Refined qingkailing attenuates reactive astrocytes and glial scar formation after ischemia stroke via the EGFR/PLCγ pathway

• Published in: Phytomedicine (Stuttgart) Vol. 142; p. 156696
• Main Authors: Ren, Zi-Lin, Zhang, Chu-Xin, Zheng, Yu-Xiao, Chen, Cong-Ai, Dan-Chen, Lan, Xin, Yan, Xin, Liu, Ying, He, Yan-Hui, Cheng, Jia-Lin, Han, Jin-Hua, Wang, Qing-Guo, Wang, Xue-Qian, Cheng, Fa-Feng, Li, Chang-Xiang
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.07.2025
• Subjects: Animals; Astrocyte; astrocytes; Astrocytes - drug effects; Astrocytes - metabolism; atrophy; brain; Cells, Cultured; Cicatrix - drug therapy; coculture; Coculture Techniques; Disease Models, Animal; Drugs, Chinese Herbal - pharmacology; EGFR/PLCγ signaling pathway; epidermal growth factor receptors; ErbB Receptors - metabolism; Glial scar; glucose; histopathology; Infarction, Middle Cerebral Artery - drug therapy; ischemia; Ischemic stroke; Ischemic Stroke - drug therapy; Ischemic Stroke - metabolism; Male; microtubules; neurons; Neurons - drug effects; Neuroprotective Agents - pharmacology; oxygen; Rats; Rats, Sprague-Dawley; Refined qingkailing; Signal Transduction - drug effects; stroke; MCAO; IL; EGF; H&E; RQKL; CNS; IS; MCA; Ischemic stroke; Glial scar; Astrocyte; WB; I/R; EGFR; GFAP; SD; Refined qingkailing; TGF; MAP2; OGD/R; p-PLCγ; CSPG; EGFR/PLCγ signaling pathway; ELISA
• ISSN: 0944-7113; 1618-095X; 1618-095X
• DOI: 10.1016/j.phymed.2025.156696

•By interfering with the glial scar's chemical and physical barriers, RQKL lessened neuronal damage.•The EGFR/PLCγ signaling pathway significantly impacts astrocyte activation and glial scar formation after IS.•RQKL influenced neurons by disrupting the EGFR/PLCγ signaling pathway in astrocytes, leading to decreased astrocyte activation and less glial scar formation. Ischemic stroke (IS) is the main cause of disability worldwide, and glial scar can impair neurological recovery during the post-stroke period. Refined qingkailing (RQKL) has been demonstrated to be neuroprotective after IS. The purpose of our study was to investigate the effect of RQKL on glial scar after IS. In this work, rats were used as the model subjects for middle cerebral artery occlusion (MCAO), with 7 and 14 days serving as the critical observational intervals. The treatments of oxygen and glucose deprivation/reoxygenation (OGD/R) were applied to primary astrocytes and an astrocyte-neuron co-culture model. RQKL was effective in improving neurological dysfunction, brain histopathologic manifestations, and reducing the degree of brain atrophy at different stages of glial scar. It also decreased the expression of glial fibrillary acidic protein (GFAP), neurocan, and brevican, and increased the expression of microtubule associated protein 2 (MAP2). In primary astrocyte culture, RQKL reduced the activation and proliferation of astrocytes. In an astrocyte and neuron co-culture model, RQKL decreased the expression of GFAP and brevican in astrocytes, and increased the expression of MAP2 and NF200 in neurons. Epidermal growth factor receptor (EGFR) and p-PLCγ expression was strongly increased following IS, according to both in vivo and in vitro tests, while RQKL decreased EGFR and p-PLCγ expression. When considered collectively, these findings imply that the EGFR/PLCγ signaling pathway is crucial for the activation of astrocytes and the formation of glial scars following IS. Also, RQKL affects neurons by blocking the EGFR/PLCγ signaling pathway on astrocytes, which diminishes the activation of astrocytes and the development of glial scars. [Display omitted]