In Vivo Antiplasmodial Activity and Safety Evaluation of the Methanolic Stem-Bark Extract of Artocarpus Heterophyllus in Plasmodium Berghei-Infected Mice
Main Article Content
Abstract
Background: Emergence of antimalarial drug resistance and the limited availability of new agents underscore the need to evaluate traditional medicinal plants as potential sources of novel therapies. Artocarpus heterophyllus stem-bark is used in ethnomedicine for febrile illnesses, but robust in vivo efficacy and safety data are limited. This study evaluated the chemosuppressive antiplasmodial activity and acute oral safety of the methanolic stem-bark extract of A. heterophyllus in a murine malaria model.
Methods: This randomized controlled preclinical experimental study used adult female Swiss albino mice experimentally infected with chloroquine-sensitive Plasmodium berghei. Stem-bark of A. heterophyllus was air-dried, pulverized, and extracted with methanol. Mice were randomly allocated into treatment groups (n = 5 per group) and administered graded oral doses of the extract (25–200 mg/kg) using the standard 4-day suppressive test (Peters’ test). Parasitaemia, and body temperature were recorded. The median effective dose (ED₅₀) was estimated using four-parameter logistic regression. Acute oral toxicity was assessed using the OECD up-and-down/limit test to estimate the median lethal dose (LD₅₀) and therapeutic index.
Results: The extract produced dose-dependent parasitaemia suppression and significantly prolonged survival compared with untreated controls. The highest suppression (63.45%) occurred at 200 mg/kg. The ED₅₀ was 95.85 mg/kg, while the LD₅₀ exceeded 2000 mg/kg, yielding a therapeutic index >21. Mild hepatorenal changes were observed at high exposure on histopathologic examination.
Conclusion: Methanolic stem-bark extract of A. heterophyllus demonstrates significant in vivo antiplasmodial activity with a favourable safety margin in mice, supporting further bioactivity-guided isolation of active compounds and preclinical development.
Downloads
Article Details
Section
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The Journal is owned, published and copyrighted by the Nigerian Medical Association, River state Branch. The copyright of papers published are vested in the journal and the publisher. In line with our open access policy and the Creative Commons Attribution License policy authors are allowed to share their work with an acknowledgement of the work's authorship and initial publication in this journal.
This is an open access journal which means that all content is freely available without charge to the user or his/her institution. Users are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles in this journal without asking prior permission from the publisher or the author.
The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations. While the advice and information in this journal are believed to be true and accurate on the date of its going to press, neither the authors, the editors, nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.
TNHJ also supports open access archiving of articles published in the journal after three months of publication. Authors are permitted and encouraged to post their work online (e.g, in institutional repositories or on their website) within the stated period, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access). All requests for permission for open access archiving outside this period should be sent to the editor via email to editor@tnhjph.com.
How to Cite
References
1.World Health Organization. World malaria report 2023. Geneva: WHO; 2023.
2.Snow RW, Sartorius B, Kyalo D, Maina J, Amratia P, Mundia CW, et al. The prevalence of Plasmodium falciparum in sub-Saharan Africa since 1900. Nature. 2020;550(7677):515–8.
3.White NJ, Pukrittayakamee S, Hien TT, Faiz MA, Mokuolu OA, Dondorp AM. Malaria. Lancet. 2014;383(9918):723–35.
4.Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008;359(24):2619–20.
5.Blasco B, Leroy D, Fidock DA. Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic. Nat Med. 2017;23(8):917–28.
6.Fidock DA, Rosenthal PJ, Croft SL, Brun R, Nwaka S. Antimalarial drug discovery: efficacy models for compound screening. Nat Rev Drug Discov. 2004;3(6):509–20.
7.Willcox ML, Bodeker G, Bourdy G. Traditional medicinal plants and malaria. Boca Raton: CRC Press; 2011.
8.Nguyen PH, Tran MH, Oh SH. Traditional uses and pharmacological properties of Artocarpus heterophyllus: an overview. Asian Pac J Trop Biomed. 2016;6(11):987–94.
9.Ogunlesi M, Adaramoye O, Ogundipe O. Evaluation of antimicrobial and antioxidant properties of Artocarpus heterophyllus. Afr J Tradit Complement Altern Med. 2021;18(5):65–73.
10.Mandal S, Roy A, Das S. Phytochemical and pharmacological overview of Artocarpus heterophyllus Lam. Int J Pharm Sci Rev Res. 2020;62(1):123–30.
11.Chen H, Li X, Zhang Y. Bioactive phenolic constituents of Artocarpus species: chemistry and pharmacology. Phytochem Rev. 2021;20(3):555–75.
12.Ahmad S, Khan MS, Jameel M. Ethnomedicinal and pharmacological potential of Artocarpus species: a review. J Pharm Pharmacol. 2017;69(4):437–52.
13.Peters W, Portus H, Robinson BL. The four-day suppressive in vivo antimalarial test. Ann Trop Med Parasitol. 1975;69(2):155–71.
14.Organisation for Economic Co-operation and Development (OECD). Guideline for testing of chemicals: acute oral toxicity — up-and-down procedure (No. 423). Paris: OECD; 2001.
15.Sofowora A. Medicinal plants and traditional medicine in Africa. 3rd ed. Ibadan: Spectrum Books; 2008.
