Biology, Medicine, & Natural Product Chemistry ISSN 2089-6514 (paper) Volume 14, Number 2, October 2025 | Pages: 1009-1013 | DOI: 10.14421/biomedich.2025.142.1009-1013 ISSN 2540-9328 (online) Antipyretic Activity of Stembark Extract of Mammea africana in Rats Jude E. Okokon1*, Chinyelu C. Osigwe2, John A Udobang3, Uwaeme Ugonma Florence2 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Uyo, Uyo, Nigeria 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Madonna University, Elele, Rivers State, Nigeria. 3Department of Clinical Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, University of Uyo, Uyo, Nigeria. Corresponding author* judeefiom@yahoo.com Manuscript received: 02 September, 2025. Revision accepted: 27 October, 2025. Published: 30 October, 2025. Abstract Mammea africana Sabine (Guttiferae), is a tree plant whose parts are variously used locally for the treatment of various diseases such as malaria and fever among others. The stembark extract of M. africana (30 -90 mg/kg) was investigated for antipyretic activity in rats using different experimental models; amphetamine, dinitrophenol and yeast-induced pyrexia. The extract exerted prominent inhibition of pyrexia on amphetamine, dinitrophenol and yeast -induced pyrexia. Inhibition was significant (p<0.05–0.001) from 3 to 5 h post- administration of extract and in a dose-dependent fashion. The antipyretic effects of this plant may in part be mediated through the chemical constituents of the plant. The results of this investigation validate the ethnomedical uses of this plant in the treatment of febrile conditions. Keywords: Mammea Africana; Medicinal plant; antipyretic; fever. INTRODUCTION Mammea africana Sabine (Guttiferae) (syn. Ochrocarpus africana Oliv.) (M. africana), widely distributed in tropical Africa, is a tall tree of 50 to 100 feet high whose bark is often yellow with pale scales and resinous yellow sap (Hutchison and Daziel, 1958). The stembark of the plant is traditionally used by the Ibibios, of Niger Delta region of Nigeria, in the treatment of a number of diseases such as malaria related fever, diabetes, microbial infections and mental disorders. Traditionally, the stembark is used also to treat stomach pains, rheumatism pains, scabies, cough and hypertension (Raponda-Walker and Silans, 1961; Adjanohoun et al., 1996). The stembark extract which possesses cytotoxic activity, in vitro (Chapius et al., 1988; Okokon et al., 2012)., has been reported to contain cytotoxic coumarins with anti- microbial activity against Staphylococcus aureus (Ouahouo et al., 2004). Other pharmacological activities reported on the stembark include; anti-plasmodial (Okokon et al., 2006), cardioprotective (Okokon and Antia, 2007), anti-diabetic, hypolipidaemic (Okokon et al., 2007; Tchamadeu et al., 2010), vasorelaxant (Dongmo et al.,2007), anti-hypertensive (Nguelefack- Mbuyo et al., 2008), anti inflammatory, analgesic (Okokon et al., 2009), antioxidant (Nguelefack-Mbuyo et al., 2010), anti-diarrheal, anti-ulcer (Okokon et al., 2010), immunomodulatory, anti-lesihmanial (Okokon et al.,2012), depressant and anti-convulsant (Okokon and Davies, 2014), nephroprotective (Okokon and Bawo, 2014), hepatoprotective (Okokon et al., 2016), genotoxic and cytotoxic (Ebong et al., 2022) activities. Phytochemical study on the stembark reported the presence of 5,-7-dihydroxy-8-(12- methyl-butryl) – 4 –N -pentylcoumarins and mesuxanthone B (Carpenter et al., 1970;1971; Cricton and Waterman, 1978), 4-phenyl and 4- alkylcoumarins (Games, 1972). While alkaloids have been reported to be absent in the entire plant parts (Gartlans et al., 1980). We report in this study the antipyretic activities of the stembark extract. MATERIALS AND METHODS Plants collection The plant materials, Mammea africana (stembark), were collected in Anwa forest in Uruan area, Akwa Ibom State, Nigeria in January 2022. Identification and authentication of the plant was carried out by a taxonomist of Department of Botany and Ecological Studies, University of Uyo, Uyo, Nigeria. Extraction Pieces of the stembark were washed and shade-dried for two weeks. The dried plants’ materials were further chopped into small pieces and reduced to powder using electric grinder. The powdered material (1.5 kg) was macerated for 72 h in 50% ethanol. This was thereafter https://doi.org/10.14421/biomedich.2025.142.1009-1013 1010 Biology, Medicine, & Natural Product Chemistry 14 (2), 2025: 1009-1013 filtered and the liquid filtrate was concentrated and evaporated to dryness in vacuo 40˚C using a rotary evaporator (BuchiLab, Switzerland). The extract was stored in a refrigerator at -4˚C, until used for the proposed experiments. Animals Albino Wistar rats (122-1136 g) of either sex were obtained from the University of Uyo animal house. They were maintained