1Department of Science Laboratory Technology, Faculty of Pure and Applied Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
2Department of Medical Biochemistry, College of Health Sciences, Faculty of Medical Science University of Ilorin, Ilorin, Nigeria.
3Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo State Nigeria.
4Department of Pharmacology and Therapeutics, College of Health Sciences, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo State Nigeria
Cognitive dysfunction is a phenomenon characterized by impairment in memory, learning and executive function with exposure to environmental toxins like aluminum chloride (AlCl3) being a potential contributing factor. Aluminum chloride-induced cognitive dysfunction is a significant concern as it can lead to neuronal damage and impaired cognitive function. Current pharmacological interventions for managing cognitive dysfunction are often limited by their side effects, limited efficacy and inability to address the underlying causes of cognitive decline, highlighting the need for alternative therapeutic strategies. This study aims to investigate the cognitive properties of coconut oil extract (COE) on aluminum chloride-induced cognitive dysfunction in male albino rats exploring its potential as a natural and effective therapeutic agent in mitigating cognitive decline. Thirty-six male albino rats were randomly divided into six groups of 6 animals each: normal control, AlCl3 group (100 mg/kg bw), AlCl3 (100 mg/kg bw) + donepezil (1 mg/kg bw), AlCl3 (100 mg/kg bw) + COE at 2.5, 5, and 10 ml/kg body weight respectively. The COE was prepared using manually operated mechanical hydraulic press. Cognitive dysfunction was induced by oral administration of AlCl3 (100 mg/kg bw) with concomitant administration of COE for 28 days. The apparatus employed for behavioral assessments included Y-maze for the determination of spatial working memory, grooming and rearing counts. Open field apparatus was used in the determination of locomotor and exploration of familiar and unfamiliar objects as well as line crossing while novel object apparatus was employed for the determination of memory recognition. Data were expressed as mean ± standard error and analyzed using ANOVA and a level of P<0.05 was considered as significant. Result revealed that AlCl3 significantly reduced spontaneous alternation percentage, line crossing, rearing counts, discrimination index, and spatial memory, while grooming counts significantly (p<0.05) increased. COE treatment, particularly at 10 ml/kg bw, improved all parameters in a dose-dependent manner, with effects comparable to donepezil (1 mg/kg bw), a standard drug used for the management of cognitive dysfunction. The observed cognitive property may be related to the presence of medium-chain triglycerides and phenolic compounds in the COE, as well as its antioxidant and anti-inflammatory properties. In conclusion, findings from this study suggest COE offers a potential or alternative therapeutic approach for mitigating aluminum-induced neurotoxicity.
Cognitive dysfunction refers to a decline in cognitive function including impairments in memory, learning, attention and executive function (Harada et al., 2013). It can result from various factors including aging, neurodegenerative diseases, traumatic brain injury and exposure to environmental toxins (Kulkanu and Kaur, 2015). Cognitive dysfunction can have a significant impact on an individual quality of life, daily functioning and overall well-being (Sacdev et al., 2014). The underlying mechanism of cognitive dysfunction involves complex interaction between neurotransmitters, hormones and other signaling molecules (Spiljagic et al., 2022). Oxidative stress, inflammations and neuronal damage are also taught to play a critical role in the development of cognitive dysfunction (Franzoni et al., 2021). Aluminum chloride (AlCl3) has been widely used in animal models to study cognitive dysfunction as it induces oxidative stress, inflammation and neuronal damage leading to impaired cognitive function (Abbas et al., 2022; Wei et al., 2024). Exposure to AlCl3 has been shown to disrupt cognitive function by altering neurotransmitters systems impairing synaptic plasticity and promoting neuronal apoptosis (Kawahara and Kato-Negishi, 2011). Coconut oil derived from the pulp of coconut (Cocos nucifera) has been traditionally used for its medicinal and nutritional properties (Intahphuak et al., 2010). The potential cognitive property of coconut oil has been reported particularly its medium chain triglycerides (MCTs) which are metabolized into ketone bodies for providing an alternative energy source for brain cells (Taylor et al., 2018). The MCTs in coconut oils such as lauric acid, capric acid, and caprylic acid have been reported to possess neuroprotective antioxidants and anti-neuro inflammation properties which may counteract aluminum chloride-induced neurotoxicity (Ramesh et al., 2021; Ooi et al., 2022). Despite the reports on cognitive properties of coconut oil extract, experimental evidence particularly in well-established animal model of aluminum chloride-induced cognitive impairment remain scarce. Therefore, this study aims to investigate the cognitive properties of coconut oil extract in aluminum chloride-induced cognitive dysfunction in male albino rats.
