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Safety assessment and antimalarial property of methanol extract of Fagara zanthoxyloides root-bark on Plasmodium berghei-infected mice

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Abstract

Fagara zanthoxyloides Lam. (Rutaceae) is an indigenous Nigerian medicinal plant used traditionally for treating fever, malarial infection, sexual impotence, gonorrhea, malaria, dysmenorrhea, and abdominal pain. This study investigated the safety profile and antimalarial activity of methanol extract of Fagara zanthoxyloides root-bark on Plasmodium berghei-infected mice. Phytochemical analysis and acute toxicity (LD50) of MEFZRB were determined using standard methods. Thirty-six Swiss mice (28–34 g) were distributed into 6 groups (n = 6). Groups 1 and 2 served as normal and negative control respectively. Group 3 mice were parasitized and treated with 5 mg/kg body weight of Coartem® (positive control). Groups 4–6 were P. berghei infected and orally treated with 200, 400, and 600 mg/kg body weight of MEFZRB respectively for 4 days. P. berghei infection was initiated by an intraperitoneal injection of 0.2 ml parasitized red blood cells. The effect of MEFZRB on percentage parasitemia, hematological indices, antioxidant status, liver and kidney functions, and lipid profile parameters was assessed. The LD50 of MEFZRB was 4073.1 mg/kg b.w. A significant (P < 0.05) decrease in percentage parasitemia of treated groups were observed relative to the negative control. Treatment with MEFZRB led to significant (P < 0.05) increases in packed cell volume, hemoglobin, and red blood cell concentrations, whereas white blood cell count significantly (P < 0.05) decreased relative to the negative control. Similarly MEFZRB significantly (P < 0.05) restored altered antioxidant status, liver enzyme activities, and lipid profile indices of the treated groups following P. berghei-infection in mice, thus, indicating the antimalarial property of MEFZRB.

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Data availability

Christian Chijioke Amah is the curator of the data set, which is available on request.

References

  • Adebayo AH, Yakubu OF, Adegbite OS, Okubena O (2017) Haematopoietic induction and hepatic protective roles of Hepacare® in CCl4-induced hepatic damaged rats. Comp Clin Pathol 26:679–688

    CAS  Google Scholar 

  • Adebayo AH, Yakubu OF, Popoola JO, David LC, Okenze G, Agbafor AG, Okubena O (2018) Evaluation of antimalarial and biochemical profiles of Abaleria in Plasmodium berghei-infected mice. Comp Clin Pathol 18:2780–2788

    Google Scholar 

  • Adefisoye MA, AjibadeAko-Nail K, Adejumoke MB (2012) Phytochemical and antibacterial activity of the extracts of Fagara zanthoxyloides on selected cariogenic and enteric bacterial isolates. J Intercult Ethnopharmacol 1(1):1–6

    Google Scholar 

  • Adegbolagun OM, Olukemi OO (2010) Effect of light irradiation on the antimicrobial activity of Zanthoxylum zanthoxyloides (lam) methanolic extract. Afr J Pharm Pharmacol 4:145–150

    Google Scholar 

  • Adetutu A, Olorunnisola OS, Owoade AO, Adegbola P (2012) Inhibition of in vivo growth of Plasmodium berghei by Launaea taraxacifolia and Amaranthus viridis in mice. Malaria Res Treat 2016:1–16

    Google Scholar 

  • Aebi HE (1983) Catalase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Verlag Chemie, Weinhem, pp 273–286

  • Ajanohoun JE, Ahyi MRA, Ake-Assi L (1993) Traditional pharmacopoeia: contribution to ethnobotanical and floristic studies in Uganda. Lagos: OAU/STRC

  • Albers JJ, Warnic GR, Cheung MC (1978) Qualification of high density lipoproteins. Lipids 13:926–932

    CAS  PubMed  Google Scholar 

  • Allain CC, Poon LS, Chain CSG (1974) Enzymatic determination of total serum cholesterol. Clin Chem 20:470–475

