Frontiers in Pharmacology (Jul 2024)
Brozopine ameliorates cognitive impairment via upregulating Nrf2, antioxidation and anti-inflammation activities
- Zhenzhen Fu,
- Zhenzhen Fu,
- Zhenzhen Fu,
- Xuening Wang,
- Xuening Wang,
- Yanan Fan,
- Yanan Fan,
- Dong Shang,
- Dong Shang,
- Jiahua Zhang,
- Jiahua Zhang,
- Tingting Xiao,
- Tingting Xiao,
- Jiajun Guo,
- Jiajun Guo,
- Yi Wang,
- Yi Wang,
- Zhiyu Wang,
- Zhiyu Wang,
- Zixin Zhang,
- Zixin Zhang,
- Qingran Jia,
- Qingran Jia,
- Jinpeng Zhu,
- Jinpeng Zhu,
- Alireza Behrouznam Jahromi,
- Alireza Behrouznam Jahromi,
- Yinuo Meng,
- Yinuo Meng,
- Na Gao,
- Na Gao,
- Junbiao Chang,
- Yuan Gao,
- Yuan Gao
Affiliations
- Zhenzhen Fu
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Zhenzhen Fu
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Zhenzhen Fu
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Xuening Wang
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Xuening Wang
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Yanan Fan
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Yanan Fan
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Dong Shang
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Dong Shang
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Jiahua Zhang
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Jiahua Zhang
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Tingting Xiao
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Tingting Xiao
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Jiajun Guo
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Jiajun Guo
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Yi Wang
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Yi Wang
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Zhiyu Wang
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Zhiyu Wang
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Zixin Zhang
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Zixin Zhang
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Qingran Jia
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Qingran Jia
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Jinpeng Zhu
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Jinpeng Zhu
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Alireza Behrouznam Jahromi
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Alireza Behrouznam Jahromi
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Yinuo Meng
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Yinuo Meng
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Na Gao
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Na Gao
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- Junbiao Chang
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Yuan Gao
- Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
- Yuan Gao
- School of Basic Medicine, Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, China
- DOI
- https://doi.org/10.3389/fphar.2024.1428455
- Journal volume & issue
-
Vol. 15
Abstract
Oxidative stress and inflammation are crucial factors contributing to the occurrence and development of vascular dementia (VD). In a previous study, we demonstrated that brozopine (BZP) is an anti-ischemic drug. In this study, a model of VD in rats with modified permanent bilateral common carotid artery occlusion (2-VO) was established in vivo, a model of cellular excitotoxicity/oxidative stress was established via L-glutamate-induced PC12 cell injury, a model of neuroinflammation was established in LPS-induced BV2 cells in vitro, and the ameliorative effect of BZP on cognitive impairment was assessed. BZP treatment improved memory deficit in VD rats through inhibiting Ca2+overload and the levels of oxidative stress, ferroptosis, and inflammatory markers (IL-1β, IL-6, and COX-2) in different brain regions. Additionally, we found that the levels of inflammatory markers in the plasma were also reduced in the VD rats. BZP was further found to have antioxidative stress, antiferroptosis (ferroptosis markers: GPX4, P53, and ACSL4), and antineuroinflammatory effects in PC12 and BV2 cells. Its mechanisms of action were found to be related to the activation of the Nrf2/TLR4/NF-κB pathway; the protective effect of BZP was partially inhibited after using Nrf2-specific inhibitors. Thus, BZP has therapeutic properties for the potential mitigation of cognitive impairment.
Keywords
