Apigenin mitigates oxidative stress, neuroinflammation, and cognitive impairment but enhances learning and memory in aluminum chloride-induced neurotoxicity in rats

Ademola Adetokunbo Oyagbemi; Omowumi Moromoke Femi-Akinlosotu; Adedunsola Adewunmi Obasa; Moses Semilore Ojo; Adeola Temitope Salami; Temitayo Olabisi Ajibade; Charles Etang Onukak; Olumayowa Olawumi Igado; Oluwaseun Olarenwaju Esan; Taiwo Olaide Oyagbemi; Adewumi Victoria Adeogun; Omolola Victoria Awoyomi; Joseph E Ikokide; Ishmael Festus Jaja; Olufunke Eunice Ola-Davies; Temidayo Olutayo Omobowale; Adebowale Bernard Saba; Oluwafemi Omoniyi Oguntibeju; Evaristus Nwulia; Momoh Audu Yakubu

doi:10.1002/alz.70223

Apigenin mitigates oxidative stress, neuroinflammation, and cognitive impairment but enhances learning and memory in aluminum chloride-induced neurotoxicity in rats

Alzheimers Dement. 2025 May;21(5):e70223. doi: 10.1002/alz.70223.

Authors

Ademola Adetokunbo Oyagbemi¹, Omowumi Moromoke Femi-Akinlosotu², Adedunsola Adewunmi Obasa³, Moses Semilore Ojo¹, Adeola Temitope Salami⁴, Temitayo Olabisi Ajibade¹, Charles Etang Onukak¹, Olumayowa Olawumi Igado³, Oluwaseun Olarenwaju Esan⁵, Taiwo Olaide Oyagbemi⁶, Adewumi Victoria Adeogun¹, Omolola Victoria Awoyomi⁶, Joseph E Ikokide⁷, Ishmael Festus Jaja^{8

9}, Olufunke Eunice Ola-Davies¹, Temidayo Olutayo Omobowale⁵, Adebowale Bernard Saba¹⁰, Oluwafemi Omoniyi Oguntibeju¹¹, Evaristus Nwulia¹², Momoh Audu Yakubu¹³

Affiliations

¹ Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria.
² Developmental Neurobiology and Forensic Anatomy Unit, Department of Anatomy, College of Medicine, University of Ibadan, Ibadan, Nigeria.
³ Neuroscience Unit, Department of Veterinary Anatomy, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria.
⁴ Development of Physiology, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
⁵ Department of Veterinary Medicine, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria.
⁶ Federal College of Animal Health and Production Technology, Ibadan, Nigeria.
⁷ Department of Theriogenology, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria.
⁸ Department of Livestock and Pasture Science, Faculty of Science and Agriculture, University of Fort Hare, Alice, South Africa.
⁹ Department of Agriculture and Animal Health, University of South Africa, Roodepoort, Johannesburg, South Africa.
¹⁰ Department of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria.
¹¹ Phytomedicine and Phytochemistry Group, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Bellville, South Africa.
¹² College of Medicine, Department of Psychiatry and Behavioral Sciences, Howard University Hospital, Howard University, Washington, District of Columbia, USA.
¹³ Department of Environmental & Interdisciplinary Sciences, College of Science, Engineering & Technology, Vascular Biology Unit, Center for Cardiovascular Diseases, COPHS, Texas Southern University, Houston, Texas, USA.

Abstract

Introduction: Aluminum chloride (AlCl₃) exposure has been linked to neurotoxicity in various animal models, presenting significant concern to human health due to its potential implications in neurodegenerative diseases. Aluminum chloride is a widely recognized neurotoxin and has been used as an animal model of Alzheimer's disease via mechanisms linked with oxidative stress and inflammation. The study investigated the potential ameliorative effect of apigenin on AlCl₃-induced neurotoxicity in rats.

Methods: Forty adult male Wistar rats were randomly divided into four different groups - control, AlCl₃ (100 mg/kg), apigenin (50 mg/kg) plus AlCl₃, and apigenin (50 mg/kg) alone administered orally for 14 days.

Results: Our findings revealed AlCl₃ exposure induced significant neurobehavioral deficits, oxidative stress, neuroinflammation, and loss of the Purkinje cell layer of the cerebellum. Treatment with apigenin attenuated neuroinflammation and enhanced learning and memory with significant improvement in recognition index.

Discussion: Apigenin demonstrates promising ameliorative effects against AlCl₃-induced neurotoxicity in rats.

Highlights: Aluminum chloride toxicity caused significant reduction in learning, exploration, and memory. Aluminum chloride toxicity induced neurotoxicity, increased biomarkers of oxidative stress, neuroinflammation, and precipitated cognitive impairment. Apigenin improved brain antioxidant, enhanced learning, exploration, and memory.

Keywords: Apigenin; cognitive impairment; neurotoxicity; oxidative stress.

MeSH terms

Aluminum Chloride* / toxicity
Aluminum Compounds / toxicity
Animals
Antioxidants / pharmacology
Apigenin* / pharmacology
Chlorides / toxicity
Cognitive Dysfunction* / chemically induced
Cognitive Dysfunction* / drug therapy
Disease Models, Animal
Learning* / drug effects
Male
Maze Learning / drug effects
Memory* / drug effects
Neuroinflammatory Diseases* / chemically induced
Neuroinflammatory Diseases* / drug therapy
Neurotoxicity Syndromes* / drug therapy
Oxidative Stress* / drug effects
Rats
Rats, Wistar

Substances

Apigenin
Aluminum Chloride
Antioxidants
Aluminum Compounds
Chlorides