ArticleFrontiers in pharmacology2026
Investigating the therapeutic mechanism of Puerarin in vascular dementia: an integrated approach combining network pharmacology and experimental validation.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- A review of animal models of vascular dementia.Molecular biology reports · 2026Review
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7 authors.
Funding
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Abstract
Background: Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. Puerarin (PUE) is a natural compound isolated from Objective: To investigate the therapeutic effect of Puerarin on VaD and its underlying molecular mechanisms. Materials and Methods: Cognitive performance was assessed using the behavioral testing. Hematoxylin and Eosin staining (H&E) and Nissl staining were employed to assess neuronal morphology in the hippocampus. Additionally, network pharmacology (NP) was used to identify putative bioactive compounds in PUE and candidate targets associated with VaD. Transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), quantitative PCR (qPCR), and Western blotting were used for experimental validation. To further interrogate pathway involvement, lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist, was administered, followed by repeated behavioral testing and molecular analyses. Results: Behavioral testing showed that PUE mitigated two-vessel occlusion (2VO)-induced cognitive deficits and reduced hippocampal neuronal injury. NP identified 17 putative active compounds and 100 overlapping targets between PUE and VaD. GO and KEGG enrichment analyses indicated that these targets were enriched in Toll-like receptor and NF-κB signaling, implicating an anti-neuroinflammatory mechanism. Experimental assays showed that PUE reduced TLR4 and myeloid differentiation primary response 88 (MyD88) expression, decreased nuclear factor-kappa-B p65 (NF-κB p65) phosphorylation, and lowered pro-inflammatory mediator levels. Importantly, the administration of the TLR4 agonist LPS effectively counteracted the therapeutic effects of Puerarin. Conclusion: Puerarin improves learning and cognitive abilities in VaD rats by inhibiting the TLR4/MyD88/NF-κB signaling pathway, thereby attenuating pathological alterations in the hippocampus, protecting the BBB integrity from cerebral ischemic damage, and exerting anti-neuroinflammatory effects.
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