Phytochemical, Acute Toxicity, and Anti-plasmodial Potential of Concomitant Extracts of Azadirachta indica and Mangifera indica on Liver Function and Microscopic Anatomy in Swiss Mice

Authors

DOI:

https://doi.org/10.4314/ajtmbr.v7i2.2

Keywords:

Azadirachta indica, Mangifera indica, Plasmodium berghei, anti-plasmodial, liver function

Abstract

Introduction: In sub-Saharan Africa, malaria is the predominant contributor to mortality and there is significant dependence on phytotherapy for its treatment. This study investigated comparative phytoconstituents, acute toxicity, anti-plasmodial activities on liver function and microanatomical perturbations following the concomitant administration of ethanol extracts of Azadirachta indica leaves and Mangifera indica bark in Plasmodium berghei-infected Swiss mice.

Materials and Methods: Sixty experimental mice were allotted into 12 groups (n = 5) and inoculated 6 with 1 x 10 P. berghei two weeks post- acclimatization. Group one served as the normal control; group two [parasitized-non-treated] and groups 3 to 11 were low, medium, and high doses of the extracts singly and concomitantly, while group 12 received artemether-lumefantrine. All administrations were via oral route for three days, respectively. Phytochemical screening, parasite density, serum liver enzymes and microanatomical alterations were analyzed.

Results: Phytochemistry showed that A. indica possessed abundant alkaloids that were absent in M. indica. The median lethal dose (LD50) of A. indica leaf and M. indica bark extract was 3240.37 and 2738.61 mg/kg, respectively. The single administration of A. indica outperformed M. indica via mitigated parasite progression, reduced P. berghei-induced hepatotoxicity and elevated liver enzymes.

Conclusion: Azadirachta indica surpasses Mangifera indica in alleviating hyperparasitemia, parasite associated hepatotoxicity, and hepatic microanatomical changes in in vivo rodentia malaria model. A. indica also mild to moderately improved hepatic collagen and glycogen storage than M. indica. It possessed a better synergistic effect than M. indica alone. 

References

WHO (2023). Malaria Fact Sheet. Available at: https://www.who.int/news-room/fact-sheets/detail/malaria, accessed on December 4, 2023.

Xin-zhuan SU, Jian WU, Fangzheng, XU, and Sittiporn P (2022). Genetic mapping of determinants in drug resistance, virulence, disease susceptibility, and interaction of host-rodent malaria parasites. International Journal for Parasitology 91(102637) ISSN 1383-5769.

Talapko J, Škrlec I, Alebić T, Jukić, M, and Včev, A (2019). Malaria: The Past and the Present. Journal of Microorganisms 7(6):179.

Habibi P, Yao Shi Y, GrossideSa MF, and Khan I (2022). Plants as Sources of Natural and Recombinant Antimalaria Agents Molecular Biotechnology 64:1177–1197.

Hawadak J, Foko LP, Pande V, and Singh V (2022). In vitro antiplasmodial activity, hemocompatibility and temporal stability of Azadirachta indica silver nanoparticles. Artificial Cells, Nanomedicine, and Biotechnology 50:1, 286-300.

Abdulai SI, Ishola AA, and Bewaji CO (2023). Antimalarial Activities of a Therapeutic Combination of Azadirachta indica, Mangifera indica and Morinda lucida Leaves: A Molecular View of its Activity on Plasmodium falciparum Proteins. Acta parasitologica, 68(3):659 - 675.

Farahna M, Selma B, Khalid S, Idris M, Pillai K and Khal E (2010). Anti-plasmodial effect of Azadirachta indica in experimental cerebral malaria: apoptosis of cerebellar Purkinje cells of mice as a marker. North American Journal of Medical Sciences 2(11):518-525.

Muema JM, Bargul JL, Obonyo MA, Njeru SN, Matoke-Muhia D, and Mutunga JM (2022). Contemporary exploitation of natural products for arthropod-borne pathogen transmission-blocking interventions. Parasites Vectors 15: 298.

Zivković J, Kumar KA, Rushendran R et al. (2024). Pharmacological properties of mangiferin: bioavailability, mechanisms of action and clinical perspectives. Naunyn-Schmiedeberg's Arch Pharmacol 397:763–781

Zajac D, Stasinska A, Delgado R, and Pokorski M (2013). Mangiferin and its traversal into the brain. Advances in experimental medicine and biology 756:105–111.

Anil KG, and Marcelo JL (2015). Plasmodium sporozoite invasion of the mosquito salivary glands. Current Opinion in Microbiology 12(4): 394-400.

Trivedi, S. and Chakravarty, A. (2022). Neurological Complications of Malaria. Journal of Current Neurology and Neuroscience Reports 22: 499–513.

Harbone TB (1973). Phytochemistry methods: A Guide to Modern Technique of plant Analysis, 3rd Ed. Chapman and Hall, Hong Kong, pp. 120-150.

Soforowa EA (1993). Medicinal plant and traditional medicine in Africa. 2nd ed., Spectrum Books Limited, Ibadan, pp. 152.

