Cyclovirobuxine Alkaloid: A Potential Neuroprotective Agent in Scopolamine-induced Anxiety-related Vascular Dementia in Rats-A Review

Abstract: Vascular dementia (VaD) is a progressive neurodegenerative disorder characterized by cognitive decline and anxiety-related symptoms, primarily associated with cerebrovascular dysfunction. Preclinical models frequently employ scopolamine, a muscarinic acetylcholine receptor antagonist, to induce cholinergic deficits and replicate key features of both Alzheimer's disease and VaD. This model reliably demonstrates cognitive impairment, heightened anxiety-like behaviors, and cerebrovascular abnormalities. Recent interest has emerged in Cyclovirobuxine (CVB), a bioactive alkaloid derived from Buxus species, due to its potential neuroprotective properties. CVB exhibits vasodilatory, antiinflammatory, and anti-apoptotic effects, making it a compelling candidate for mitigating neurovascular dysfunction central to VaD pathogenesis. Theoretical frameworks suggest that CVB may counteract scopolamine-induced neurotoxicity by enhancing cerebral perfusion, attenuating oxidative stress, and modulating cholinergic and other neurotransmitter systems. These mechanisms align with established therapeutic targets in VaD, such as neuroinflammation reduction, cholinergic enhancement, and synaptic plasticity modulation. While preclinical evidence supports these roles, the precise molecular pathways and translational relevance of CVB remain insufficiently defined. Rodent models of scopolamineinduced cognitive dysfunction provide a valuable platform for elucidating these mechanisms and assessing the therapeutic potential of CVB and related compounds. Future investigations should focus on delineating the molecular cascades modulated by CVB and evaluating its efficacy in clinically relevant models. Clarifying these pathways may inform the development of targeted interventions for VaD and related neurodegenerative conditions.