| Peer-Reviewed

Therapeutic Efficacy of Triple Regimen of Artemether, Lumefantrine and Hippocratea africana in the Treatment of Plasmodium berghei Infected Mice

Received: 18 December 2020     Accepted: 25 December 2020     Published: 23 February 2021
Views:       Downloads:
Abstract

Combination therapy is fast replacing monotherapy in the treatment of infectious diseases and Plasmodium resistance to artemisinin–based combination therapies (ACTs) is an emerging challenge. Our study aimed to evaluate the therapeutic efficacy of combining Artemether-Lumefantrine with crude root bark extract of Hippocratea africana, on mice infected with Plasmodium berghei. Forty-five albino mice which weighed 30 - 38g were grouped into five with seven mice in each. The mice were inoculated intraperitoneally with Plasmodium berghei and kept for seven days for the parasitaemia to develop. A daily single dose of 200mg/Kg body weight of extract of H. africana was administered orally for ten days, while therapeutic dose of Artemether-lumefantrine was administered as daily single dose to the relevant groups on the last six days of treatment. A non-parasitized and parasitize untreated groups served as controls. The weights of the animals were recorded before and after treatment. The animals were sacrificed and blood obtained for determination of percentage parasitaemia and the erythrocytes count of the parasitized mice using standard methods. The results showed the mean body weight and percentage body weight changes of parasitized mice treated with combination of ACT plus H. africana not statistically different from those of non-parasitized untreated mice. Parasitized mice treated with ACT plus Extract had a significantly (p < 0.05) reduced percentage parasitaemia when compared with those treated with ACT only. Treatment with ACT plus Extract also showed a significant increase in parasite clearance (100%) when compared to mice treated with either ACT only (93.10%) or Extract only (82.15%). We concluded that combining artemether, lumefantrine and H. africana root bark extract exhibited a good therapeutic efficacy as demonstrated by body weight recovery, parasite clearance and reversion of clinical signs induced by Plasmodium berghei parasitaemia. The triple regimen was more efficacious than ACT alone, and therefore, may be a useful regimen in addressing the emerging problem of resistance of plasmodium species to standards ACTs.

Published in American Journal of Biomedical and Life Sciences (Volume 9, Issue 1)
DOI 10.11648/j.ajbls.20210901.20
Page(s) 78-83
Creative Commons

This is an Open Access article, 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 or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Drug-herb Combination, Hippocratea africana, Artemisinin Therapy, Drug Resistance