Induction of Cognitive Dysfunction
Aluminum chloride (AlCl3) was used to induce cognitive dysfunction in the experimental rats being a heavy metal that possesses immeasurable neurotoxic properties with ability to impact the brain tissue thereby causing dysfunction in the hippocampus region (Nallagouni et al., 2017). 100 mg/kg of AlCl3 was administered orally with the aid of canula for 28 days according to the method of Shunan et al., (2021).
MATERIALS AND METHODS
Experimental Animal
Thirty-six male albino rats (200-220g) were obtained from the animal house of the Department of Physiology, Ladoke Akintola University of Technology (LAUTECH), Ogbomoso, Nigeria. They were acclimatized for two weeks before the commencement of the experiment, and kept throughout the experiment in a well-ventilated plastic cages (6 rats per cage) in the animal house under controlled environmental conditions (temperature 28 ± 2 °C; photoperiod: 12-h natural light and 12-h dark: relative humidity: 50-55%) with free access to feed and water ad libitum. The animal handling procedure was done according to guidelines for the use of laboratory animals, as recommended by the animal care and use research ethic committee of Ladoke Akintola University of Technology (LAUTECH), Ogbomoso were followed.
Drugs and Reagents
All drugs and reagents used were of high analytical grade. Aluminum chloride (AlCl3) was obtained from (Sigma-Aldrich, USA). Donepezil, a manufactured in St. Louis, MO, USA; with Product No. TN00002269 was purchased from a Pharmacy store around Starlight junction, Ogbomoso, Oyo state Nigeria.
Processing of the Coconut
Fresh mature coconuts (Cocos nucifera L.) were purchased from the open market around Recreational Club, Ogbomoso and authentication was carried out in the herbarium of the Department of Pure and Applied Biology, Faculty of Pure and Applied Sciences, Ladoke Akintola University of Technology Ogbomoso (Voucher Number: LHO 903). The coconut fruits were broken and the hard shells removed, and endosperm subsequently rinsed to remove dirt before being cut into smaller pieces in order to ensure proper drying in the oven set at 40°C. The dried coconut was kept in order to employ hydraulic press for the extraction of oil.
Extraction of Coconut Oil
About 5000g of the dried coconut was pressed through the use of manually operated mechanical hydraulic press. The dried coconut was transferred into a metal chamber built in the hydraulic press with subsequent application of pressure, in order to force the oil out through an outlet and the oil was collected by a previously cleaned and dried container. The extracted oil was transferred to hot-air oven set at 400C for 24 hours, so as to eliminate moisture content from the oil. (Gunstone, 2011). After 24 hours, the coconut oil extract was obtained and subsequently transferred into a clean, dried sample bottle to be later used.
Experimental Design
Thirty-six (36) male albino rats were randomly divided into six (6) groups of (n = 6) animal.
Group 1 - Normal Control: Rats given normal feed and water only.
Group 2 - Negative Control: Rats administered with aluminum chloride orally. (100 mg/kg/ bw).
Group 3 - Positive Control: Rats administered with aluminum chloride (100 mg/kg/ bw) and treated with donepezil (1 mg/kg/ bw).
Group 4 - COE Low Dose: Rats administered with aluminum chloride (100 mg/kg/ bw) and treated with 2.5 ml/kg bw coconut oil extract orally
Group 5 - COE Medium Dose: Rats administered with aluminum chloride (100 mg/kg bw) and treated with 5 ml/kg bw of coconut oil extract orally
Group 6 - COE High dose: Rats administered aluminum chloride (100 mg/kg bw) and treated with 10 ml/kg bw of coconut oil extract orally.
(AlCl3) was administered for 28 consecutive days to induce neurotoxicity. Donepezil and COE were given concomitantly with AlCl3 via oral gavage.
Behavioral Assessment
Behavioral tests were performed 24 h after the last treatment in a quiet, controlled environment between 08:00 and 12:00 h. Rats were habituated to the testing room for 30 min before each assessment.
