Vitamin K2 (MK-7) modulated Nrf2/NLRP3/caspase-1 axis to protect against age-related structural and cognitive deterioration in naturally aged rats.

Ageing process is accompanied by disrupted maintenance of tissue homeostasis. Declined cognitive function is a hallmark of ageing process. Patients with severe dementia and elderly people at an early stage of Alzheimer's disease demonstrated marked reduction in serum concentration of vitamin K. Menaquinone-7 (MK-7) is a major form of vitamin K2 that can be found in animal products and fermented food. The present study aimed to evaluate the potential protective effect of MK-7 against cognitive decline and structural alterations in brain tissue of naturally aged rats and to delineate the potential involved molecular mechanisms. Three months-aged albino rats were randomly assigned into two groups; ageing control receiving vehicle and ageing group received MK-7 (30 mg/kg, oral, once daily 5 days per week). Treatment was continued for 17 months. Additional group containing three-month-old rats was used as adult control. Modified T-maze, Crawley's sociability test and modified forced swim test were used to assess cognitive level, anxious and depressive like behaviour, respectively. Dissected brain tissues were used to assess neuroprotective mechanisms of MK-7 by histopathology and immunohistochemistry, real time polymerase chain reaction, spectrophotometry and Enzyme-Linked Immunosorbent assay. Behavioural tests showed attenuated cognitive impairment, depression and anxiety and improved spatial memory and learning ability by MK-7 administration. Additionally, brain expression of NLRP3 inflammasome components (NLRP3, caspase-1) and production of downstream inflammatory factors (IL-1β, IL-6 and TNF-α) were markedly decreased in MK-7 treated rats. Further, MK-7 triggered Nrf-2 expression, reduced lipid peroxidation and restored antioxidant enzymes levels. Also, MK-7 dampened microglial activation, modulated hippocampal and cerebral cortical structure alterations and restored tyrosine expression in aged brain. Our findings highlighted MK-7 as a promising candidate for halting progression of structural and cognitive deterioration in aged population. Activation of Nrf-2 accompanied by NLRP3/ caspase-1 suppression participated in neuroprotective effect of MK-7 in rat aged brain.