Albiflorin Alleviates Neurocognitive Impairment in L-Methionine-Induced Vascular Dementia through FoxO1/SIRT1/RANKL/BDNF Pathway

Abstract

Objectives: To assess the possible neuroprotective impacts of albiflorin (ALB) on VaD induced by L-methionine (L-MET) and elucidate the potential underlying mechanisms responsible for these effects.Background: Vascular dementia (VaD) has the second highest prevalence rate after Alzheimer’s disease. Inflammation, endothelial dysfunction, and oxidative stress are critical factors in the pathogenesis of vasodilatory disease.Methods: A total of 30 male albino rats were separated into three groups, each involving 10 rats: Control, VaD, and VaD+ALB groups. Following the trial, the researchers assessed the rats’ cognitive function and measured many factors, including homocysteine (Hcy), superoxide dismutase (SOD), lipid profile (triglyceride levels and total cholesterol), IL-10, malondialdehyde (MDA), and TNF-α. Furthermore, the levels of forkhead box protein O1 (FoxO1), brain-derived neurotropic factor (BDNF), receptor activator of nuclear factor kappa B ligand (RANKL), and SIRT1 were evaluated using real-time PCR. The histological and immunohistochemical research of the thoracic aorta and left cerebral hemisphere involved examining eNOS, GFAB, and Bax immunoreactivity.Results: The study revealed that L-MET administration led to the impairment of cognitive performance, a significant increase in Hcy, MDA, TNF-α, and lipid profile, and a decrease in SOD and IL-10. Moreover, it resulted in downregulating hippocampal FoxO1, SIRT1, BDNF, and eNOS immunoreaction, along with the upregulation of the RANKL gene expression and GFAB and Bax immunoreaction. ALB administration reversed the changes induced by L-MET. Conclusion: ALB ameliorated cognitive impairment and endothelial dysfunction in VaD via its antioxidant, anti-inflammatory, and antiapoptotic effects and improved neurogenesis and gliosis via modulating the FoxO1/SIRT1/RANKL/BDNF signaling pathway.