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Parasitology Research

, Volume 113, Issue 12, pp 4415–4422 | Cite as

Antiplasmodial activity-aided isolation and identification of quercetin-4’-methyl ether in Chromolaena odorata leaf fraction with high activity against chloroquine-resistant Plasmodium falciparum

  • I. C. Ezenyi
  • O. A. Salawu
  • R. Kulkarni
  • M. Emeje
Original Paper

Abstract

The present study was undertaken to evaluate the antiplasmodial activity of Chromolaena odorata leaf extract and gradient fractions through in vivo and in vitro tests, aimed at identifying its antiplasmodial constituents. Sub-fractions obtained from the most active gradient fraction were further tested for cytotoxicity against THP-1 cells, chloroquine-sensitive (HB3) and chloroquine-resistant (FCM29) Plasmodium falciparum. Our results showed the dichloromethane gradient fraction was most effective, significantly (P < 0.05) suppressing infection by 99.46 % at 100 mg/kg body weight. Amongst its 13 sub-fractions (DF1–DF13), DF11 was highly active, with IC50 of 4.8 and 6.74 μg/ml against P. falciparum HB3 and FCM29, respectively. Cytotoxicity of DF11 was estimated to be above 50 μg/ml, and its separation by column chromatography yielded a flavonoid which was characterized as 3, 5, 7, 3’ tetrahydroxy-4’-methoxyflavone from its spectroscopic data. It significantly suppressed infection (65.43–81.48 %) in mice at 2.5–5 mg/kg doses and compared favourably with the effects of chloroquine and artemisinin. It may therefore serve as a useful phytochemical and antiplasmodial activity marker of C. odorata leaves, which exhibit potential for development as medicine against malaria.

