Anti-Aging Effect Of Apigenin Through Modulating Mitochondrial Dysfunction, Cellular Senescence, And miR-34a In D-Galactose Induced Brain Aging In Mice

Ayad, Nada Hashem; Awad, Marwa Mahmoud; El-Shaer, Rehab Ahmed; Ibrahim, Hoda Ali Mohammed; Ibrahim, Sarah; AbuoHashish, Norhan Ahmed; Abd El-Khalik, Sarah Ragab

doi:10.21608/ejhm.2025.428202.1850

Anti-Aging Effect Of Apigenin Through Modulating Mitochondrial Dysfunction, Cellular Senescence, And miR-34a In D-Galactose Induced Brain Aging In Mice

Document Type : Original Article

Authors

¹ Medical Biochemistry and Molecular Biology,Faculty of Medicine,Tanta University,Tanta,Egypt

² Physiology Department ,Faculty of Medicine ,Tanta University, Egypt

³ Medical Biochemistry &Molecular Biology Department, Faculty of Medicine, Tanta University, Egypt.

⁴ Human Anatomy& Embryology Department, Faculty of Medicine, Tanta University, Egypt

⁵ Clinical pharmacology Department. Faculty of medicine .tanta university

⁶ Medical Biochemistry & Molecular Biology Department ,Faculty of Medicine ,Tanta University, Egypt

10.21608/ejhm.2025.428202.1850

Abstract

Background: Brain aging is gradual deterioration of brain functions, including cognitive impairment. Apigenin is a natural anti-oxidant. Objective: This study aims to evaluate the anti-aging impact of apigenin on D-galactose-induced brain aging via modulating mitochondrial dysfunction, cellular senescence, redox status and miR-34a.
Materials and methods: Thirty mice were randomly allocated into control group (0.9% saline + dimethyl sulfoxide orally), D-galactose group, D-galactose/apigenin group. D-galactose was subcutaneously injected (150 mg/kg/day). Apigenin was given orally (20 mg/kg/day). All chemicals were administrated for eight weeks. Object location recognition (OLR) test was conducted. Senescence associated β-galactosidase (SA-β-gal) enzyme activity, gene expression, and immunohistochemical expression levels of P16, the super oxide dismutase (SOD) activity, reactive oxygen species (ROS), and malondialdehyde (MDA) levels, gene expression levels of miR-34a, and mitochondrial dynamics markers mitofusin -2 (MFN-2) and fission 1 (Fis-1) were assayed.
Results: The OLR test showed impaired memory in D-galactose group, which was ameliorated by apigenin. D-galactose group showed decreased Fis-1 levels, and SOD activity, and increased activity of SA-β-gal, levels of MFN-2, ROS, MDA, and gene expression of miR-34a and p16. Apigenin administration helped in maintaining mitochondrial homeostasis, increased SOD activities, reduced MDA, ROS levels, SA-β-gal activities and expression levels of miR-34a and p16 in D-galactose/apigenin group. Conclusion: Collectively, apigenin might have anti-aging effect through modulating mitochondrial dysfunction, cellular senescence, redox status, and miR-34a expression.

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