Qinghua Luo, Fang Li, Xu Liu, Tengfeng Yan, Li Yang, Wenping Zhu, Heqing Zheng, Yan Li, Jianglong Tu, Xingen Zhu
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引用次数: 0
Abstract
Background: Chronic cerebral hypoperfusion (CCH) contributes significantly to white matter injury (WMI) and cognitive impairment, often leading to vascular dementia (VaD). Inefficient clearance of myelin debris by microglia impedes white matter repair, making microglia-mediated myelin clearance a promising therapeutic strategy for WMI. Puerarin (Pu), an isoflavonoid monomer from Pueraria lobata, is known for its neuroprotective, anti-inflammatory, and immunoregulatory properties. However, its effects and underlying mechanisms in counteracting CCH-induced damage remain unclear. In this study, we aimed to investigate the therapeutic effects and underlying mechanisms of puerarin in a CCH mouse model.
Methods: Right unilateral common carotid artery occlusion (rUCCAO) was used to model CCH in C57BL/6J mice. Puerarin (400 mg/kg/day) was administered intraperitoneally for 10 consecutive days starting immediately post-surgery. Cognitive function was assessed by the Morris Water Maze (MWM) test. WMI, remyelination, neuroinflammation, and microglial phagocytosis were evaluated by western blotting, immunofluorescence staining, RT-PCR, or flow cytometry both in vivo and in vitro.
Results: Puerarin treatment significantly improved cognitive performance and mitigated WMI in rUCCAO mice. These effects were associated with enhanced microglial phagocytosis and remyelination, reduced neuroinflammation, and increased CD36 expression. Additionally, puerarin also increased the levels of IL-10 and phosphorylated STAT3 (p-STAT3) in brain tissues. Notably, IL-10 neutralization reversed these benefits effects by reducing microglial myelin debris uptake, downregulating STAT3 phosphorylation and CD36 expression.
Conclusions: Our findings demonstrate that puerarin has significant therapeutic potential in treating CCH-related cognitive impairments and WMI by modulating CD36-mediated microglial myelin clearance through the IL-10/STAT3 pathway. However, our study was reliant on preclinical animal models, further studies are needed to explore applicability in human subjects.
期刊介绍：
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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