Stingless bee honey alleviates cognitive deficits and hippocampal neurodegeneration in an Alzheimer's model: Behavioural, neurochemical, and histological analyses

Shah Rezlan Shajahan; Zaw Myo Hein; Hussin Muhammad; Mohd Zulkifli Mustafa; Yatinesh Kumari; Imrana Jazuli; Azlina Zulkapli; Norshafarina Shari; Che Mohd Nasril Che Mohd Nassir; Muhammad Danial Che Ramli; Shah Rezlan Shajahan; Zaw Myo Hein; Hussin Muhammad; Mohd Zulkifli Mustafa; Yatinesh Kumari; Imrana Jazuli; Azlina Zulkapli; Norshafarina Shari; Che Mohd Nasril Che Mohd Nassir; Muhammad Danial Che Ramli

doi:10.3934/Neuroscience.2026001

AIMS Neuroscience

2026, Volume 13, Issue 1: 1-28. doi: 10.3934/Neuroscience.2026001

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Research article

Stingless bee honey alleviates cognitive deficits and hippocampal neurodegeneration in an Alzheimer's model: Behavioural, neurochemical, and histological analyses

1.
School of Graduate Studies, Postgraduate Centre, Management and Science University, Shah Alam 40100, Selangor, Malaysia
2.
Department of Basic Medical Sciences, College of Medicine, Ajman University, P.O.BOX:346 Ajman, United Arab Emirates
3.
Toxicology & Pharmacology Unit, Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Shah Alam 40170, Selangor, Malaysia
4.
Department of Neuroscience, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150 Kota Bharu, Kelantan, Malaysia
5.
Neurological Disorder & Aging Research Group (NDA), Neuroscience Research Strength (NRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Selangor, Malaysia
6.
Laboratory Animal Resource Unit, Special Resource Centre, Institute for Medical Research, National Institute of Health, Jalan Pahang, 50588 Kuala Lumpur, Malaysia
7.
Department of Anatomy and Physiology, School of Basic Medical Sciences, Faculty of Medicine, University Sultan Zainal Abidin, 20400 Kuala Terengganu, Terengganu, Malaysia
8.
Faculty of Health & Life Sciences, Management & Science University, Shah Alam 40100, Selangor, Malaysia

Received: 08 September 2025 Revised: 04 December 2025 Accepted: 16 December 2025 Published: 16 January 2026

Stingless bee honey (SBH), widely consumed in Southeast Asia, is traditionally valued for its medicinal and nutritional properties, particularly in promoting brain health. However, its neuroprotective potential against Alzheimer's disease (AD) remains underexplored. In this study, we investigated the therapeutic effects and safety of SBH in a rat model of AD. A total of sixty-three adult male Sprague-Dawley rats (180–200 g) were used: Fifteen were assigned to three toxicity groups (500, 750, 1000 mg/kg; n = 5) and forty-eight to six therapeutic groups (n = 8): Normal control, AD (AlCl₃ + D-gal), AD + Donepezil (1.5 mg/kg), and three SBH-treated groups (500, 750, 1000 mg/kg). Alzheimer-like pathology was induced by aluminium chloride (150 mg/kg) and D-galactose (300 mg/kg), followed by 14 days of treatment. Toxicity was evaluated through liver and kidney histopathology, while behavioural performance was assessed using the Open Field Test and Morris Water Maze. Serum dopamine, serotonin, corticosterone, and acetylcholinesterase activity were quantified via ELISA, and hippocampal morphology was examined histologically. SBH administration produced no signs of systemic toxicity and significantly improved exploratory activity and spatial learning, with the most pronounced effects at 750 mg/kg. Biochemical assays showed reduced acetylcholinesterase and corticosterone levels alongside increased dopamine and serotonin concentrations. Histological analysis confirmed neuronal preservation and reduced hippocampal damage. Inclusion of Donepezil as a positive control enabled comparison with a standard pharmacological treatment. These findings demonstrated that SBH is a safe and promising natural therapeutic capable of alleviating cognitive deficits associated with AD.
- Alzheimer's disease,
- stingless bee honey,
- cognitive impairment,
- aluminium chloride,
- D-galactose,
- hippocampus,
- acetylcholinesterase,
- dopamine,
- serotonin,
- corticosterone
Citation: Shah Rezlan Shajahan, Zaw Myo Hein, Hussin Muhammad, Mohd Zulkifli Mustafa, Yatinesh Kumari, Imrana Jazuli, Azlina Zulkapli, Norshafarina Shari, Che Mohd Nasril Che Mohd Nassir, Muhammad Danial Che Ramli. Stingless bee honey alleviates cognitive deficits and hippocampal neurodegeneration in an Alzheimer's model: Behavioural, neurochemical, and histological analyses[J]. AIMS Neuroscience, 2026, 13(1): 1-28. doi: 10.3934/Neuroscience.2026001

