Cepharanthine hydrochloride alleviates herpesvirus encephalitis by inhibiting Nrf2 degradation

Qiongzhen Zeng; Weixiangmin Zou; Jiaqi Wu; Menghe Li; Zexu Wang; Caiwenjie La; Cuifang Ye; Zhe Ren; Yifei Wang; Kai Zheng

doi:10.1016/j.virs.2026.03.016

April 2026

. doi: 10.1016/j.virs.2026.03.016

Citation: Qiongzhen Zeng, Weixiangmin Zou, Jiaqi Wu, Menghe Li, Zexu Wang, Caiwenjie La, Cuifang Ye, Zhe Ren, Yifei Wang, Kai Zheng. Cepharanthine hydrochloride alleviates herpesvirus encephalitis by inhibiting Nrf2 degradation .VIROLOGICA SINICA, 2026, 41(2) : 392-403. http://dx.doi.org/10.1016/j.virs.2026.03.016

盐酸千金藤碱通过抑制Nrf2降解缓解疱疹病毒性脑炎

曾琼祯 ^a,b ,
邹魏湘闽 ^a,c ,
吴嘉琪 ^a,c ,
李梦鹤 ^a,c ,
王泽旭 ^a,c ,
喇才雯婕 ^a,c ,
叶翠芳 ^a ,
任哲 ^a,c,, ,
王一飞 ^a,c,, ,
郑楷 ^d,,

a 中国广东省广州市, 暨南大学生命科学技术学院细胞生物学系, 邮编 510632;
b 中国广东省深圳市, 广东省老年医学临床研究中心/深圳市老年医学临床研究中心/深圳市人民医院(暨南大学第二临床医学院/南方科技大学第一附属医院), 邮编 518020;
c 中国广东省广州市, 暨南大学生物医学研究所, 广东省生物工程医学重点实验室, 化妆品及天然产物原料创新技术研究重点实验室, 邮编 510632;
d 中国广东省深圳市, 深圳大学医学部药学院, 深圳大学, 邮6 32b中国广

通讯作者： 任哲, rz62@163.com; 王一飞, twang-yf@163.com; 郑楷, zhengk@szu.edu.cn
收稿日期： 2025-10-09
录用日期： 2026-03-30

摘要

I型单纯疱疹病毒（HSV-1）感染可诱发单纯疱疹性脑炎（HSE），这是一种危及生命的神经系统疾病，其特征为病毒在中枢神经系统内活跃复制，并伴随过度的神经炎症反应。盐酸千金藤素（CH）是一种天然的双苄基异喹啉类生物碱，具有多种药理活性。本研究评估了CH对HSV-1感染的抗病毒及抗炎作用。在小胶质细胞中，CH可显著抑制病毒复制，并抑制STING-NF-κB信号通路，从而减轻HSV-1相关的神经炎症。在HSV-1感染过程中，CH可与Nrf2结合，破坏Keap1-Nrf2的相互作用及其后续的泛素化修饰。这一作用抑制了Nrf2的降解，并减弱了STING的激活。在HSE小鼠模型中，CH显著降低了脑组织中的病毒载量，提高了小鼠存活率，防止体重下降，并缓解了神经症状。此外，CH在体内可促进Nrf2的积累，并抑制STING-NF-κB信号通路。综上所述，这些结果表明CH有望成为治疗HSE的潜在抗病毒策略。
- 单纯疱疹病毒性脑炎
- , 神经炎症
- , 盐酸千金藤碱
- , 核因子E2相关因子2
- , 干扰素基因刺激因子/核因子κB通路

Cepharanthine hydrochloride alleviates herpesvirus encephalitis by inhibiting Nrf2 degradation

Qiongzhen Zeng ^a,b ,
Weixiangmin Zou ^a,c ,
Jiaqi Wu ^a,c ,
Menghe Li ^a,c ,
Zexu Wang ^a,c ,
Caiwenjie La ^a,c ,
Cuifang Ye ^a ,
Zhe Ren ^a,c,, ,
Yifei Wang ^a,c,, ,
Kai Zheng ^d,,

a. Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China;
b. Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China;
c. Institute of Biomedicine, Guangdong Province Key Laboratory of Bioengineering Medicine, Key Laboratory of Innovative Technology Research on Natural Products and Cosmetics Raw Materials, Jinan University, Guangzhou 510632, China;
d. School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China

Corresponding author: Zhe Ren, rz62@163.com Yifei Wang, twang-yf@163.com Kai Zheng, zhengk@szu.edu.cn
Received Date: 09 October 2025
Accepted Date: 30 March 2026

Abstract

Herpes simplex virus type 1 (HSV-1) infection can induce herpes simplex encephalitis (HSE), a life-threatening neurological disorder characterized by active viral replication within the central nervous system accompanied by excessive neuroinflammatory responses. Cepharanthine hydrochloride (CH) is a natural bisbenzylisoquinoline alkaloid with diverse pharmacological activities. CH was evaluated for its antiviral and anti-inflammatory activities against HSV-1 infection. In microglia, CH markedly inhibited viral replication and suppressed STING-NF-κB signaling, thereby reducing HSV-1-associated neuroinflammation. During HSV-1 infection, CH binds to Nrf2, disrupting Keap1-Nrf2 interaction and subsequent ubiquitination. This hindered Nrf2 degradation and attenuated STING activation. In an HSE mouse model, CH significantly reduced viral loads in brain tissue, improved survival rates, prevented weight loss, and alleviated neurological symptoms. Furthermore, CH promoted the accumulation of Nrf2 and inhibited the STING-NF-κB signaling pathway in vivo. Collectively, these results indicate that CH represents a potential antiviral strategy for HSE.
- Herpes simplex encephalitis (HSE)
- , Neuroinflammation
- , Cepharanthine hydrochloride (CH)
- , Nrf2
- , STING-NF-κB pathway

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10.1016j.virs.2026.03.016-ESM.docx