Chatterjee Kaberi, Mazumder Papiya Mitra, Banerjee Sugato
Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Kolkata, India.
Eur J Pharmacol. 2025 Mar 5;990:177277. doi: 10.1016/j.ejphar.2025.177277. Epub 2025 Jan 19.
Ageing is a complex process characterized by the gradual deterioration of physiological functions, often leading to a diminished quality of life. Dementia is among the prominent indicators of ageing characterized by cognitive impairment. Animal studies employing D-galactose have provided insights into the mechanisms underlying cognitive decline and neuronal degeneration, resembling features of human brain ageing while Vitamin K2, known for its diverse physiological functions, also have neuroprotective potential. Here we study the effect of Vitamin K2 in D-galactose induced ageing in mice.
Ageing was induced in adult Swiss albino mice using D-galactose via subcutaneous (SC) route for 45 days while one group of animals received Vitamin K2 (MK-7) via oral gavage during last 21 days. Then different behavioral studies, including the elevated plus maze, Morris water maze, passive avoidance and novel object recognition test were performed to measure cognitive changes, followed by measuring AChE, corticosterone (plasma), oxidative stress parameters (SOD, GSH, MDA) and pro-inflammatory markers (TNFα, IL1β) in hippocampal homogenates. Histopathology of the hippocampal sections were performed to measure neuronal density.
Vitamin K2, treatment reversed D-galactose associated memory changes. In the biochemical studies, plasma corticosterone was reduced while hippocampal AChE, MDA and pro-inflammatory cytokines were reduced after Vitamin K2 treatment. The antioxidants like SOD and GSH were improved in Vitamin K2 treated animal brain. The hippocampal neuronal density increased in treatment group compared to D-galactose induced aged animals.
Treatment with Vitamin K2 (MK-7) partially reversed cognitive decline associated with ageing, highlighting its potential as a therapeutic intervention for age associated cognitive decline.
衰老为一个复杂的过程，其特征为生理功能逐渐衰退，常导致生活质量下降。痴呆是衰老的主要指标之一，其特征为认知障碍。使用D-半乳糖进行的动物研究为认知衰退和神经元变性的潜在机制提供了见解，这些特征类似于人类大脑衰老，而维生素K2因其多种生理功能而闻名，也具有神经保护潜力。在此，我们研究维生素K2对D-半乳糖诱导的小鼠衰老的影响。
通过皮下（SC）途径使用D-半乳糖在成年瑞士白化小鼠中诱导衰老45天，而一组动物在最后21天通过灌胃接受维生素K2（MK-7）。然后进行不同的行为学研究，包括高架十字迷宫、莫里斯水迷宫、被动回避和新物体识别测试，以测量认知变化，随后测量海马匀浆中的乙酰胆碱酯酶、皮质酮（血浆）、氧化应激参数（超氧化物歧化酶、谷胱甘肽、丙二醛）和促炎标志物（肿瘤坏死因子α、白细胞介素1β）。对海马切片进行组织病理学检查以测量神经元密度。
维生素K2治疗逆转了与D-半乳糖相关的记忆变化。在生化研究中，维生素K2治疗后血浆皮质酮降低，而海马乙酰胆碱酯酶、丙二醛和促炎细胞因子减少。维生素K2处理的动物脑中抗氧化剂如超氧化物歧化酶和谷胱甘肽得到改善。与D-半乳糖诱导的衰老动物相比，治疗组海马神经元密度增加。
维生素K2（MK-7）治疗部分逆转了与衰老相关的认知衰退，突出了其作为与年龄相关认知衰退治疗干预措施的潜力。
