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 PDF (1.08 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/muj.2025.404087.1236 | ||
| 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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