151. Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription JieZe-1 in protecting against HSV-2 infection.
- Author
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Tong Liu, Qingqing Shao, Wenjia Wang, Yonggui Ma, Tianli Liu, Ximing Jin, Jianguo Fang, Guangying Huang, and Zhuo Chen
- Subjects
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SOMATOTROPIN receptors , *HERPES genitalis , *HERPES simplex virus , *PHARMACOLOGY , *PROTEIN expression , *MOLECULAR docking - 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 lL 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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