Astaxanthin Mitigates Neurocognitive Deficits in D-Galactose-Induced Brain Aging: Targeting HMGB1/TLR4 / NF-κB signaling pathway

Elmorshdy, Shorouk E. M.; Khodir, Suzan A; Abd El-aziz, Noha; lashin, Mohamed E.; Ebeid, Mai A; Nasser, Mai A.; Sharaf, Sabah Mohamed; Al Nabawy, Rania Mohamed; Ali, Radwa Hassan; Khalil, Azza S

doi:10.21608/muj.2025.404087.1236

	Astaxanthin Mitigates Neurocognitive Deficits in D-Galactose-Induced Brain Aging: Targeting HMGB1/TLR4 / NF-κB signaling pathway
Medicine Updates
Articles in Press, Accepted Manuscript, Available Online from 20 August 2025
Document Type: Original Article
DOI: 10.21608/muj.2025.404087.1236
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Authors
Shorouk E. M. Elmorshdy¹; Suzan A Khodir ²; Noha Abd El-aziz³; Mohamed E. lashin⁴; Mai A Ebeid⁵; Mai A. Nasser⁶; Sabah Mohamed Sharaf⁷; Rania Mohamed Al Nabawy⁸; Radwa Hassan Ali⁹; Azza S Khalil¹⁰
¹Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
²Medical Physiology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt.
³Anatomy and Embryology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
⁴Neuropsychiatry Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
⁵Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Egypt.
⁶Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
⁷Pathology Department, Faculty of medicine for Girls, Al-Azhar University
⁸Histology Department, Faculty of Medicine for Girls (Cairo), Al-Azhar University, Cairo, Egypt
⁹Medical Physiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt, Medical Physiology, Faculty of Medicine, Armed Forces College of Medicine (AFCM), Cairo, Egypt
¹⁰Physiology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
Abstract
Introduction: D-galactose (D-gal) caused brain aging and cognitive decline. Astaxanthin (ASX) has anti-inflammatory and antioxidant impacts. Objective: to demonstrate the underlying mechanisms and the neuroprotective impact of ASX in D-gal-induced cognitive impairments Material & methods: Thirty male Wister albino rats were split into three groups: control, D-gal, and D-gal+ASX. Rats were subjected to the NOR and EPM tests, and after they were killed, the hippocampus gene expression of HMGB1, TLR4, NF-kB, and BDNF was evaluated, along with measurements of MDA, SOD, TNF-α, and IL-6. GFAP and NF-kB hippocampus immunoreaction were performed. Results: In contrast to the control group, D-gal had higher hippocampal GFAP and NF-kB immunoreaction and a significantly lower discrimination index of the NOR test, time in the open arms of EPM, SOD, and gene expression of BDNF, D-gal also demonstrated cognitive impairment with significantly higher MDA, TNF-α, IL-6, and hippocampal gene expression of HMGB1, TLR4, and NF-kB. D-gal-induced brain alterations were significantly ameliorated by ASX. Conclusion: By down-regulating the HMGB1/TLR4/NF-kB signaling cascade, improving gliosis, and utilizing neurotrophic, antioxidant, and anti-inflammatory pathways, ASX mitigated D-gal-induced cognitive impairments.
Keywords
Astaxanthin. Aging; BDNF. Cognitive impairment. D-galactose; HMGB1. NF-kB; TLR4


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