References
[1] Kinfu G, Gebre-Selassie S, Fikrie N. Therapeutic Efficacy of Artemether-Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Northern Ethiopia, Malaria Research and Treatment, 2012; 2012: 1-6 https://doi.org/10.1155/2012/548710.
[2] Uwah AF, Ndem JI, Akpan SJ. Combining Artesunate-Amodiaquine and Ciprofloxacin Improves Serum Lipid Profile of Mice Exposed to Plasmodium Berghei Berghei, International Journal of Biomedical Research, 2014; 5 (8): 474-476. DOI: 10.7439/ijbr.
[3] Chris-Ozoko CLE, Naiho AO, Gbagbeke KO, Odafiagwuna P. Effect of Malaria Parasitaemia and Antimalarial/Antioxidant Treatment on Body Weight and Some Reproductive Hormones of Male Mice. Anatomy and Physiology: Current Research, 2020; 2 (320): 1-5. Doi: 10.35248/2161-0940.20.10.320.
[4] McKoy MG, Kong-Quee Iii P, Pepple DJ. In vitro effects of co-incubation of blood with artemether/lumefantrine & vitamin C on the viscosity & elasticity of blood. The Indian Journal of Medical Research, 2016; 143 (5): 577-580. DOI: 10.4103/0971-5916.187105.4.
[5] Djimdé A, Lefèvre G. Understanding the pharmacokinetics of Coartem, Malaria Journal. 2009; 8 (Suppl 1): S [4]. https://europepmc.org/article/pmc/pmc4989830.
[6] Bloland PB, Ettling M, Meek S. Combination therapy for malaria in Africa: hype or hope? Bulletin of the World Health Organization, 2000; 8 (12): 1378–1388.
[7] Haynes RK.. Artemisinin and derivatives: the future for malaria treatment? Current Opinion in Infectious Diseases, 2001; 14: 719–726.
[8] Malomo SO, Adebayo JO, Olorunniji FJ. Decrease in activities of cation ATPases and alkaline phosphatate in kidney andliver of artemether treatead rats. Nigerian Society for Experimental Biology Journal, 2001; 1: 175–182.
[9] Ibrahim HA, Imam IA, Bello AM, Umar U, Muhammad S, Abdullahi SA. The Potential of Nigerian Medicinal Plants as Antimalarial Agent: A Review. International Journal of Science and Technology, 2012; 2 (8): 602-208.
[10] Adebayo JO, Krettli AU. Potential antimalarials from Nigerian aplants: a review Journal of Ethnopharmacology, 2011; 133: 289–30.
[11] Willcox M, Bodeker BG. An overview of ethnobotanical studies on plants used for the treatment of malaria. In: Willcox M, Bodeker G, Rasoanaivo P, editors. Traditional Medicinal Plants and Malaria. Boca Raton: CRC Press, 2004; pp. 187–97.
[12] Ekong US, Udoh DI, Alozie MF, Udofa EJ, Akpaide N I. Investigation of the In vivo Antidiarrhoeal Activity of Hippocratea africana Root Extracts by Model Infection and Protection Test in Mice against Bacterial Isolates from Infectious Diarrhoeal and Gastroenteritis Patients in Uyo, Nigeria. Nigerian Journal of Pharmaceutical and Applied Science Research, 2020; 9 (3): 71-82.
[13] Mark, H., Bart, W., Petra, B. & Meg, C. P. (2014). Hippocratea africana (Willd.) Loes. Flora of Zimbabwe: Species Information: Zimbabwe Flora Team Plus, Nyanga. Retrieved September 2, 2016 from: http://www.zimbabweflora.co.zw/species_id=137110.
[14] Uwah AF. Therapeutic Efficacy And Toxicological Effects Of Concomitant Administration Of Artemether-Lumefantrine With Hippocratea Africana Root And Eremomastax Speciosa Leaf Extracts On Normal And Plasmodium Berghei Infected Mice, A Ph. D Thesis, Department of Medical Laboratory Sciences, University of Calabar, 2017; 85-89.
[15] Okokon JE, Ita JE, Udokpoh AE. The in vivo antimalarial activities of Uvariae chamae and Hippocratea africana. Annals Tropical Medical Parasitology, 2006; 100: 585-590.
[16] Okokon JE, Nwafor PA, Charles U, Dar A, Choudhary MI. Antioxidative burst and hepatoprotective effects of ethanol root extract of Hippocratea africana against paracetamol-induced liver injury, 2013; 51 (7): 872-880.
[17] Rajeswari K, Kuma AR, Rathinam SKM. Phytochemical and anti diarrhoeal activity of Hippocratea africana roots Indian Journal of Research in Pharmacy and Biotechnology 2014; 2 (4): 1357.
[18] 1Adekunle AS, Adekunle OC, Egbewale BE. Serum Status of Selected Biochemical Parameters in Malaria: An Animal Model. Biomedical Research, 2007; 18 (2): 109-113.
[19] Greenwood B. M., Armstrong J. R. M. (1991) Comparison of two simple methods for determining malaria parasite density. Transactions Royal Society Tropical Medicine and Hygiene; 85: 186-188.20.
[20] Gardiner P, Graham RE, Legedza AT, Eisenberg DM, Phillips RS. Factors associated with dietary supplement use among prescription medication users. Archive of Internal Medicine, 2006; 166: 1968–1974.
[21] Kennedy J, Wang CC, Wu CH. Patient Disclosure about Herb and Supplement Use among Adults in the US. Evididence Based Complementary Alternative Medicine, 2008; 5: 451–456.
[22] Gharoro EP, Igbafe AA. Pattern of drug use among antenatal patients in Benin City. Nigeria Medical Science Monitor. 2000; 6: 84–87.
[23] Giveon SM, Liberman N, Klang S, Kahan E. Are people who use ‘natural drugs’ aware of their potentially harmful side effects and reporting to family physician? Patient Educ. Couns. 2004; 53: 5–11 DOI. 10.1016/S0738-3991(03)00241-6.
[24] World Health Organization (WHO). Antimalarial Drug Efficacy and Resistance, World malaria report 2015, WHO press, Geneva, Switzerland 2015; pp 49 -51.
[25] Franke-Fayard B, Fonager J, Braks A, Khan SM, Janse CJ. Sequestration and Tissue Accumulation of Human Malaria Parasites: Can We Learn Anything from Rodent Models of Malaria? PLoS Pathogenesis, 2010; 6 (9): e1001032.
[26] Uwah AF, Ndem JI, Peter AI. Artesunate-Amodiaquine and Ciprofloxacin Combination Improves Biochemical and Histological Markers of Renal Function of Malaria Infected Mice. Indo American Journal of Pharm Research, 2014; 4 (07).
[27] Boon NA, Colledge NR, Walker BR, Hunter JAA Davidson’s Principle and Principle of Medicine. 20th edn. Elsevier: Churchill Livingstone. 2006; pp. 445-485.
[28] Dascombe MJ, Sidara JY. The Absence of Fever in Rat Malaria is Associated with Increased Turnover of 5-Hydroxytryptamine in the Brain. In: Milton A. S. (eds) Temperature Regulation. Advances in Pharmacological Sciences. Birkhäuser, Basel 1994; pp 47-52 https://doi.org/10.1007/978-3-0348-8491-4_8.
[29] Uraku AJ. Hepatoprotective effects of Plasmodium berghei infected swiss mice treated with some plant extracts. J Pharm Allied Health Sci. 2016; 6: 1-7.
[30] Shimada M, Hirose Y, Shimizu K. et al. Upper gastrointestinal pathophysiology due to mouse malaria Plasmodium berghei ANKA infection. Trop Med Health 47, 18 (2019). https://doi.org/10.1186/s41182-019-0146-9.
[31] Ndem JI, Eteng MU, Uwah AF. Effect of Hippocratea africana Root Bark Extract on Lipid Profile of Female and Male Albino Wistar Rats. Journal of Scientific Research and Reports, 2015; 3 (19): 2574-2583.
[32] Rayo CCM, Croft SI, Phillipson JD. Natural product as sources of antiprotozoal drugs: Current opinion in anti-infective investigational. Drugs, 2002; 2, 47-62.
Cite This Article
  • APA Style