Keywords

Malaria Medicinal plant Plasmodium falciparum Toxicity 

Notes

Acknowledgments

The authors are grateful to Ranarivelo Lalasoanirina and Ratsimbasson Michel of CNARP Madagascar for assistance in conducting the antiplasmodial assays. Ezenyi IC is thankful to Dr Swati Joshi, Dr Dhiman Sarkar, and Dr Sourav Pal of the National Chemical Laboratory Pune and to the Government of India for the RTFDCS fellowship. We also acknowledge Dr. S. Okhale and Mr Abu Garba for conducting HPLC fingerprinting and melting point analysis, respectively. The study was supported by funds from L’Oreal-UNESCO regional fellowship for women in science, awarded to Ezenyi IC.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Barua RN, Sharma RP, Thyagarajan G, Hertz W (1978) Flavonoids of Chromolaena odorata. Phytochemistry 17(10):1807–1808CrossRefGoogle Scholar
  2. Bedi G, Tonzibo ZF, Chopard C, Mahy JP, N’Guessan TY (2004) Study of the anti-pain effects of Chromolaena odorata and Mikania cordata essential oils by action on soybean lipoxygenase L-1. Phys Chem News 15(1):124–127Google Scholar
  3. Bennet TN, Paguio M, Gligorijevic B, Seudieu C. Kosar AD, Davidson E, Roepe PD (2004) Novel, rapid and inexpensive cell-based quantification of antimalarial drug efficacy. Antimicrob Agents Chemother 48(5):1807–1810Google Scholar
  4. Bilia AR, Lazari D, Messori L, Taglioli V, Temperin C, Vincieri FF (2002) Simple and rapid physic-chemical methods to examine action of antimalarial drugs with hemin: its application to Artemisia annua and its constituents. Life Sci 70:769–778PubMedCrossRefGoogle Scholar
  5. Bose PK, Chakrabarti P, Chakravarti S, Dutta SP, Barua AK (1973) Flavonoid constituents of Eupatorium odoratum. Phytochemistry 12:667–668CrossRefGoogle Scholar
  6. Brusotti G, Cesari I, Dentamaro A, Caccialanza G, Massolini G (2014) Isolation and characterization of bioactive compounds from plant resources: the role of analysis in the ethnopharmacological approach. J Pharm Biomed Anal 87:218–228PubMedCrossRefGoogle Scholar
  7. Burkill HM (1985) The useful plants of West tropical Africa, vol 1. Royal boatanic Gardens, KewGoogle Scholar
  8. Cimanga RK, Tona GL, Kambu OK, Mesia GK, Muyembe JJT, Apers S et al (2009) Antimalarial, antiamoebic and cytotoxic activities of some extracts and isolated constituents from the leaves of Morinda morindoides (Baker) Milne-Redh. (Rubiaceae). Recent Prog Med Plants 25:225–242Google Scholar
  9. Ferreira JF, Luthria DL, Sasaki T, Heyerick A (2010) Flavonoids from Artemisia annua L. as antioxidants and their potential synergism with artemisinin against malaria and cancer. Molecules 15(5):3135–3170PubMedCrossRefGoogle Scholar
  10. Ganesh D, Fuehrer HP, Starzengrüber P, Swoboda P, Khan WA, Reismann JA et al (2012) Antiplasmodial activity of flavonol quercetin and its analogues in Plasmodium falciparum: evidence from clinical isolates in Bangladesh and standardized parasite clones. Parasitol Res 110(6):2289–2295PubMedCrossRefGoogle Scholar
  11. Garcia LS (2010) Malaria. Clin Lab Med 30:93–129PubMedCrossRefGoogle Scholar
  12. Kirmizibekmez H, Calis I, Perozzo R, Brun R, Donmez AA, Linden A et al (2004) Inhibiting activities of the secondary metabolites of Phlomis brunneogaleata against parasitic protozoa and plasmodial enoyl-ACP reductase, a crucial enzyme in fatty acid biosynthesis. Planta Med 70:711PubMedCrossRefGoogle Scholar
  13. Ling B, Zhang M, Pang X (2003) Biological activities of the volatile oil from Chromolaena odorata on fungi and insects and its chemical constituent. Tianran Chanwu Yanjiu Yu Kaifa 15(3):183–187Google Scholar
  14. Ling SK, Pisar M, Man S (2007) Platelet-activating factor (PAF) receptor binding antagonist activity of the methanol extracts and isolated flavonoids from Chromolaena odorata (L.) King and Robinson. Biol Pharm Bull 30(6):1150–1152PubMedCrossRefGoogle Scholar
  15. Lorke D (1983) A new approach to practical acute toxicity testing. Arch Toxicol 54:275–287PubMedCrossRefGoogle Scholar
  16. Moalin M, van Strijdonck GP, Bast A, Haenen GR (2012) Competition between ascorbate and glutathione for the oxidized form of methylated quercetin metabolites and analogues: tamarixetin, 4′O-methylquercetin, has the lowest thiol reactivity. J Agric Food Chem 60(36):9292–9297PubMedCrossRefGoogle Scholar
