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Tongqiao huoxue decoction in improving vascular cognitive impairment in rats through PI3K-AKT pathway.

作者信息

Wu Jingwen, Wang Jin, Sun Minjie, Zhang Yuejie, Li Xiang, Xu Ying, Zhu Boran, Gu Xin

机构信息

Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China; School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Nanjing University of Chinese Medicine (Taizhou campus), Taizhou, 225300, China.

出版信息

J Ethnopharmacol. 2025 Sep 25;353(Pt A):120262. doi: 10.1016/j.jep.2025.120262. Epub 2025 Jul 10.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Tongqiao Huoxue Decoction (THD) originated from Yi Lin Gai CuO, which was compiled by Wang Qingren, a famous physician in Qing Dynasty. This prescription is a commonly used prescription for treating blood stasis in the head and orifices. Studies have shown that this prescription can be used to prevent and treat vascular cognitive impairment (VCI). Its neuroprotective properties may be closely related to its ability to regulate inflammation and protect blood vessels, but its mechanism is still unclear.

AIM OF THE STUDY

This study aims to establish a rat model of VCI and explore the therapeutic effect of THD on VCI and its mechanism.

MATERIALS AND METHODS

Transcriptomic profiling was utilized to screen THD-regulated proteins in the hippocampus of vascular cognitive impairment (VCI) rats and predict associated signaling pathways. Spatial learning and memory capacities were evaluated through Morris water maze behavioral testing. Neuronal apoptosis and microglial polarization dynamics were analyzed using multiple histological staining techniques (TUNEL, Nissl). Hippocampal pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IL-18) were quantified via ELISA. Western blot assessed phosphorylation states of PI3K/AKT/mTOR signaling components and CD206 expression.

RESULTS

(1) Behavioral assessments demonstrated THD-mediated enhancement of spatial learning and memory in VCI rats.(2) TUNEL/Nissl staining revealed THD's anti-apoptotic effects on hippocampal neurons in VCI models.(3) Transcriptomic analysis identified shared molecular targets and pathways between THD and VCI pathology.(4) Immunofluorescence co-localization and ELISA confirmed THD's suppression of neuroinflammatory responses in VCI rats.(5) Western blot analysis validated THD's therapeutic modulation of the PI3K-AKT pathway in vascular cognitive impairment.

CONCLUSION

Tongqiao Huoxue Decoction (THD) emerges as a multi-target therapeutic approach for vascular cognitive impairment, exerting neuroprotective effects through PI3K-AKT pathway regulation, attenuation of neuroinflammation, and inhibition of neuronal apoptosis.

摘要

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