on standard animal pellets and water ad libitum. Permission and approval for animal studies were obtained from the College of Health Sciences Animal Ethics committee, University of Uyo. Evaluation of antipyretic activity of the Mammea africana stembark extract on D-amphetamine-induced pyrexia The albino rats that were used in this experiment were fasted for 24 hours but allowed water ad libitum before the experiment commenced. They were randomized into groups of 5 rats each according to their weights. The initial basal temperatures of the rats were taken after which pyrexia was induced by intraperitoneal administration of amphetamine (5 mg/kg, i.p) to the animals. Pyrexia was allowed to develop within 30 min post administration of amphetamine. At the confirmation of temperature increase of at least 1℃ by monitoring the rectal temperature, the leaf extract was respectively administered to the different groups of rats at 30, 60 and 90 mg/kg orally and aspirin (100 mg/kg) and distilled water (10 mL/kg, orally) were administered respectively to the positive and negative control groups of rats. Rectal temperatures of the animals were monitored at an hour interval for 5 h (Edem et al., 2023). Effect of Mammea africana stembark extract on 2,4- Dinitrophenol (DNP)-induced pyrexia The albino rats that were used in this experiment were fasted for 24 hours but allowed water ad libitum before the experiment commenced. They were randomized into groups of 5 rats each according to their weights. The initial basal temperatures of the rats were taken after which pyrexia was induced by intraperitoneal administration of dinitrophenol (DNP) (10 mg/kg, i.p.) to the animals. Pyrexia was allowed to develop within 30 min post administration of dinitrophenol. At the confirmation of temperature increase of at least 1℃ by monitoring the rectal temperature, the leaf extract was respectively administered to the different groups of rats at 30, 60 and 90 mg/kg orally and aspirin (100 mg/kg) and distilled water (10 mL/kg, orally) were administered respectively to the positive and negative control groups of rats. Rectal temperatures of the animals were monitored at an hour interval for 5 h (Edem et al., 2023). Effect of Mammea africana stembark extract on yeast- induced pyrexia In this experiment, 24 hours fasted adult albino rats of both sexes allowed water ad libitum were randomized into groups of 5 rats each. At zero hour, the basal rectal temperature of the rats were taken using digital clinical thermometer. Thereafter, each animal was administered subcutaneously with 20% W/V aqueous suspension of yeast at a volume of 10 mL/kg (Okokon and Nwafor, 2010; Edem et al., 2023). The temperatures of rats were monitored at one hour post yeast injection. Rats with temperature increase of 1˚C were selected and grouped for the study. The extract understudy was administered orally after the pyrogen at doses of 30, 60 and 90 mg/kg to respective groups of rats. The control group received distilled water (10 ml/kg) and the reference group was administered with ASA (100 mg/kg) both orally. The rectal temperatures of the groups were taken at 1h interval for 5 h. Statistical analysis Data collected were analyzed using one way analysis of variance (ANOVA) followed by Tukey’s multiple comparison post-test (Graph pad prism software Inc. La Jolla, CA, USA). Values were expressed as mean ± SEM and significance relative to control were considered at p˂0.05. RESULTS Effect of stembark extract of Mammea africana on D-amphetamine induced pyrexia The antipyretic effect of the stembark extract on amphetamine- induced pyrexia is shown in Table 1. The stembark extract (30-90 mg/kg), in the presence of amphetamine, demonstrated significant (p<0.05 – 0.001) lowering of body temperatures of the extract- treated rats when compared with the control. These effects were pronounced and sustained from 2- 5 h post treatment with the extract. The body temperature lowering activity of the extract was not comparable to that of the standard drug, ASA,100 mg/kg (Table 1). Effect of ethanol stembark extract of Mammea africana on 2,4-dinitronitrophenol (DNP)-induced pyrexia in rats The stembark extract of M. africana (30-90 mg/kg) demonstrated significant (p<0.05–0.001) dose- dependent lowering of temperature in DNP-induced pyretic rats. The temperature lowering effect was, however, significant (p<0.05–0.001) and sustained from 4 - 5 h in all the extract-treated groups. The effect of the highest dose (90 mg/kg) was strong but not comparable to that of the standard drug, ASA, 100 mg/kg (Table 2). Okokon et al. – Antipyretic Activity of Stembark Extract of Mammea africana in Rats 1011 Effect of stembark extract of M. africana on yeast- induced pyrexia in rats Treatment of rats with yeast-induced elevated body temperature with stembark extract of M. africana (30- 90 mg/kg) caused significant (p<0.05-0.001) lowering of body temperature of rats elevated by the administration of yeast. The standard drug, ASA,100 mg/kg, lowered the temperature significantly(p<0.05) when relative to the control group (Table 3). The activity of the highest dose (90 mg/kg) of the extract was lower compared to that of the standard drug, ASA,100 mg/kg (Table 3) Table 1. Antipyretic effect of Mammea africana stembark extract on D-amphetamine-induced pyrexia. Treatment/ Dose(mg/kg) Time Intervals (hrs) Basal Temp 0 0.5 1.0 2.0 3.0 4.0 5.0 Control 34.60±0.35 35.94±0.13 36.23±0.17 36.61±0.26 36.77±0.15 37.25±0.38 37.20±0.16 37.