The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro.
10.1016/j.joim.2023.03.003
- Author:
Tong LIU
1
;
Qing-Qing SHAO
1
;
Wen-Jia WANG
1
;
Tian-Li LIU
1
;
Xi-Ming JIN
1
;
Li-Jun XU
1
;
Guang-Ying HUANG
1
;
Zhuo CHEN
2
Author Information
1. Institute of Integrated Traditional Chinese and Western Medicine, Department of Traditional Chinese Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
2. Institute of Integrated Traditional Chinese and Western Medicine, Department of Traditional Chinese Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China. Electronic address: chenz@tjh.tjmu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- Keywords:
Herpes simplex virus type 2;
Inflammasome;
Pyroptosis;
Traditional Chinese medicine
- MeSH:
Caspase 1/metabolism*;
Inflammasomes/pharmacology*;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*;
Pyroptosis;
Simplexvirus/metabolism*;
Drugs, Chinese Herbal/pharmacology*;
Herpes Simplex/drug therapy*;
Humans
- From:
Journal of Integrative Medicine
2023;21(3):277-288
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.
METHODS:HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.
RESULTS:HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).
CONCLUSION:JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.