16.Federal Ministry of Health. National Code of Health Research Ethics. Abuja (Nigeria): National Health Research Ethics Committee of Nigeria; 2014 [cited 2025 Nov 11]. Available from: https://nhrec.net
17.Bancroft JD, Gamble M. Theory and practice of histological techniques. 6th ed. London: Churchill Livingstone; 2008.
18.Bewick V, Cheek L, Ball J. Statistics review 9: one-way ANOVA. Crit Care. 2004;8(2):130–6.
19.Bantie L, Assefa S, Teklehaimanot T, Engidawork E. In vivo antimalarial activity of the crude leaf extract and solvent fractions of Croton macrostachyus Hocsht. (Euphorbiaceae) in mice infected with Plasmodium berghei. BMC Complement Altern Med. 2014;14:79.
20.Munoz V, Sauvain M, Bourdy G, Callapa J, Rojas I, Vargas L, et al. Evaluation of the antimalarial activity of plants used by the Tacana Indians. J Ethnopharmacol. 2000;77(1):91–98.
21.Widyawaruyanti A, Hafid AF, Tumewu L, Febrianty N, Ranggaditya D, Septiani R, et al. Antimalarial activity of crude extracts of Artocarpus heterophyllus, Artocarpus altilis, and Artocarpus camansi. Asian J Pharm Clin Res. 2020;13(1):279–281.
22.Boonlaksiri C, Kamchonwongpaisan S, Tunsuwan K, Kongsaeree P, Kittakoop P, Tanticharoen M, et al. Antimalarial activity of Artocarpus species. Phytochemistry. 2000;54(1):55–58.
23.Hafid AF, Tumewu L, Widyawaruyanti A, Febrianty N, Ranggaditya D, Septiani R, et al. In vitro and in vivo antimalarial activity of Artocarpus species. Asian J Pharm Clin Res. 2016;9(1):279–281.
24.Tumewu L, Hafid AF, Widyawaruyanti A, Febrianty N, Ranggaditya D, Septiani R, et al. Antiplasmodial activity of Artocarpus camansi extract. Asian J Pharm Clin Res. 2021;14(1):279–281.
25.Widyawaruyanti A, Kikuchi M, Murakami A, Kalauni SK, Zaini NC, Syafruddin D, et al. Antimalarial activity of prenylated flavonoids from Artocarpus champeden. Biol Pharm Bull. 2007;30(4):668–670.
26.Aladesanmi A, Odiba O, Odediran S, Oriola A. Antiplasmodial activities of the stem bark extract of Artocarpus altilis Forsberg. Afr J Infect Dis. 2022;16(2S):33–45.
27.Adebajo AC, Odediran SA, Aliyu FA, Nwafor PA, Nwoko NT, Umana US. In vivo antiplasmodial potentials of the combinations of four Nigerian antimalarial plants. Molecules. 2014;19(9):13136-13146.
28.Tumewu L, A’yun LQ, Ilmi H, Hafid AF, Widyawaruyanti A. Artocarpus sericicarpus stem bark contains antimalarial substances against Plasmodium falciparum. J Basic Clin Physiol Pharmacol. 2021;32(4):853-858.
29.Langhorne J, Quin S, Sanni L. Mouse models of blood-stage malaria infections: immune responses and cytokines involved in protection and pathology. Malaria Immunol. 2002;2:204–228.
30.Seiffert E, Jahncke A, Arnold A. Normal temperature range in laboratory mice. J Physiol. 1928;65(3):345–350.
31.Larson WP, Levine M, Bieter R, McLimans W. Study of mouse temperatures, with reference to the effect of temperature on sulfanilamide therapy. J Bact. 1940;39:45.
32.Cordeiro RS, Cunha FQ, Filho JA, Flores CA, Vasconcelos HN, Martins MA, et al. Hypothermia in Plasmodium berghei-infected mice. J Parasitol. 1983;69(1):123–126.
33.Dascombe MJ, Sidara J. The absence of fever in rat malaria is associated with increased turnover of 5-hydroxytryptamine in the brain. In: Milton A, editor. Advances in Pharmacological Sciences: Temperature Regulation. Birkhäuser; 1994. p. 204–228.
34.Oyewo EA, Dascombe MJ. Thermoregulatory responses in Plasmodium berghei-infected rodents. J Physiol. 1986;72(2):145–150.
35.Adepiti AO, Iwalewa EO. Evaluation of antiplasmodial activity and toxicity of Alstonia boonei stem bark extract. J Ethnopharmacol. 2016;183:1–6.
36.Adesida A, Odediran S, Elujoba A, Aladesanmi A, Oriola A, Adeoti R, et al. Correlation of parasitaemia suppression with survival rates in Plasmodium berghei-infected mice. Afr J Biomed Res. 2021;24(1):45–52.
37.Peters W. The chemotherapy of rodent malaria. XXII. The value of mean survival time as an index of drug efficacy. Ann Trop Med Parasitol. 1975;69(2):155–171.
38.Adebajo AC, Odediran SA, Aliyu FA, Nwafor PA, Nwoko NT, Umana US, et al. Evaluation of ethnomedicines for antiplasmodial potentials. J Ethnopharmacol. 2014;153(3):725–732.
39.Odediran S, Ehigie A, Akadiri S, Bamikole R, Adeniyi R, Adeoti R, et al. Combination of ethnomedicines and their effect on survival in malaria-infected mice. Afr J Tradit Complement Altern Med. 2022;19(1):45–52.