`5±0.44 Extract 30 34.78±0.68 35.71±0.53 35.63±0.16 35.50±0.14 35.33±0.13a 35.28±0.15b 35.33±0.36a 34.68±0.13a Extract 60 35.33±0.76 36.56±0.15 35.91±0.31 35.44±0.33 35.30±0.16a 35.01±0.60a 35.13±0.29b 34.70±0.26b Extract 90 34.28±0.18 35.42±0.28 35.33±0.18 35.22±0.26 34.90±0.27a 34.65±0.33b 34.30±0.22b 34.23±0.21c ASA 100 35.04±0.11 36.11±0.31 35.50±0.12 35.03±0.14 34.86±0.12a 34.54±0.28c 34.11±0.15c 33.89±0.24c Values are expressed as mean ± SEM. Significance relative to control. ap<0.05; bp<0.01; cp<0.001. n = 6. Table 2. Antipyretic effect of Mammea africana stembark extract on Dinitrophenol-induced pyrexia. Treatment/ Dose(mg/kg) Time Intervals (hrs) Basal Temp 0 0.5 1.0 2.0 3.0 4.0 5.0 Control 34.42±0.34 36.33±0.21 36.46±0.12 36.54±0.18 36.60±0.54 36.48±0.15 36.20±0.25 36.24±0.12 Extract 30 34.16±0.20 36.15±0.16 36.33±0.24 36.29±0.38 35.97±0.20 35.35±0.42 34.50±0.26a 34.05±0.54b Extract 60 34.55±0.12 36.36±0.22 36.25±0.22 36.16±0.17 35.81±0.37 35.23±0.23 34.32±0.24a 33.76±0.16b Extract 90 35.11±0.32 36.86±0.54 36.20±0.18 35.83±0.35 35.31±0.47 34.86±0.31 33.55±0.28c 33.22±0.19c ASA 100 35.16±0.12 36.91±0.20 36.12±0.26 35.65±0.29 35.10±0.15 34.59±0.12a 33.40±0.12c 33.12±0.26c Values are expressed as mean ± SEM. Significance relative to control. ap<0.05; bp<0.01; cp<0.001. n = 6 Table 3. Antipyretic effect of Mammea africana stembark extract on yeast-induced pyrexia. Treatment/ Dose(mg/kg) Time Intervals (hrs) Basal Temp 0 0.5 1.0 2.0 3.0 4.0 5.0 Control 34.38±0.18 35.60±0.21 36.65±0.15 36.85±0.31 37.20±0.19 37.41±0.26 37.76±0.18 37.44±0.16 Extract 30 34.74±0.26 36.02±0.18 36.24±0.20 36.52±0.34 36.26±0.23 36.11±0.25 36.02±0.26 35.92±0.26 Extract 60 35.08±0.15 36.14±0.78 36.30±0.12 36.10±0.43 36.01±0.10 35.91±0.14a 35.65±0.17b 35.21±0.18c Extract 90 35.10±0.22 36.13±0.28 36.20±0.29 36.15±0.22 35.88±0.31a 35.55±0.16a 35.33±0.12b 35.25±0.20c ASA 100 35.20±0.17 36.29±0.18 36.35±0.32 36.10±0.17 35.78±0.25a 35.42±0.26c 35.30±0.14c 35.05±0.26c Values are expressed as mean ± SEM. Significance relative to control. ap<0.05; bp<0.01; cp<0.001. n = 6. DISCUSSION In this study, the stembark extract of M. africana was investigated for anti-pyretic activity using standard experimental models. The extract inhibited significantly amphetamine, dinitrophenol and yeast- induced pyrexia. Amphetamine causes rise in body temperature by acting on the brain, causing the release of biogenic amines from their storage sites in nerve terminals. Thus resulting in elevated level of cAMP and subsequent increased synthesis of prostaglandins from arachidonic acids produced in neurons by receptor- mediated hydrolysis of phospholipids (Westfall and Westfall, 2006). This leads to hyperthermia. Dinitrophenol causes hyperthermia by uncoupling oxidative phosphorylation resulting in the release of calcium from mitochondrial stores and also blocks calcium reuptake. This results in increased level of intracellular calcium, muscle contraction and hyperthermia (Kumar et al., 2002). Yeast induces hyperthermia by stimulating the synthesis of prostaglandins (Al-Ghamdi, 2001), in the hypothalamus. The extract may have reduced pyrexia by reducing brain concentration of prostaglandin E2 especially in the hypothalamus through its action on COX-2 or by enhancement of the production of the body’s own antipyretic substances such as vasopressin and arginine (Chandrasekharan, 2002). The hypothermic activity of the extract could have also been mediated by vasodilatation of superficial blood vessels leading to increased dissipation of heat following resetting of hypothalamic temperature control center (Rang et al., 2007). This action may be 1012 Biology, Medicine, & Natural Product Chemistry 14 (2), 2025: 1009-1013 due to the phytochemical compounds in this plant. Therefore, the temperature lowering activity of the extract may not be unconnected with the inhibition of one or combination of the above-mentioned mechanisms. The phytochemical compounds in this plant may in part be responsible for the observed antipyretic activities of the stembark extract. 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