Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription JieZe-1 in protecting against HSV-2 infection.
Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription JieZe-1 in protecting against HSV-2 infection.
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结合网络药理学和实验验证破译中药解泽1预防HSV-2感染的机制
DOI：
10.1080/13880209.2022.2038209
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发表时间：
2022-12
影响因子：
3.8
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Liu T;Shao Q;Wang W;Ma Y;Liu T;Jin X;Fang J;Huang G;Chen Z
中文摘要中药复方洁泽1号（JZ-1）对单纯疱疹病毒2型（HSV-2）感染有效。然而，其机制仍不清楚。目的探讨JZ-1抗HSV-2感染的作用机制。材料与方法采用网络药理学方法，筛选和功能富集中枢成分和作用靶点。建立生殖器疱疹（GH）小鼠模型，观察其发病特点。然后，不同组中的GH小鼠（10只/组）分别用20 μL JZ-1凝胶（2.5、1.5和0.5 g/mL）、阿昔洛韦凝胶（0.03 g/mL）或普通卡波姆凝胶处理，每天两次。测量症状评分、外阴组织形态学和病毒载量。通过显微镜、免疫共沉淀、蛋白质印迹和ELISA分析caspase-1依赖性焦亡的关键蛋白。还进行了分子对接。结果通过网络药理学分析确定了388个与HSV-2感染相关的JZ-1靶点，筛选出36个中枢靶点和21个中枢成分。HSV-2的TCID 50为1 × 10−7/0.1 mL。JZ-1凝胶剂（2.5 g/mL）能有效降低GH小鼠症状评分（81.23%）、病毒载量（98.42%）和组织病理学改变，并能显著抑制caspase-1依赖的细胞凋亡蛋白表达（p< 0.05）。分子对接实验表明，11个组分与caspase-1或IL-1 β具有良好的结合能力。讨论和结论JZ-1对HSV-2感染小鼠有保护作用，并能抑制GH小鼠caspase-1依赖的细胞凋亡。这对JZ-1的二次开发和新药开发具有重要意义。
Abstract Context The Chinese herbal prescription JieZe-1 (JZ-1) is effective against HSV-2 (Herpes simplex virus type 2) infection. However, its mechanism remains unclear. Objective To explore the mechanism of JZ-1 in protecting against HSV-2 infection. Materials and methods Using the methods of network pharmacology, the hub components and targets were screened and functionally enriched. We established a genital herpes (GH) mouse model and observe the disease characteristics. Then, the GH mice in different groups (10 per/group) were treated with 20 μL JZ-1 gel (2.5, 1.5, and 0.5 g/mL), acyclovir gel (0.03 g/mL), or plain carbomer gel twice a day. The symptom score, vulvar histomorphology, and virus load were measured. The critical proteins of caspase-1–dependent pyroptosis were analysed by microscopy, co-immunoprecipitation, western blotting, and ELISA. Molecular docking was also performed. Results Network pharmacology analysis identified 388 JZ-1 targets related to HSV-2 infection, with 36 hub targets and 21 hub components screened. The TCID50 of HSV-2 was 1 × 10−7/0.1 mL. JZ-1 gel (2.5 g/mL) can effectively reduce the symptom score (81.23%), viral load (98.42%) and histopathological changes, and significantly inhibit the proteins expression of caspase-1–dependent pyroptosis in GH mice (p< 0.05). The molecular docking test showed a good binding potency between 11 components and caspase-1 or interleukin (IL)-1β. Discussion and conclusions The present study demonstrated that JZ-1 protected mice from HSV-2 infection and inhibit the caspase-1–dependent pyroptosis in GH mice. It is of significance for the second development of JZ-1 and the exploration of new drugs.
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