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Abstract

Stingless bee honey (SBH), widely consumed in Southeast Asia, is traditionally valued for its medicinal and nutritional properties, particularly in promoting brain health. However, its neuroprotective potential against Alzheimer's disease (AD) remains underexplored. In this study, we investigated the therapeutic effects and safety of SBH in a rat model of AD. A total of sixty-three adult male Sprague-Dawley rats (180–200 g) were used: Fifteen were assigned to three toxicity groups (500, 750, 1000 mg/kg; n = 5) and forty-eight to six therapeutic groups (n = 8): Normal control, AD (AlCl₃ + D-gal), AD + Donepezil (1.5 mg/kg), and three SBH-treated groups (500, 750, 1000 mg/kg). Alzheimer-like pathology was induced by aluminium chloride (150 mg/kg) and D-galactose (300 mg/kg), followed by 14 days of treatment. Toxicity was evaluated through liver and kidney histopathology, while behavioural performance was assessed using the Open Field Test and Morris Water Maze. Serum dopamine, serotonin, corticosterone, and acetylcholinesterase activity were quantified via ELISA, and hippocampal morphology was examined histologically. SBH administration produced no signs of systemic toxicity and significantly improved exploratory activity and spatial learning, with the most pronounced effects at 750 mg/kg. Biochemical assays showed reduced acetylcholinesterase and corticosterone levels alongside increased dopamine and serotonin concentrations. Histological analysis confirmed neuronal preservation and reduced hippocampal damage. Inclusion of Donepezil as a positive control enabled comparison with a standard pharmacological treatment. These findings demonstrated that SBH is a safe and promising natural therapeutic capable of alleviating cognitive deficits associated with AD.

Acknowledgments

The authors would like to thank the Management and Science University (MSU) for providing the instruments and facilities necessary for conducting this research. The authors also express their gratitude to Ajman University, UAE, for the support for the article processing charge (APC). Finally, we appreciate all the authors for their contributions and approval of the final manuscript.

Funding

The authors are grateful for the research grant provided by Management and Science University. Grant ID: SG–020–022023–FHLS

Authors' contributions

Conceptualization: Shah Rezlan Shajahan, Zaw Myo Hein, Muhammad Danial Che Ramli; Investigation: Shah Rezlan Shajahan; Methodology: Shah Rezlan Shajahan, Yatinesh Kumari, Imrana Jazuli; Resources: Hussin Muhammad, Azlina Zulkapli, Mohd Zulkifli Mustafa; Formal analysis: Shah Rezlan Shajahan, Zaw Myo Hein; Software: Shah Rezlan Shajahan, Yatinesh Kumari, Imrana Jazuli; Supervision: Muhammad Danial Che Ramli, Norshafarina Shari, Zaw Myo Hein, Che Mohd Nasril Che Mohd Nassir; Writing-original draft: Shah Rezlan Shajahan; Writing-review & editing: Shah Rezlan Shajahan, Zaw Myo Hein, Muhammad Danial Che Ramli. All authors approved the final version for publication.

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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