    CAS  PubMed  Google Scholar 

  • Anorue EC, Ekpo DE (2020) Non-oxidative effects of the flavonoid-rich fraction of Lasianthera africana leaves on human haemoglobin. All Life 13(1):658–667. https://doi.org/10.1080/26895293.2020.1846085

  • Bonnett R, Davies JE, Hursthouse MB (1976) Structure of bilirubin. Nature 262:326–328

    CAS  Google Scholar 

  • Breman JG, Alilio MS, Mills A (2004) Conquering the intolerable burden of malaria: what’s new, what’s needed: a summary. Am J Trop Med Hyg 71(2):1–15

    PubMed  Google Scholar 

  • Briggs C, Bain BJ (2017) Basic hematological techniques. In: Dacie JV, Lewis SM (eds) Practical hematology, 12th edn. Elsevier, pp 18–49

  • Burtis CA, Ashwood ER, Bruns DE (2006) Teitz textbook of clinical chemistry and molecular diagnostics, 4th edn. Elsevier Saunders, St. Louis, pp 324–389

    Google Scholar 

  • Cheesbrough M (2006) District laboratory practice in tropical countries. Cambridge University Press, Cambridge, p 62

    Google Scholar 

  • Chinchilla M, Guerrero OM, Abarca G, Barrios M, Castro O (1998) An in vivo model to study the anti-malaria capacity of plant extracts. Rev Biol Trop 46(1):1–7

    Google Scholar 

  • Dacie JV, Lewis SM (2000) Practical haematology, 9th edn. Churchill Livingstone, England, pp 485–489

  • Dacie JV, Lewis SM (2011) Practical haematology, 11th edn. Churchill Livingstone, London, pp 57–67

  • Derrell C (1996) Guide for care and use of laboratory animals. Institute of Laboratory Animal Resources. National Academy Press, Washington DC

    Google Scholar 

  • Ekpo DE, Ekanemesang UM (2016) Antiplasmodial/antimalarial effect of ethanol extracts of leaves of Vernonia amygdalina and Gongronema latifolium on the activity of catalase in Plasmodium berghei-parasitized mice. Int J Biochem Res Rev 10(4):1–9

  • Ekpo DE, Joshua PE, Ogidigo JO, Nwodo OFC (2020) High resolution UPLC-PDA-QTOF-ESI-MS/MS analysis of the flavonoid-rich fraction of Lasianthera africana leaves, and in vivo evaluation of its renal and cardiac function effects. Heliyon 6:e04154. https://doi.org/10.1016/j.heliyon.2020.e04154

    Article  PubMed  PubMed Central  Google Scholar 

  • Elujoba AA, Odeleye OM, Ogunyemi CM (2005) Traditional medicine development for medical and dental primary health care delivery system in Africa. Afr J Complement Altern Med 2(1):46–61

    Google Scholar 

  • Enechi OC, Amah CC, Okagu IU, Ononiwu CP, Azidiegwu VC, Ugwuoke EO, Onoh AP, Ndukwe EE (2019a) Methanol extracts of Fagara zanthoxyloides leaves possess antimalarial effects and normalizes haematological and biochemical status of Plasmodium berghei-passaged mice. Pharm Biol 57(1):577–585. https://doi.org/10.1080/13880209.2019.1656753

  • Enechi OC, Okagu IU, Ndefo JC, Chibuogwu CC, Amah CC, Obinyima AG, Kalu L, Okakpu J, Amoke LN (2019b) Methanol extract of Peltophorum pterocarpum stem bark has antimalarial activity and normalizes biochemical changes induced by Plasmodium berghei infection. Adv Life Sci Tech 73:43–52

    Google Scholar 

  • Esan AJ, Omisakin CT, Titilayo OE, Fasakin KA (2014) Gender difference on stress induced by malaria parasite infection and effect of antimalarial drug on stress index. Am J Biomed Res 2(3):42–46

    Google Scholar 

  • Folasade SI, Olukemi OA, Jones MO (2006) Management of sickle cell anemia in Nigeria with medicinal plants: cationic evaluation of extracts and possible effects on the efficacy. J Biol Sci 6:100–102