    Anthony Fidelis Uwah, Augustine Ini Lawrence Bassey, Innocent Asukwo Edagha, Blessing Obinaju Effiong. (2021). Therapeutic Efficacy of Triple Regimen of Artemether, Lumefantrine and Hippocratea africana in the Treatment of Plasmodium berghei Infected Mice. American Journal of Biomedical and Life Sciences, 9(1), 78-83. https://doi.org/10.11648/j.ajbls.20210901.20

    Copy | Download

    ACS Style

    Anthony Fidelis Uwah; Augustine Ini Lawrence Bassey; Innocent Asukwo Edagha; Blessing Obinaju Effiong. Therapeutic Efficacy of Triple Regimen of Artemether, Lumefantrine and Hippocratea africana in the Treatment of Plasmodium berghei Infected Mice. Am. J. Biomed. Life Sci. 2021, 9(1), 78-83. doi: 10.11648/j.ajbls.20210901.20

    Copy | Download

    AMA Style

    Anthony Fidelis Uwah, Augustine Ini Lawrence Bassey, Innocent Asukwo Edagha, Blessing Obinaju Effiong. Therapeutic Efficacy of Triple Regimen of Artemether, Lumefantrine and Hippocratea africana in the Treatment of Plasmodium berghei Infected Mice. Am J Biomed Life Sci. 2021;9(1):78-83. doi: 10.11648/j.ajbls.20210901.20