  17. Myhrstad MCW, Carlsen H, Nordstrom O, Blomhoff R, Moskaug JǾ (2002) Flavonoids increase the cellular glutathione level by transactivation of the gamma-glutamylcysteine synthetase catalytical subunit promoter. Free Radic Biol Med 32:386–393PubMedCrossRefGoogle Scholar
  18. National Institute of Health (2011) Guide for the care and use of laboratory animals. http://oacu.od.nih.gov/regs/guide/guide_2011.pdf. Accessed 25 Nov 2013
  19. Nguyen XD, Le KB, Leclercq PAJ (1992) The constituents of the leaf oil of Chromolaena odorata (L.) R. M. King and H. Robinson from Vietnam. Essent Oil Res 4(3):309–310CrossRefGoogle Scholar
  20. Nicolini F, Burmistrova O, Marrero MT, Torres F, Hernández C, Quintana J, Estévez F (2013) Induction of G(2) /M phase arrest and apoptosis by the flavonoid tamarixetin on human leukemia cells. Mol Carcinog. doi: 10.1002/mc.22055 PubMedGoogle Scholar
  21. Ogbonnia SO, Mbaka GO, Anyika EN, Osegbo OM, Igbokwe NH (2010) Evaluation of acute toxicity in mice and subchronic toxicity of hydroethanolic extract of Chromolaena odorata (L.) King and Robinson (Fam. Asteraceae) in rats. Agric Biol N Am 1(5):859–865CrossRefGoogle Scholar
  22. Omodeo-Salè F, Cortelezzi L, Basilico N, Casagrande M, Sparatore A, Taramelli D (2009) Novel antimalarial aminoquinolines: heme binding and effects on normal or Plasmodium falciparum-parasitized human erythrocytes. Antimicrob Agents Chemother 53(10):4339–4344PubMedCentralPubMedCrossRefGoogle Scholar
  23. Peters W, Robinson BL, Tovey G, Rossier JC, Jefford CW (1993) The chemotherapy of rodent malaria. I. The activities of some synthetic 1, 2, 4 - trioxanes against chloroquine-sensitive and chloroquine resistant parasites. Part 3: Observations on ‘Fenozan-50F’ a di-fluorated 3,3′-spirocyclopentane 1,2,4-trioxane. Ann Trop Med Parasitol 87:111–123PubMedGoogle Scholar
  24. Phan T-T, Wang L, See P, Grayer RJ, Chan S-Y, Lee ST (2001) Phenolic compounds of Chromolaena odorata protect cultured skin cells from oxidative damage: implication for cutaneous wound healing. Biol Pharm Bull 24(12):1373–1379PubMedCrossRefGoogle Scholar
  25. Pisutthanan N, Liawruangrath S, Bremner JB, Liawruangrath B (2005) Chemical constituents and biological activities of Chromolaena odorata. Chiang Mai J Sci 32(2):139–148Google Scholar
  26. Roepe PD (2014) To kill or not to kill, that is the question: cytocidal antimalarial drug resistance. Trends Parasitol 30(3):130–135PubMedCrossRefGoogle Scholar
  27. Springfield EP, Eagles PKF, Scott G (2005) Quality assessment of South African herbal medicines by means of HPLC fingerprinting. J Ethnopharmacol 101:75–83PubMedCrossRefGoogle Scholar
  28. Srinivasa RK, Chaudhury PK, Pradhan A (2010) Evaluation of anti-oxidant activities and total phenolic content of Chromolaena odorata. Food Chem Toxicol 48(2):729–732CrossRefGoogle Scholar
  29. Suksamram A, Chotipong A, Suavansri T, Boongird S, Timsuksai P, Vimuttipong S, Chuaynugul A (2004) Antimycobacterial activity and cytotoxicity of flavonoids from the flowers of Chromolaena odorata. Arch Pharm Res 27(5):507–511CrossRefGoogle Scholar
  30. Teffo LS, Aderogba MA, Eloff JN (2010) Antibacterial and antioxidant activities of four Kaempferol methyl ethers isolated from Dodonaea viscosa Jacq. Var. angustifolia leaf extracts. South African Journal of Botany 76(1):25–29Google Scholar
  31. Trager W, Jensen JB (1978) Cultivation of malarial parasites. Nature 273:621–622PubMedCrossRefGoogle Scholar
  32. Velasco-Alinsug MP, Rivero GC, Quibuyen TAO (2005) Isolation of mercury-binding peptides in vegetative parts of Chromolaena odorata. Z Naturforsch C J Biosci 60(3/4):252–259Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • I. C. Ezenyi
    • 1
    • 2
  • O. A. Salawu
    • 1
  • R. Kulkarni
    • 2
  • M. Emeje
    • 3
  1. 1.Department of Pharmacology and ToxicologyNational Institute for Pharmaceutical Research and DevelopmentAbujaNigeria
  2. 2.Organic Chemistry DivisionNational Chemical LaboratoryPuneIndia
  3. 3.Centre for Nanomedicine and Biophysical Drug Delivery, Department of Pharmaceutical Technology and Raw Material DevelopmentNational Institute for Pharmaceutical Research and DevelopmentAbujaNigeria

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