Institute of Integrated Traditional Chinese and Western Medicine, Dept.of TCM, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
J Ethnopharmacol. 2020 Mar 1;249:112405. doi: 10.1016/j.jep.2019.112405. Epub 2019 Nov 16.
The Chinese Herbal Prescription JieZe-1(JZ-1), added and subtracted from Yihuang Decoction, a famous formula in the 12th year of Kangxi in Qing Dynasty, has a clear effect on Genital Herpes (GH) and no obvious adverse reactions occur clinically. JZ-1 also has preventive and therapeutic effects on Trichomonas vaginitis, Candida albicans vaginitis and GH in vitro and in vivo experiments.
The effect and mechanism of JZ-1 on anti-herpes simplex virus type 2(HSV-2) in vitro focusing on adhesion and penetration stages were investigated.
A model of HSV-2 infection of VK2/E6E7 was developed. In order to explore JZ-1's anti-HSV-2 effect in vitro, cell morphology, ultrastructural pathology, cell viability and expression of viral glycoprotein D (gD) were assessed at 6 h, 12 h, 18 h, and 24 h of JZ-1 treatment. Then we measured the exact time required for adhesion and penetration of HSV-2 into VK2/E6E7 among a series of times at room temperature and under temperature control techniques. We treated VK2/E6E7 with JZ-1, penciclovir, or berberine and explored the mechanism of JZ-1 in blocking HSV-2 adhesion and penetration of host cells by assessing the cell ultrastructural pathology, viability, viral proteins gB, gD, VP16, ICP5, and ICP4 and host cell proteins HVEM, Nectin-1, and Nectin-2.
HSV-2 can fully adhere and penetrate into VK/E6E7 within 5 mins at room temperature while it takes 60mins under temperature control techniques. JZ-1 and penciclovir showed significant anti-HSV-2 effects, with improved host cell morphologies and increased host cell viabilities observed after treatment for 24 h. The anti-HSV-2 effect of JZ-1 can be detected after treatment for 6 h while that of penciclovir was not obvious until treatment for 12 h. JZ-1 showed distinct effect on HSV-2 adhesion and penetration stages by significantly reducing the expression of viral proteins gB, gD, VP16, ICP5, and ICP4, improving cell morphology and increasing cell viability. However, these effects were not exerted via downregulated expression of membrane fusion-related proteins such as HVEM, Nectin-1, or Nectin-2. The specific anti-HSV-2 mechanism of JZ-1 need to be further explored.
The anti-HSV-2 effect of JZ-1 was superior to that of penciclovir and berberine in vitro, and was mainly mediated by enhancing host cell defense and blocking adhesion and penetration of HSV-2.
中药方剂解热 1 号（JZ-1）加减医黄汤，是清朝康熙 12 年的著名方剂，对生殖器疱疹（GH）有明确疗效，临床无明显不良反应。JZ-1 对滴虫性阴道炎、白色念珠菌性阴道炎和 GH 的体外和体内实验也有预防和治疗作用。
研究 JZ-1 在体外抗单纯疱疹病毒 2（HSV-2）的作用及其机制，重点研究粘附和渗透阶段。
建立 HSV-2 感染 VK2/E6E7 的模型。为了探讨 JZ-1 在体外抗 HSV-2 的作用，在 JZ-1 处理 6、12、18 和 24 小时时，评估细胞形态、超微结构病理学、细胞活力和病毒糖蛋白 D（gD）的表达。然后，我们在室温下和温度控制技术下，在一系列时间点测量 HSV-2 进入 VK2/E6E7 的粘附和渗透的确切时间。我们用 JZ-1、喷昔洛韦和小檗碱处理 VK2/E6E7，通过评估细胞超微结构病理学、活力、病毒蛋白 gB、gD、VP16、ICP5 和 ICP4 以及宿主细胞蛋白 HVEM、Nectin-1 和 Nectin-2，探讨 JZ-1 阻断 HSV-2 与宿主细胞粘附和渗透的机制。
HSV-2 在室温下 5 分钟内可完全粘附并渗透进入 VK/E6E7，而在温度控制技术下则需要 60 分钟。JZ-1 和喷昔洛韦均表现出显著的抗 HSV-2 作用，处理 24 小时后观察到宿主细胞形态改善和宿主细胞活力增加。JZ-1 的抗 HSV-2 作用可在处理 6 小时后检测到，而喷昔洛韦直到处理 12 小时后才显示出明显的效果。JZ-1 通过显著降低病毒蛋白 gB、gD、VP16、ICP5 和 ICP4 的表达、改善细胞形态和增加细胞活力，对 HSV-2 的粘附和渗透阶段表现出明显的作用。然而，这些作用不是通过下调 HVEM、Nectin-1 或 Nectin-2 等膜融合相关蛋白的表达来发挥的。JZ-1 的具体抗 HSV-2 机制需要进一步探索。
JZ-1 的抗 HSV-2 作用优于体外喷昔洛韦和小檗碱，主要通过增强宿主细胞防御和阻断 HSV-2 的粘附和渗透来介导。
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