1. Y-Maze Test
Spontaneous alternation behavior was used to evaluate spatial working memory. The Y-maze apparatus consisted of three arms (40 cm length, 12 cm height, 3 cm width at bottom and 10 cm at top) at 120° angles. Each rat was placed at the end of one arm and allowed to explore freely for 8 minutes (Cleal et al., 2021) (Fig 1). An alternation was defined as consecutive entries into all three arms without repetition. Percentage alternation was calculated as:
% Spontaneous Alternation=Number of alternationTotal arm enteries-2 ×100
2. Open Field Test
Locomotor and exploratory activities were assessed in a square arena (100 × 100 × 40 cm) divided into equal squares. After the animals were placed in the apparatus and allowed to explore the environment for five minutes, grooming counts, line crossings, and rearing counts were recorded (Snyder et al., 2021) (Fig. 2).
3. Novel Object of Recognition (NOR) Test
Recognition memory was assessed in an open field box by placing the animals into the apparatus. The habituation phase test was conducted for 10 minutes in empty arena after the training phase involving two identical objects, and testing phase involving one familiar object replaced with a novel object after 1hour. Exploration time of each object by the animals was recorded, and the discrimination index (DI) was calculated as:
DI=Time exploring novel object-Time exploring familiar object Total exploration time
Statistical Analysis
Data were expressed as mean ± standard error of the mean (SEM). Statistical analyses were performed using GraphPad Prism version 7.0 (GraphPad Software, Inc., USA). One-way analysis of variance (ANOVA) followed by Tukey’s post-hoc test was used to determine statistical significance. p<0.05 was considered statistically significant.
Fig. 1: Y-Maze Apparatus
Fig. 2: Open Field Test Apparatus
RESULTS
Behavioral assessments conducted in this study includes spontaneous alternation, grooming counts, line crossing, rearing counts, discrimination index, and spatial walking memory. The results from the various assessments revealed significant improvements in groups of animals treated with coconut oil extract (2.5, 5 and 10 ml/kg) and donepezil (1 mg/kg) particularly in a dose-dependent manner when compared with the animals induced with aluminum chloride (AlCl3) administration significantly (P≤0.05) decreased spontaneous alternation percentage compared to the COE group.
Percentage Spontaneous Alternation
Aluminum chloride administration significantly (p<0.05) decreased the percentage spontaneous alternation compared to the normal control group. However, the treatment with donepezil, (1 mg/kg bw) significantly elevated the reduced the percentage spontaneous alternation compared with AlCl3 treated group. The COE at 2.5, 5.0 and 10 ml/kg bw respectively significantly increased the percentage spontaneous alternation reduced by AlCl3 with 10 ml/kg bw of COE showing a higher increase in percentage spontaneous alternation than donepezil (Fig. 3).
Grooming Counts
The treatment of animals in group 2 with AlCl3 significantly (p<0.05) increased the grooming counts compared with the normal control group. Donepezil (1 mg/kg bw) and COE at 2.5, 5.0 and 10 ml/kg bw respectively significantly (p<0.05) reduced the grooming counts in a dose dependent manner compared with AlCl3 treated animals in group 2. The grooming counts in animals treated with 10 ml/kg bw COE was significantly reduced than that of the standard drug (donepezil) (Fig. 4)
Line Crossing Frequency and Rearing Counts
AlCl3 significantly (p<0.05) reduced the line crossing frequency and rearing counts compared with the normal control group. Treatment with donepezil (1 mg/kg body weight) significantly increased the line crossing frequency and rearing counts when compared with the aluminum treated animals in group 2. The COE (2.5, 5.0 and 10 ml/kg body weight) respectively increased the line crossing frequency and rearing counts that was decreased by aluminum chloride with 10 ml/kg body weight of COE showing the highest increase in line crossing frequency and rearing counts compared with AlCl3 treated group (Figs. 5and 6).