    Google Scholar 

  • Gavigan CS, Dalton JP, Bell A (2001) The role of aminopeptidases in haemoglobin degradation in Plasmodium falciparum-infected erythrocytes. Mol Biochem Parasitol 117(1):37–48

    CAS  PubMed  Google Scholar 

  • Harborne JB (1973) Phytochemical methods: a guide to modern techniques of plant analysis. Chapman and Hall Ltd, London, pp 279–281

    Google Scholar 

  • Hayyan M, Hashim MA, AL Nashef IM (2016) Superoxide ion: generation and chemical implications. Chem Rev 116(5):3029–3085

    CAS  PubMed  Google Scholar 

  • Henry JB (1974) Clinical diagnosis and management by laboratory methods, 16th edn. W. B. Saunders, p 263

  • Iwalokun BI, Alibi-Sofunde JA, Odunala T, Magbagbeola OA, Akinwande AI (2006) Hepatoprotective and anti-oxidant activities of Vernonia amygdalina on acetaminophen-induced hepatic damage in mice. J Med Food 9(4):526–530

    Google Scholar 

  • Jendrassik L, Grof P (1938) In vitro determination of total and direct bilirubin. Biochemica 297:81

  • Jeruto P, Mutai C, Catherine L, Ouma G (2011) Phytochemical constituents of some medicinal plants used by the Nandis of South Nandi district, Kenya. J Anim Plant Sci 9:1201–1210

    Google Scholar 

  • Joshua PE, Okoro IJ, Ekpo DE, Okagu IU, Ogugua VN (2020) Methanol extract of Erythrina senegalensis leaves (MEES) ameliorates Plasmodium berghei-ANKA65-parasitised aberrations in mice. Front Life Sci 13:66–77. https://doi.org/10.1080/26895293.2020.1718777

  • Kalra BS, Chawla S, Gupta P, Valecha N (2006) Screening of antimalarial drugs: an overview. Indian J Pharmacol 38(1):5–12

    CAS  Google Scholar 

  • Kamdem SL, Belletti N, Tchoumbougnang F, Essia-Ngang JJ, Montanari C, Tabanelli G, Lanciotti R, Gardini F (2015) Effect of mild heat treatments on the antimicrobial activity of essential oils of Curcuma longa, Xylopia aethiopica, Zanthoxylum xanthoxyloides and Zanthoxylum leprieurii against Salmonella enteritidis. J Essent Oil Res 27:52–60

    Google Scholar 

  • Karim A, Sohail MN, Munir S, Sattar S (2011) Pharmacology and phytochemistry of Pakistani herbs and herbal drugs used for treatment of diabetes. Int J Pharmacol 7:419–439

    Google Scholar 

  • Kassim OO, Loyevsky M, Elliott B, Geall A, Amonoo H, Gordenk VR (2005) Effects of root extracts of Fagara zanthoxyloides on the in vitro growth and stage distribution of Plasmodium falciparum. Antimicrob Agent Chemo 49(1):264–268

    CAS  Google Scholar 

  • King KJ, Wootton IDP (1959) Microanalysis in medical biochemistry. J and A. Churchill Ltd., London, pp 14–18

    Google Scholar 

  • Klein B, Read PA, Babson AL (1960) Rapid method for the quantitative determination of serum alkaline phosphatase. Clin Chem 6(2):269–275

    CAS  PubMed  Google Scholar 

  • Kosh-Komba E, Toumnou LA, Zinga I, Touckia I, Lembo PU, Mukeina G, Semballa S, Yongo OD, Syssa-Magale JL (2017) Phytochemical screening, antifungal and antibacterial effect of Zanthoxylum zanthoxyloides and Zanthoxylum macrophylum used in traditional medicine in Yamboro (Central African Republic). Eur J Med Plants 19(3):1–11