National Research Council. Guide for the Care and Use of Laboratory Animals. The National Academies Press, Washington DC 2011; 246p.

Trease GE, and Evans WC (2001). Textbook of Pharmacognosy, 14th Ed, NB Saunders Company Limited, UK. p612.

Tveden-Nyborg P, Bergmann TK, Jessen N, Simonsen U, and Lykkesfeldt J (2023) BCPT 2023 policy for experimental and clinical studies. Basic Clin Pharmacol Toxicol. 133(4):391-396

Lorke D (1983). A New Approach to Practical Acute Toxicity Testing. Arch Toxicol. 54:275 - 287.

Edagha IA, Davies KG, Akpan BC, Mbadugha CC, and Udoiso WU (2014). Ethanolic effect of Emilia sonchifolia leaves possess erythropoietic and hepatoprotective effect in mice infected with Plasmodium berghei berghei. Macedonian Journal of Medical Sciences, 2(1): 11 -17.

WHO (2010). Basic Malaria Microscopy. Part I. Learner’s guide. Second Edition. Pp 1 – 88. ISBN 9789241547826.

Yap CY, and Aw TC (2010). Liver Function Tests (LFTs). Proceedings of Singapore Healthcare. 19(1):80-82.

Dhurba G (2015) Hematoxylin and eosin staining: principle, procedure and interpretation. Histopathology, 4: 125 - 130.

Nema S, Verma K, Mani A, Maurya NS, and Tiwari A, Bharti PK (2022). Identification of Potential Antimalarial Drug Candidates Targeting Falcipain-2 Protein of Malaria Parasite—A Computational Strategy. BioTech 11: 54.

Anis, S. and Singh, K. R. (2023). Evaluation of hypoglycemic activity of bark extracts of Clerodendrum phlomidis. International Journal of Pharmaceutical Research and Applications 8(5):1159 -1172.

Tepongning RN, Mbah JN, Aruolou FL. Fekam. B.F. (2018). Hydrorthanolic extracts of Erigeron floribunous and Azadirachta indica reduced plasmodium berghei parasitemia in Balb/c Mice. Evidence Based Complementary and Alternative Medicine.

Nafiu MO, Adewuyi AI, Abdulsalam TA, and Ashafa AT (2022). Antimalarial activity and biochemical effects of saponin-rich extract of Dianthus basuticus Burtt Davy in Plasmodium berghei-infected mice. Journal of Advances in Traditional Medicine 22: 519 - 529.

Podolak I, Grabowska K, Sobolewska D, Wrobel-Biedrawa D, Makowska-Was J, and Galanty A (2023). Saponins as cytotoxic agents: an update (2010–2021). Part II—Triterpene saponins. Journal of Phytochemistry Reviews 22: 113–167.

Porte S, Joshi V, Shah K, and Chauhan NS (2022). Plants’ Steroidal Saponins - A Review on Its Pharmacology Properties and Analytical Techniques. World Journal of Traditional Chinese Medicine 8(3): 350-385.

Cheenickal M, and Mendez R (2017). Phytochemical screening and the antimicrobial activity of leaves of Azadirachta indica. Juss. International Journal of Scientific & Engineering Research 8(5): 721-724

Achi NK, Onieke D, Ohaeri OC, and Ijeh I (2018). Acute and sub-acute toxicity Evolution of Methanolic leaf extract of Corchorus olitorius in Experimental Animal modes. Asian Journal of Research in Animal and Veterinary Science 1-12

Reddeman R, Glávits R, Endres JR, Clewell AE, Hirka G, Vértesi, A, Béres E, and Szakonyiné IP (2019) A Toxicological Evaluation of Mango Leaf Extract (Mangifera indica) Containing 60% Mangiferin. J Toxicol. 2019:4763015.

Tabuti JR, Obakiro SB, Nabatanzi A, Anywar G, Nambejja C, Mutyaba MR, Omara, T. and Waako, P. (2023). Medicinal plants used for treatment of malaria by indigenous communities of Tororo District, Eastern Uganda. Journal of Tropical Medicine and Health, 51, 34.

Jailoy K, Vannasiri S, Piyabhan P, Lerdvuthisopon N, Boonraeng S, Khonsung P, Lertprasertsuke N, and Sireeratawong S (2013). Acute and subchronic toxicity study of the water extract from the fruits of Piper chaba Hunter in rats. International Journal of Applied Research and Natural Products 3(4): 29 - 35.

Salasanti, C. D., Sukandar, E. Y. and Fidrianny, I. (2014). Acute and subchronic toxicity study of ethanol extract of Anredera cordifolia (Ten.) V. Steenis leaves. International Journal of Pharmacology and Pharmaceutical Science 6(5): 348 - 352.

Farah AO, Nooraain H, Noriham A, Azizah AH, and Nurul HR (2013). Acute and oral subacute toxicity study of ethanolic extract of Cosmos caudatus leaf in Sprague Dawley rats. International Journal of Biosciences, Biochemistry and Bioinformatics 3(4): 301 – 305.

