Mechanism of Huangqi Guizhi Wuwu decoction in ameliorating cerebral ischemia injury via the Nrf2/HO-1 pathway
10.11665/j.issn.1000-5048.2025041403
- VernacularTitle:黄芪桂枝五物汤通过Nrf2/HO-1通路改善脑缺血损伤的机制研究
- Author:
Chengyu QIAN
1
;
Linsheng WANG
;
Jing ZHANG
;
Tao WANG
;
Weidong QIAN
Author Information
1. 南京中医药大学武进附属医院内分泌科, 常州 213161;常州市第一人民医院心内科, 常州 213004;中国药科大学多靶标天然药物全国重点实验室新药筛选与药效评价中心, 南京 2100;南京中医药大学武进附属医院心内科, 常州 213161
- Publication Type:Journal Article 期刊文章
- Keywords:
Huangqi Guizhi Wuwu decoction;
cerebral ischemia;
Nrf2/HO-1 pathway;
oxidative stress;
neuroprotection
- From:
Journal of China Pharmaceutical University
2026;57(1):98-107
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to investigate the protective effects of Huangqi Guizhi Wuwu decoction (HGWD) against cerebral ischemic injury and the underlying mechanisms. A middle cerebral artery occlusion (MCAO) model was established in C57BL/6 mice to evaluate the effects of HGWD on neurobehavioral scores, cerebral infarction rate, brain water content, and oxidative stress and inflammatory markers. The mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in brain tissue were assessed. In addition, Nrf2 knockout mice were used to verify the role of Nrf2 in the protective effects of HGWD against MCAO-induced injury. Additionally, an oxygen-glucose deprivation/reperfusion (OGD/R) model in primary neuronal cells was employed to further confirm the pharmacological effects of HGWD in vitro. The results showed that HGWD significantly ameliorated cerebral ischemic injury in MCAO mice, alleviated oxidative stress, suppressed the release of inflammatory factors, and markedly upregulated the expression of Nrf2, HO-1, and Bcl-2 while downregulating Bax expression, with consistent trends being observed at both mRNA and protein levels. The protective effects of HGWD were significantly attenuated in Nrf2 knockout mice, indicating the pivotal role of Nrf2 in HGWD-mediated protection against cerebral ischemic injury. In vitro experiments revealed that HGWD significantly increased neuronal cell viability, reduced lactate dehydrogenase(LDH) leakage, and decreased apoptosis in OGD/R-treated cells, accompanied by upregulation of Nrf2, HO-1, and Bcl-2 and downregulation of Bax. In conclusion, HGWD protects against cerebral ischemic injury by activating the Nrf2/HO-1 pathway to enhance antioxidant capacity and modulating the Bcl-2/Bax signaling pathway to inhibit apoptosis, thereby protecting brain cells from ischemic damage.
