 

  • Kimbi HK, Fagbenro-Beyioku AF (1996) Efficacy of Cymbopogon giganteus and Enantia chlorantha against chloroquine resistant Plasmodium yoelii nigeriensis. East Afr Med J 73(10):636–637

    PubMed  CAS  Google Scholar 

  • Krief S, Huffman MA, Sévenet T, Hladik CM, Grellier P, Loiseau PM, Wrangham RW (2006) Bioactive properties of plant species ingested by chimpanzees (Pan troglodytes schweinfurthii) in the Kibale National Park, Uganda. Am J Primatol 68(1):51–71

    Article  PubMed  CAS  Google Scholar 

  • Lewis MA, Arnason JT, Philogene BJR, Rupprecht JK, McLaughlin JL (1993) Inhibition of respiration at site I by asimicin, an insecticidal acetogenin of the Pawpaw Asimina triloba (Annonaceae). Pest Biochem Physiol 45:15–23

    Article  CAS  Google Scholar 

  • Meletiadis J, Pournaras S, Roilides E, Walsh TJ (2009) Defining fractional inhibitory concentration index cutoffs foradditive interactions based on self-drug additive combinations, Monte Carlo simulation analysis and in vitro-in vivo correlation data for antifungal drug combinations against Aspergillus fumigatus. Antimicrob Agents Chemother. doi:10.1128/AAC.00999-09

    Google Scholar 

  • Miller LC, Tainter ML (1944) Estimation of ED50 and its error by means of log-probit graph paper. Proceeding of the Soc Exp Biol Med 57:261

    CAS  Google Scholar 

  • Morré DJ, DeCabo R, Farley C, Oberlies NH, McLaughlin JL (1995) Mode of action of bullatacin, a potent antitumor acetogenin: inhibition of NADH oxidase activity HeLa and HL-60 but not liver, plasma membranes. Life Sci 56:343–348

    Article  PubMed  Google Scholar 

  • OECD (2008) Guidelines for the testing of chemicals/section 4: health effects—test no. 425: acute oral toxicity: up-and-down procedure. OECD Publishing, Paris

    Book  Google Scholar 

  • Rakotomanga M, Razakantoanina V, Raynaud S, Loiseau PM, Hocquemiller R, Jaureguiberry G (2004) Antiplasmodial activity of acetogenins and inhibitory effect on Plasmodium falciparum adenylatetranslocase. J Chemother 16:350–356

    PubMed  CAS  Google Scholar 

  • Rupprecht JK, Chang JM, McLaughin JL (1990) Annonaceous acetogenins: a review. J Nat Prod 53:237–278

    Article  PubMed  CAS  Google Scholar 

  • Sanon S, Azas N, Gasquet M, Ollivier E, Mahiou V, Barro N, Cuzin-Ouattara N, Traore AS, Esposito F, Balansard G, Timon-David P (2003) Antiplasmodial activity of alkaloid extracts from Pavetta crassipes (K. Schum) and Acanthospermum hispidum (DC), two plants used in traditional medicine in Burkina Faso. Parasitol Res 90:314–317

    Article  PubMed  CAS  Google Scholar 

  • Singh A, Rosenthal PJ (2001) Comparison of efficacies of cysteine protease inhibitors against five strains of Plasmodium falciparum. Antimicrob Agents Chemother 45:949–951

    Article  PubMed  CAS  Google Scholar 

  • Vennerstrom JL, Klayman DL (1998) Protoberberine alkaloids as antimalarials. J Med Chem 31(6): 1084–1087

    Google Scholar 

  • Wallace CD, Wallace HA (2001) In principles and method of toxicology, 4th edn. Taylor and Francis, Philadelphia, pp 871–873

    Google Scholar 

  • WHO (2010) World Malaria Report. WHO Library Cataloguing-in-Publication Data 1–137

Download references

Acknowledgments

This investigation was supported by a MIM/TDR grant (A80689) to FFB, and Fobang Foundation. The authors gratefully acknowledge the expertise of the laboratory of PJR. We also acknowledge the practical help of Mr. Victor Nana of the Cameroon National Herbarium, and Dr. Nole Tsabang of the Institute of Medical Research and Medicinal Plants Studies for their assistance with the ethnobotanical survey, collection, and identification of plant materials.

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Authors and Affiliations

  1. Laboratory of Phytobiochemistry and Medicinal Plants Study, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon

    Eugénie Aimée Madiesse Kemgne, Fabrice Fekam Boyom & Paul Henri Amvam Zollo

  2. Laboratory for Public Health Research Biotechnologies, Biotechnology Centre, University of Yaoundé I, Yaoundé, Cameroon

    Eugénie Aimée Madiesse Kemgne & Wilfred Fon Mbacham

  3. Laboratory of Natural Products, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon

    Etienne Tsamo

  4. Division of Infectious Diseases, Department of Medicine, University of California San Francisco, San Francisco, CA, 94943, USA

    Philip J. Rosenthal

  5. Laboratory for Public Health Research Biotechnologies, Biotechnology Centre, University of Yaoundé I, P.O. Box 8094, Yaoundé, Cameroon

    Wilfred Fon Mbacham

Authors
  1. Eugénie Aimée Madiesse Kemgne
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  2. Wilfred Fon Mbacham
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  3. Fabrice Fekam Boyom
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  4. Paul Henri Amvam Zollo
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  5. Etienne Tsamo
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  6. Philip J. Rosenthal
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Corresponding authors

Correspondence to Wilfred Fon Mbacham or Fabrice Fekam Boyom.

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Kemgne, E.A.M., Mbacham, W.F., Boyom, F.F. et al. In vitro sensitivity of Plasmodium falciparum field isolates to extracts from Cameroonian Annonaceae plants. Parasitol Res 110, 109–117 (2012). https://doi.org/10.1007/s00436-011-2456-7

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  • DOI: https://doi.org/10.1007/s00436-011-2456-7

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