    Google Scholar 

  • Lorke D (1983) Determination of acute toxicity. Arch Toxi 53:275–279

    Google Scholar 

  • Lowry OH, Rosbrough RJ, Farr AL, Randall J (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • Mamta S, Rupinder K, Sunil P (2013) Quantification of withanolide A from Withania somnifera dual, in tropic of himalaya using HPLC with DAD detector. Int J Biol Pharm Res 4(10):702–705

    Google Scholar 

  • Maruna RFL (1958) Colorimetric determination of sodium. Clin Chem 2:581

    Google Scholar 

  • Ochei J, Kolhatkar A (2008) Medical laboratory science theory and practice. McGraw Hill, New York, pp 663–665

    Google Scholar 

  • Ogwal-Okeng WJ, Obua C, Anokbonggo WW (2003) Acute toxicity effects of the methanolic extract of Fagara zanthoxyloides (Lam.) root-bark. Afri Health Sci 3(3):124–126

    Google Scholar 

  • Ojurongbe O, Ojo JA, Adefokun DI, Abiodun OO, Odewale G, Awe EO (2015) In vivo antimalarial activities of Russelia equisetiformis in Plasmodiumberghei infected mice. Ind J Pharm Sci 77(4):504–510

    CAS  Google Scholar 

  • Olakunle O, Mark L, Biaffra E, Andrew C, Amonoo H, Gordeuk V (2005) Effects of root extract of Fagara Zanthoxyloides on the in-vitro growth and stage distribution of Plamodium falciparium. J Antimicro Chemoth 49(1):264–268

    Google Scholar 

  • Patel B, Das S, Prakash R, Yasir M (2010) Natural bioactive compound with anticancer potential. Int J Adv Pharm Sci 1:32–41

    CAS  Google Scholar 

  • Peters W (1975) The chemotherapy of rodent malaria, XXII. The value of drug-resistant strains of P. berghei in screening for blood schizontocidal activity. Ann Trop Med Parasitol 69:155–171

    CAS  PubMed  Google Scholar 

  • Pompella A, Visvikis A, Paolicchi A, Tata V, Casini AF (2003) The changing faces of glutathione, a cellular protagonist. Biochem Pharmacol 66(8):1499–1503

    CAS  PubMed  Google Scholar 

  • Prado S, Michel S, Tillequin F, Koch M, Pffeiffer B, Pierre A, Leonce S, Colson P, Baldeyrou B, Lansiaux A, Bailly C (2004) Synthesis and cytotoxic activity of benzo phenanthrolines analogues of nitidine and fagaronine. Bioorg Med Chem 12:3943–3953

    CAS  PubMed  Google Scholar 

  • Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28:56–63

    CAS  PubMed  Google Scholar 

  • Skeggs LT, Hochstrasser HC (1964) Colorimetric determination of chloride. Clin Chem 10:918–936

    CAS  PubMed  Google Scholar 

  • Somsak V, Borkaew P, Klubsri C, Dondee K, Bootprom P, Saiphet B (2016) Antimalarial properties of aqueous crude extracts of Gynostemma pentaphyllum and Moringa oleifera leaves in combination with artesunate in Plasmodium berghei infected mice. J Trop Med 2016:1–6

    Google Scholar 

  • Stevens LA, Coresh J, Greene T, Levey AS (2006) Assessing kidney function measured and estimated glomerular filtration rate. New Eng J Med 354(23):2473–2483

    CAS  PubMed  Google Scholar 

  • Stooper MC (2015) Electrolytes. William C. Shiel Publication, Mission Viejo (CA), pp 34–50

    Google Scholar 

  • Taiwo O, Xu HX, Lee SF (1999) Antibacterial activities of extracts from Nigerian chewing sticks. Phytother 13(8):675–679

    CAS  Google Scholar 

  • Terri AE, Sesin PG (1958) Colorimetric determination of potassium. Am J Clin Pathol 29:86–90

    Google Scholar 

  • Toth PP, Philip JB, Robert SR, William EB, Chapman MJ, Marina C et al (2013) High-density lipoproteins: a consensus statement from the National Lipid Association. J Clin Lipidol 7:484–525

