1. Academic Validation
  2. 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

  • Pharm Biol. 2022 Dec;60(1):451-466. doi: 10.1080/13880209.2022.2038209.
Tong Liu 1 Qingqing Shao 1 Wenjia Wang 1 Yonggui Ma 2 Tianli Liu 1 Ximing Jin 1 Jianguo Fang 2 Guangying Huang 1 Zhuo Chen 1
Affiliations

Affiliations

  • 1 Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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.

Keywords

Traditional Chinese Medicine; molecular docking; pyroptosis.

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