    Copy | Download

  • @article{10.11648/j.ajbls.20210901.20,
      author = {Anthony Fidelis Uwah and Augustine Ini Lawrence Bassey and Innocent Asukwo Edagha and Blessing Obinaju Effiong},
      title = {Therapeutic Efficacy of Triple Regimen of Artemether, Lumefantrine and Hippocratea africana in the Treatment of Plasmodium berghei Infected Mice},
      journal = {American Journal of Biomedical and Life Sciences},
      volume = {9},
      number = {1},
      pages = {78-83},
      doi = {10.11648/j.ajbls.20210901.20},
      url = {https://doi.org/10.11648/j.ajbls.20210901.20},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajbls.20210901.20},
      abstract = {Combination therapy is fast replacing monotherapy in the treatment of infectious diseases and Plasmodium resistance to artemisinin–based combination therapies (ACTs) is an emerging challenge. Our study aimed to evaluate the therapeutic efficacy of combining Artemether-Lumefantrine with crude root bark extract of Hippocratea africana, on mice infected with Plasmodium berghei. Forty-five albino mice which weighed 30 - 38g were grouped into five with seven mice in each. The mice were inoculated intraperitoneally with Plasmodium berghei and kept for seven days for the parasitaemia to develop. A daily single dose of 200mg/Kg body weight of extract of H. africana was administered orally for ten days, while therapeutic dose of Artemether-lumefantrine was administered as daily single dose to the relevant groups on the last six days of treatment. A non-parasitized and parasitize untreated groups served as controls. The weights of the animals were recorded before and after treatment. The animals were sacrificed and blood obtained for determination of percentage parasitaemia and the erythrocytes count of the parasitized mice using standard methods. The results showed the mean body weight and percentage body weight changes of parasitized mice treated with combination of ACT plus H. africana not statistically different from those of non-parasitized untreated mice. Parasitized mice treated with ACT plus Extract had a significantly (p H. africana root bark extract exhibited a good therapeutic efficacy as demonstrated by body weight recovery, parasite clearance and reversion of clinical signs induced by Plasmodium berghei parasitaemia. The triple regimen was more efficacious than ACT alone, and therefore, may be a useful regimen in addressing the emerging problem of resistance of plasmodium species to standards ACTs.},
     year = {2021}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Therapeutic Efficacy of Triple Regimen of Artemether, Lumefantrine and Hippocratea africana in the Treatment of Plasmodium berghei Infected Mice
    AU  - Anthony Fidelis Uwah
    AU  - Augustine Ini Lawrence Bassey
    AU  - Innocent Asukwo Edagha
    AU  - Blessing Obinaju Effiong
    Y1  - 2021/02/23
    PY  - 2021
    N1  - https://doi.org/10.11648/j.ajbls.20210901.20
    DO  - 10.11648/j.ajbls.20210901.20
    T2  - American Journal of Biomedical and Life Sciences
    JF  - American Journal of Biomedical and Life Sciences
    JO  - American Journal of Biomedical and Life Sciences
    SP  - 78
    EP  - 83
    PB  - Science Publishing Group
    SN  - 2330-880X
    UR  - https://doi.org/10.11648/j.ajbls.20210901.20
    AB  - Combination therapy is fast replacing monotherapy in the treatment of infectious diseases and Plasmodium resistance to artemisinin–based combination therapies (ACTs) is an emerging challenge. Our study aimed to evaluate the therapeutic efficacy of combining Artemether-Lumefantrine with crude root bark extract of Hippocratea africana, on mice infected with Plasmodium berghei. Forty-five albino mice which weighed 30 - 38g were grouped into five with seven mice in each. The mice were inoculated intraperitoneally with Plasmodium berghei and kept for seven days for the parasitaemia to develop. A daily single dose of 200mg/Kg body weight of extract of H. africana was administered orally for ten days, while therapeutic dose of Artemether-lumefantrine was administered as daily single dose to the relevant groups on the last six days of treatment. A non-parasitized and parasitize untreated groups served as controls. The weights of the animals were recorded before and after treatment. The animals were sacrificed and blood obtained for determination of percentage parasitaemia and the erythrocytes count of the parasitized mice using standard methods. The results showed the mean body weight and percentage body weight changes of parasitized mice treated with combination of ACT plus H. africana not statistically different from those of non-parasitized untreated mice. Parasitized mice treated with ACT plus Extract had a significantly (p H. africana root bark extract exhibited a good therapeutic efficacy as demonstrated by body weight recovery, parasite clearance and reversion of clinical signs induced by Plasmodium berghei parasitaemia. The triple regimen was more efficacious than ACT alone, and therefore, may be a useful regimen in addressing the emerging problem of resistance of plasmodium species to standards ACTs.
    VL  - 9
    IS  - 1
    ER  - 

    Copy | Download

Author Information
  • Department of Medical Biochemistry, Faculty of Basic Medical Science, College of Health Sciences, University of Uyo, Uyo, Nigeria

  • Department of Clinical Pharmacology and Therapeutics, Faculty of Basic Clinical Science, College of Health Sciences, University of Uyo, Uyo, Nigeria

  • Department of Human Anatomy, Faculty of Basic Medical Science, College of Health Sciences, University of Uyo, Uyo, Nigeria

  • Department of Medical Biochemistry, Faculty of Basic Medical Science, College of Health Sciences, University of Uyo, Uyo, Nigeria

  • Sections