Discrimination Index and Spatial Walking Memory
Discrimination index and spatial walking memory of animals in group 2 treated with AlCl3 only were significantly (p<0.05) reduced compared with the normal control group. Treatment with donepezil (1 mg/kg body weight) and COE (2.5, 5.0 and 10 ml/kg body weight) significantly restored the discrimination index and spatial walking memory that was reduced by AlCl3 (Figs. 7 and 8)
Fig 3. The effect of Coconut Oil Extract % Spontaneous Alternation (Y-maze) in Aluminum Chloride-Induced Neurotoxicity in Male Albino Rats
a represents significance difference at p<0.05 when compared to normal control
b represents significance difference at p<0.05 when compared to AlCl3
Fig. 4: Effect of COE on Grooming Counts in Aluminum Chloride-Induced
Neurotoxicity in Male Albino Rats
a represents significance difference at p<0.05 when compared to normal control
b represents significance difference at p<0.05 when compared to AlCl3
c represents significance difference at p<0.05 when compared to COE groups 2.5 and 5.0 ml/kg bw.
Fig. 5: Effect of Coconut Oil Extract on Line Crossing Frequency in Aluminum Chloride-Induced Neurotoxicity in Male Albino Rats.
a represents significance difference at p<0.05 when compared to normal control
b represents significance difference at p<0.05 when compared to AlCl3
Fig. 6: Effect of Coconut Oil Extract on Rearing Counts in Aluminum Chloride-Induced Neurotoxicity in Male Albino Rats.
a represents significance at p<0.05 when compared to Normal control
b represents significance at p<0.05 when compared to AlCl3 treated only
Fig. 7: Effect of Coconut Oil Extract on Discrimination Index and in Aluminum Chloride-Induced Neurotoxicity in Male Albino Rats.
a represents significance at p<0.05 when compared to Normal control
b represents significance at p<0.05 when compared to AlCl3 treated only
Fig. 8: Effect of Coconut Oil Extract on Spatial Walking Memory in Aluminum Chloride-Induced Neurotoxicity in Male Albino Rats
a represents significance at p<0.05 when compared to Normal control AlCl3 treated only
b represents significance at p<0.05 when compared to AlCl3 treated only
DISCUSSION
This study investigated the neuroprotective effects of coconut oil extract (COE) against aluminum chloride (AlCl3)-induced cognitive dysfunction and behavioral impairments in albino rats. Across all behavioral paradigms, AlCl3 exposure produced significant deficits, consistent with established models of Alzheimer’s disease pathology (Dey and Singh, 2022). COE administration, particularly at higher doses, attenuated these impairments in a dose-dependent manner, in some instances achieving effects comparable to donepezil, the reference cholinesterase inhibitor (Alsaffar, 2024). Y-Maze Test is a behavioral assay commonly used in neuroscience and psychology to assess spatial working memory and exploratory activity in rodents (typically mice or rats) (Cleal et al., 2021). The Y-maze test has revealed a significant decline in spontaneous alternation percentage in the AlCl3 group indicating impaired spatial working memory regarded as the early-stage Alzheimer’s disease. This aligns with reports that aluminum neurotoxicity disrupts hippocampal synaptic integrity and cholinergic neurotransmission (Mehpara et al., 2021). However, treatment with 10 ml/kg body weight of the COE significantly restored spontaneous alternation which is an indication of an enhanced cognitive flexibility and memory function. This might have also suggested preservation of hippocampal function, likely through antioxidant and anti-inflammatory mechanisms attributed to its medium-chain triglycerides and phenolic compound (Decandia et al., 2023). This visible effect was successfully comparable to the standard drug, donepezil, thereby reinforcing the therapeutic potential of the coconut oil extract. The number of entries, known to be a general locomotor activity, has shown no significant differences across groups, indicating that the improvement in alternation behavior was not due to hyperactivity but rather a genuine cognitive enhancement. Furthermore, AlCl3 exposure led to increased grooming behavior (stress-induced response) indicative of anxiety and decreased exploratory behavior. Open Field Test is a behavioral assessment used to evaluate locomotor activity, exploratory behavior, and anxiety-like responses in laboratory animals, usually rodents (Snyder et al., 2021). In the open field test, AlCl3 exposure markedly reduced in line crossing and rearing counts, indicating decreased exploratory behavior and possible locomotor suppression. Similarly, Kumar and Gil (2006) reported hypo-activity in aluminum models due to oxidative stress and neuro-inflammation in the basal ganglia. All doses of the COE, particularly the 