ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Exploring the neuroprotective mechanism of Tongqiao Huashuan granules in vascular dementia based on PLCγ1/IP3R signaling pathway
Xianhui Huang 1
Jiajia Liu 1
Yanna Ren 1
Dingding Liu 1
Jing Cai 2
Liping Cao 2
Lei Tong 3
Yuanhua Wu 4
1. Guizhou University of Traditional Chinese Medicine, Guiyang, China
2. First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
3. China Academy of Chinese Medical Sciences Institute of Basic Theory of Traditional Chinese Medicine, Beijing, China
4. The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, China
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Abstract
Introduction: Vascular dementia (VaD) is closely associated with oxidative stress and intracellular calcium overload. PLCγ1, IP3R, CAMKKII, and CaM proteins play important roles in mediating intracellular calcium overload and excessive accumulation of reactive oxygen species (ROS). Tongqiao Huashuan (TQHS) granules represent a formulated preparation derived from traditional Chinese medicine (TCM), which have demonstrated extensive clinical application in managing VaD. Although TQHS granules have shown favorable clinical efficacy, the underlying mechanisms remain unclear. The present investigation sought to clarify protective roles exerted by TQHS granules against VaD via modulation of relevant signaling cascades. Methods: Using a permanent bilateral common carotid artery occlusion (2-VO) rat model and an OGD/R-induced SH-SY5Y cell model, we evaluated cognitive function, neuronal injury, and pathway-related molecular changes. Results: TQHS granules markedly ameliorated behavioral deficits and restored cognitive performance in VaD rats following treatment. Immunohistochemistry and Western blotting experiments demonstrated that TQHS granules regulated protein abundance of PLCγ1, p-PLCγ1, IP3R, CAMKKII, and CaM, which are proteins related to the PLCγ1/IP3R signaling pathway, in vivo. Data derived from CCK-8, microplate reader detection, and immunofluorescence experiments demonstrated that TQHS granules increased cell survival rate, reduced intracellular Ca2+ concentration, and reduced ROS levels. RT-qPCR showed that TQHS granules increased the expression of PLCγ1, IP3R and TrkB. Discussion: The neuroprotective effect of TQHS granules on experimental VaD may be mediated by regulating the PLCγ1/IP3R pathway, improving oxidative stress injury and intracellular calcium overload in VaD. TQHS granules hold considerable promise as a viable complementary intervention capable of retarding the neurodegenerative trajectory of VaD.
Summary
Keywords
Intracellular calcium overload, Oxidative Stress, PLCγ1/IP3R signaling pathway, TQHS granules, Vascular Dementia
Received
06 October 2025
Accepted
18 February 2026
Copyright
© 2026 Huang, Liu, Ren, Liu, Cai, Cao, Tong and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Lei Tong; Yuanhua Wu
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