Uraku A (2016). Hepatoprotective effects of Plasmodium berghei infected Swiss mice treated with some plant extracts. Journal of Pharmacy and Allied Health Sciences 6: 1-7.

Ozoko C, Naiho AO, Gbagbeke KO and Odafiagwuna P (2020). Effect of malaria parasitemia and antimalarial/antioxidant treatment on body weight and some reproductive hormones of male mice. Anatomy and Physiology: Current Research 10: 320.

Samuel SA, Ayobami D, and Jane, AE (2018). Comparative effects of commonly used artemisinin-based combination therapies (ACTs) on reproductive parameters in male Wistar rats. MOJ Bioequiv Availab 5: 113 - 119.

Yemitan OK, and Adeyemi OO (2013). Antiepileptogenic and anticonvulsant actions of Dalbergia saxatilis (Hook, F.) in sub-toxic chemical kindling and toxic convulsant models. European Journal of Medicinal Plants 3(2): 288-296.

Ofori-Attah K, Oseni L, Antwi S, and Tandoh MA (2012). A comparative evaluation of in vivo antiplasmodial activity of aqueous leaf extracts of Carica papaya, Azadirachta indica, Mangifera indica and combination there of using Plasmodium infected BALB/C mice. International Journal of Applied Biology and Pharmaceutical Technology 3(3): 372 – 377.

Azizi MA, Nadia NA, Cedric Y, Sidiki N et al (2023). Antimalarial efficacy and antioxidant activity of Lophira lanceolata stem bark ethanol extract using Plasmodium berghei induced-malaria in Swiss albino’s mice. Journal of Parasitology Research Article ID 9400650.

El-Mahmood AM, and Doughari JH (2008). Phytochemical screening and antibacterial evaluation of the leaf and root extracts of Cassia alata Linn. African Journal of Pharmacy and Pharmacology 2(7): 124 -129.

Nnodim JK, Ujowudu CO, Udujih HI, Okone H, Nwobode EI, and Nwadike CN (2012). Hepatocellular enzyme activities and protein level following administration of vitamin during chloroquine induced Hepatotoxicity in Wistar rats. Indian Journal Dev 2(4): 299-302.

Prasad S, Kalra N, and Shukla Y (2007). Hepatoprotective effects of lupeol and mango pulp extract of carcinogen induced alteration in Swiss albino mice. Mol Nutr Food Res. 51:352.

Viriyavejakul P, Khachousaksumet V, and Punsawad C (2014). Liver changes in severe plasmodium falciparum malaria: histopathology, apoptosis, and nuclear factor kappa B expression. Malaria Journal 13: 106.

Kori LD, Valecha N, and Anvikar AR (2018). Insights into the early liver stage biology of Plasmodium. J Vector Borne Dis. 55(1):9-13.

Ilukho FA, Fasipe OJ, and Aigbe FR (2022). Evaluating the hepatoprotective, ameliorative and antioxidant potentials of the crude aqueous leafy extracts of Mangifera indica plant against acute paracetamol-induced hepatotoxicity in a mouse model. Future Science 8(6).

Bharali PJ, Bordoloi SK, Das S, and Lahon K. (2023). Effect of chronic administration of aqueous extract of Neem (Azadirachta indica) leaves on Paracetamol-induced hepatotoxicity in Wistar albino rats. Current Perspectives on Medicinal and Aromatic Plants, 5(2), 146 -161.

Maugeri A, Lombardo GE, and Cirmi S et al (2022). Pharmacology and toxicology of tannins. Arch Toxicol 96:1257–1277.

Lacombe VA, Hinchcliff KW, Geor RJ and Baskin CR (2001). Muscle glycogen depletion and subsequent replenishment affect anaerobic capacity of horses. Journal of Applied Physiology 91(4): 1782-1790

Su D, Zhou T, Wang Y and Wang L (2023). Cold Exposure Regulates Hepatic Glycogen and Lipid Metabolism in Newborn Goats. International Journal of Molecular Sciences. 24(18):14330.

Ravikumar SS, Menaka TR, Vasupradha G, Dhivya K, Dinakaran J. and Saranya V (2019). Cytological intracellular glycogen evaluation using PAS and PAS-D stain to correlate plasma glucose in diabetics. Indian Journal of Dental Research 30(5): 703-707.

Meyerholz DK, Beck, A. P., Gocken, J. A. et al., (2018). Glycogen depletion can increase the specificity of mucin detection in airway tissues. BMC Research 11: 763.

image

Downloads

Published

01/31/2025

How to Cite

1.
Udoh M, Edagha I, Peter A, Udobang J, Udotong I, Ataben M. Phytochemical, Acute Toxicity, and Anti-plasmodial Potential of Concomitant Extracts of Azadirachta indica and Mangifera indica on Liver Function and Microscopic Anatomy in Swiss Mice. AJTMBR [Internet]. 2025 Jan. 31 [cited 2025 Feb. 5];7(2):30-49. Available from: https://ajtmbr.org.ng/index.php/home/article/view/117

Similar Articles

You may also start an advanced similarity search for this article.