An integrated strategy including chemical profiling, network pharmacology and experimental evaluation was used to investigate the effects of Rubia yunnanensis water decoction on vascular dementia.

Abstract

BACKGROUND: Vascular dementia (VaD) is the second most prevalent cause of dementia following Alzheimer's disease. Rubia yunnanensis, a medicinal plant recorded in the Chinese Materia Medica, has historically been utilized for managing cerebral ischaemia-related disorders. While recent attention has focused on its neuroprotective potential, the specific mechanisms underlying the effects of Rubia yunnanensis water decoction (RY-W) on VaD remain unelucidated. OBJECTIVES: This study aimed to identify the active chemical components and elucidate the molecular mechanisms of RY-W in the treatment of VaD by integrating network pharmacology with experimental validation. METHODS: The chemical constituents of RY-W and their potential therapeutic targets were analyzed using UPLC-MS/MS and network pharmacology techniques. To validate these findings, the cerebral protective effects of RY-W were assessed in a rat model of VaD. Cognitive function was evaluated using the Morris Water Maze (MWM) test. Pathological changes and molecular markers were analyzed via Hematoxylin and Eosin (HE) staining, Nissl staining, TUNEL fluorescence staining, Immunohistochemistry (IHC), and Western blotting. RESULTS: Network pharmacology analysis identified IL-6, IL-1β, ALB, TNF, and AKT1 as potential core targets for RY-W. Experimental results demonstrated that RY-W significantly alleviated cognitive deficits in VaD rats. Furthermore, RY-W exhibited anti-inflammatory properties and reduced neuronal apoptosis. These neuroprotective effects appear to be mediated through the regulation of ALB and the PI3K-Akt signaling pathway. CONCLUSION: RY-W effectively ameliorates VaD pathology by exerting anti-inflammatory and anti-apoptotic effects. These findings highlight the involvement of ALB and the PI3K-Akt signaling pathway in the therapeutic action of RY-W, supporting its potential as a treatment for vascular dementia.