The Chinese Herbal Prescription JieZe-1 Inhibits Membrane Fusion and the Toll-like Receptor Signaling Pathway in a Genital Herpes Mouse Model

Chinese herbal prescription JieZe-1 is effective for genital herpes with no visible adverse effects clinically. It showed an excellent anti-HSV-2 effect in vitro. However, its mechanism of anti-HSV-2 effect in vivo remains unclear. This study was designed to evaluate the anti-HSV-2 effect of JieZe-1...

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Main Authors: Qianni Duan, Tong Liu, Cong Huang, Qingqing Shao, Yonggui Ma, Wenjia Wang, Tianli Liu, Jun Sun, Jianguo Fang, Guangying Huang, Zhuo Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.707695/full
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author Qianni Duan
Tong Liu
Cong Huang
Qingqing Shao
Yonggui Ma
Wenjia Wang
Tianli Liu
Jun Sun
Jianguo Fang
Guangying Huang
Zhuo Chen
author_facet Qianni Duan
Tong Liu
Cong Huang
Qingqing Shao
Yonggui Ma
Wenjia Wang
Tianli Liu
Jun Sun
Jianguo Fang
Guangying Huang
Zhuo Chen
author_sort Qianni Duan
collection DOAJ
description Chinese herbal prescription JieZe-1 is effective for genital herpes with no visible adverse effects clinically. It showed an excellent anti-HSV-2 effect in vitro. However, its mechanism of anti-HSV-2 effect in vivo remains unclear. This study was designed to evaluate the anti-HSV-2 effect of JieZe-1 and berberine in a genital herpes mouse model and explore the underlying mechanism. The fingerprint of JieZe-1 was determined by high-performance liquid chromatography. First, we optimized a mouse model of genital herpes. Next, the weight, symptom score, morphological changes, viral load, membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells of vaginal tissue in mice at different time points were measured. Finally, we treated the genital herpes mouse model with JieZe-1 gel (2.5, 1.5, and 0.5 g/ml) and tested the above experimental indexes at 12 h and on the 9th day after modeling. JieZe-1 improved the symptoms, weight, and histopathological damage of genital herpes mice, promoted the keratin repair of tissues, and protected organelles to maintain the typical morphology of cells. It downregulated the expression of membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells. The vaginal, vulvar, and spinal cord viral load and vaginal virus shedding were also significantly reduced. In summary, JieZe-1 shows significant anti-HSV-2 efficacy in vivo. The mechanism is related to the inhibition of membrane fusion, the Toll-like receptor signaling pathway, inflammatory cytokines, and cellular immunity. However, berberine, the main component of JieZe-1 monarch medicine, showed no efficacy at a concentration of 891.8 μM (0.3 mg/ml).
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spelling doaj.art-592900cdb0c14a4dae0d04d2985acfaf2022-12-21T18:29:44ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-09-011210.3389/fphar.2021.707695707695The Chinese Herbal Prescription JieZe-1 Inhibits Membrane Fusion and the Toll-like Receptor Signaling Pathway in a Genital Herpes Mouse ModelQianni Duan0Tong Liu1Cong Huang2Qingqing Shao3Yonggui Ma4Wenjia Wang5Tianli Liu6Jun Sun7Jianguo Fang8Guangying Huang9Zhuo Chen10Department of TCM, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of TCM, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of TCM, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of TCM, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of TCM, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of TCM, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of TCM, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of TCM, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaChinese herbal prescription JieZe-1 is effective for genital herpes with no visible adverse effects clinically. It showed an excellent anti-HSV-2 effect in vitro. However, its mechanism of anti-HSV-2 effect in vivo remains unclear. This study was designed to evaluate the anti-HSV-2 effect of JieZe-1 and berberine in a genital herpes mouse model and explore the underlying mechanism. The fingerprint of JieZe-1 was determined by high-performance liquid chromatography. First, we optimized a mouse model of genital herpes. Next, the weight, symptom score, morphological changes, viral load, membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells of vaginal tissue in mice at different time points were measured. Finally, we treated the genital herpes mouse model with JieZe-1 gel (2.5, 1.5, and 0.5 g/ml) and tested the above experimental indexes at 12 h and on the 9th day after modeling. JieZe-1 improved the symptoms, weight, and histopathological damage of genital herpes mice, promoted the keratin repair of tissues, and protected organelles to maintain the typical morphology of cells. It downregulated the expression of membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells. The vaginal, vulvar, and spinal cord viral load and vaginal virus shedding were also significantly reduced. In summary, JieZe-1 shows significant anti-HSV-2 efficacy in vivo. The mechanism is related to the inhibition of membrane fusion, the Toll-like receptor signaling pathway, inflammatory cytokines, and cellular immunity. However, berberine, the main component of JieZe-1 monarch medicine, showed no efficacy at a concentration of 891.8 μM (0.3 mg/ml).https://www.frontiersin.org/articles/10.3389/fphar.2021.707695/fullChinese herbal prescription JieZe-1genital herpesherpes simplex virus type 2membrane fusiontoll-like receptor signaling pathwayimmune cells
spellingShingle Qianni Duan
Tong Liu
Cong Huang
Qingqing Shao
Yonggui Ma
Wenjia Wang
Tianli Liu
Jun Sun
Jianguo Fang
Guangying Huang
Zhuo Chen
The Chinese Herbal Prescription JieZe-1 Inhibits Membrane Fusion and the Toll-like Receptor Signaling Pathway in a Genital Herpes Mouse Model
Frontiers in Pharmacology
Chinese herbal prescription JieZe-1
genital herpes
herpes simplex virus type 2
membrane fusion
toll-like receptor signaling pathway
immune cells
title The Chinese Herbal Prescription JieZe-1 Inhibits Membrane Fusion and the Toll-like Receptor Signaling Pathway in a Genital Herpes Mouse Model
title_full The Chinese Herbal Prescription JieZe-1 Inhibits Membrane Fusion and the Toll-like Receptor Signaling Pathway in a Genital Herpes Mouse Model
title_fullStr The Chinese Herbal Prescription JieZe-1 Inhibits Membrane Fusion and the Toll-like Receptor Signaling Pathway in a Genital Herpes Mouse Model
title_full_unstemmed The Chinese Herbal Prescription JieZe-1 Inhibits Membrane Fusion and the Toll-like Receptor Signaling Pathway in a Genital Herpes Mouse Model
title_short The Chinese Herbal Prescription JieZe-1 Inhibits Membrane Fusion and the Toll-like Receptor Signaling Pathway in a Genital Herpes Mouse Model
title_sort chinese herbal prescription jieze 1 inhibits membrane fusion and the toll like receptor signaling pathway in a genital herpes mouse model
topic Chinese herbal prescription JieZe-1
genital herpes
herpes simplex virus type 2
membrane fusion
toll-like receptor signaling pathway
immune cells
url https://www.frontiersin.org/articles/10.3389/fphar.2021.707695/full
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