    PubMed  Google Scholar 

  • Trease GE, Evans WC (1989) Pharmacognosy, 13th edn. Bailliere Tindall Books Publishers, London (UK), pp 1–105

  • Trinder P (1951) Colorimetric determination of sodium. Analyst 76:596–598

    CAS  Google Scholar 

  • Udo IO (2011) Potentials of Zanthoxylum xanthoxyloides Lam. for the control of stored product insect pests. J Stored Prod Postharv Res 2:40–44

    Google Scholar 

  • Ugwu OPC, Nwodo OFC, Joshua PE, Odo CE, Ossai EC (2013) The effect of ethanol leaf extract of Moringa oleifera on the lipid profile of malaria infected mice. Res J Pharm Biol Chemi Sci 4(1):1324–1332

    Google Scholar 

  • Vertuani S, Angusti A, Manfredini S (2004) The antioxidants and pro-antioxidants network: an overview. Curr Pharm Des 10(14):1677–1694

  • Visser BJ, Wieten RW, Nagel I, Grobusch MP (2013) Serum lipids and lipoproteins in malaria-a systematic review and meta-analysis. Malar J 12:442–454

    PubMed  PubMed Central  Google Scholar 

  • Wallin B, Rosengren B, Shertzer HG, Camejo G (1993) Lipoprotein oxidation and measurement of TBARS formation in single micro litre plate; its use for evaluation of antioxidants. Anal Biochem 208:10–15

    CAS  PubMed  Google Scholar 

  • World Health Organization (WHO) (2020) Malaria fact sheet. Available at https://wwwwho.int/en/news-room/fact-sheets/detail/malaria. Accessed April 28 2020

  • Ynalvez RA, Cardenas C, Addo JK, Adukpo GE, Dadson BA, Addo-Mensah A (2012) Evaluation of the antimicrobial activity of Zanthoxylum zanthoxyloides root bark extracts. Res J Med Plants 6(2):149–159

    Google Scholar 

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Acknowledgements

The authors are grateful to the technical staff of the Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, for their technical assistance.

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Authors and Affiliations

  1. Medical and Pharmacological Biochemistry Research Unit, Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Enugu State, 410001, Nigeria

    Christian Chijioke Amah, Osmund Chukwuma Enechi, Daniel Emmanuel Ekpo, Innocent Uzochukwu Okagu, Chidinma Pamela Ononiwu & Parker Elijah Joshua

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  1. Christian Chijioke Amah
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  2. Osmund Chukwuma Enechi
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  3. Daniel Emmanuel Ekpo
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  4. Innocent Uzochukwu Okagu
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Contributions

All authors made significant contributions to the conceptualization and design of the study.

C.C. Amah: Conceptualized and designed the work; acquisition of materials and reagents; conducted laboratory experiments; analyzed and interpreted the data.

O.C. Enechi: Conceptualized and designed the work; supervised the work.

D.E. Ekpo: Analyzed and interpreted the data; acquisition of relevant literatures; wrote the initial and final manuscript versions; coordinated peer review process.

I.U. Okagu: Conceptualized and designed the work; analyzed and interpreted the data.

C.P. Ononiwu: Acquisition of materials and reagents; conducted laboratory experiments.

P.E. Joshua: Conceptualized and designed the work; analyzed and interpreted the data; supervised the work.

All authors commented on previous versions of the manuscript; read; and approved the final manuscript.

Corresponding author

Correspondence to Parker Elijah Joshua.

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All procedures performed involving the use of experimental animals in this study were in accordance with the Institutional Ethics and Biosafety Committee of the Faculty of Biological Sciences, University of Nigeria, Nsukka, Nigeria (Approval No. UNN/FBS/EC/1042), together with the International Guidelines for Handling of Laboratory Animals (Derrell 1996).

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Amah, C.C., Enechi, O.C., Ekpo, D.E. et al. Safety assessment and antimalarial property of methanol extract of Fagara zanthoxyloides root-bark on Plasmodium berghei-infected mice. Comp Clin Pathol 30, 217–228 (2021). https://doi.org/10.1007/s00580-021-03202-7

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