# Exploring the neuroprotective mechanism of Tongqiao Huashuan granules in vascular dementia based on PLCγ1/IP3R signaling pathway

## TL;DR

This study explores how Tongqiao Huashuan granules protect against vascular dementia by regulating a key signaling pathway involved in calcium and oxidative stress.

## Contribution

The study reveals a novel neuroprotective mechanism of TQHS granules via modulation of the PLCγ1/IP3R signaling pathway in vascular dementia.

## Key findings

- TQHS granules improved cognitive function and reduced neuronal injury in a rat model of vascular dementia.
- TQHS granules regulated proteins in the PLCγ1/IP3R pathway and reduced intracellular calcium and ROS levels.
- TQHS granules increased PLCγ1, IP3R, and TrkB gene expression in experimental models.

## Abstract

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.

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.

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.

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.