10 ml/kg group, significantly reduced grooming counts and improved line crossing and rearing behaviors. COE reversed these effects, suggesting mitigation of aluminum-induced dopaminergic and motor deficits. Additionally, grooming counts were elevated in the AlCl3 group, which may reflect stress-related or compulsive-like behaviors. The normalization of grooming frequency by COE, especially at 10 ml/kg body weight, supports its anxiolytic and neuro-restorative potential. These findings suggest that oil extract did not only alleviate anxiety-like behaviors but also enhanced motivation and locomotor activity potentially by modulating stress-related neurotransmitter systems or reduction of neuro-inflammation. Novel Object Recognition Test (Discrimination Index and Spatial Memory) is used for the assessment of memory impairment in which the result is consistent with other documented works (Hendrickx, 2022). The consideration of novel object recognition test has shown that AlCl3-administered rat demonstrated significant reduction in both discrimination index and spatial working memory performance suggesting impaired recognition and recall abilities as result in deficit to the prefrontal cortex-hippocampal connectivity. These findings are consistent with amyloidogenic and tau-related changes induced by aluminum exposure (Pan et al., 2021). However, treatment with coconut oil extract across all doses substantially reversed these impairments by restoring recognition memory, suggesting its role in maintaining synaptic plasticity, with the 10 ml/kg dose again producing the most pronounced effect. This may be mediated by ketone body–driven enhancement of mitochondrial function, a mechanism documented for coconut oil supplementation (Morris et al., 2020). The results suggest COE can promote memory retention and cognitive function possibly through the preservation of hippocampal integrity and synaptic plasticity. The results across all behavioral assessments underscore a dose-dependent neuroprotective role of coconut oil extract. Notably, its effect is comparable to that of Donepezil, a widely used acetylcholinesterase inhibitor in Alzheimer’s management. This indicates that the oil may exert cholinergic-modulating effects, in addition to its potential antioxidant and anti-inflammatory properties. Previous studies have highlighted the presence of medium-chain triglycerides and phenolic compounds in coconut products with potential effect that can enhance brain energy metabolism, reduce oxidative stress, and support neuronal survival (Fernando et al., 2015; Rabail et al., 2021). Aluminum chloride is known to induce neurotoxicity via mechanisms involving oxidative stress, neuro-inflammation, and disruption of neurotransmission (Rajendran et al., 2023). The ability of the oil to counter these effects points toward its multifaceted mode of action (Soares et al., 2021). Moreover, the absence of hyperactivity or sedation across treatment groups further supports its safety and targeted effect (Deng et al., 2021). The finding of this study suggest that coconut oil extract has a potential therapeutic effect in reversing or ameliorating cognitive dysfunction induced by aluminum chloride which is consistent with previous research on the cognitive benefits of coconut oil in Alzheimer’s disease (de la Rubia Orti et al., 2020; Ooi et al., 2022). The oil extract ability to mitigate cognitive decline may be attributed to its contents of medium-chain triglycerides (MCTs) particularly lauric acid, caprylic acid, and capric acid (Ooi et al., 2022). These MCTs are metabolized into ketone bodies such as β-hydroxybutyrate (β-HB) and acetoacetate (AcAc) which provide an alternative energy source for brain cells thereby improving cognitive function and slowing disease progression. The MCTs help to reduce β-amyloid accumulation and subsequently mitigating memory decline (Jensen et al., 2016; Taylor et al., 2018). The polyphenolic compounds in coconut oil may also contribute to its neuroprotective effect by regulating oxidative stress and diminishing neuro-inflammation (Intahphuak et al., 2010)
CONCLUSION
In conclusion, this study demonstrated the potential cognitive benefits of coconut oil extract in ameliorating aluminum chloride-induced cognitive dysfunction in male albino rats highlighting the potential of coconut oil extract as a natural and effective therapeutic agent for cognitive dysfunction.
REFERENCE
Akintola Adebola Olayemi, Oyeleye Samson Adesola*, Kehinde Busuyi David, Lawal Onaopepo Abdulwakeel, Azeez Falilat Bolanle, Cognitive Properties of Coconut Oil Extract Against Aluminum Chloride-Induced Neurotoxicity in Albino Rats, Int. J. Sci. R. Tech., 2025, 2 (9), 59-68. https://doi.org/10.5281/zenodo.17090012
10.5281/zenodo.17090012
