2. Academic Validation
  3. Regulation of Inflammatory Cytokines and Activation of PI3K/Akt Pathway by Yiqi Jiedu Formula in HSV-1-Induced Keratitis: Experimental and Network Pharmacology Evidence

Regulation of Inflammatory Cytokines and Activation of PI3K/Akt Pathway by Yiqi Jiedu Formula in HSV-1-Induced Keratitis: Experimental and Network Pharmacology Evidence

  • Virus Res. 2025 Mar 20:199561. doi: 10.1016/j.virusres.2025.199561.
Shuyu Xiao 1,  Wanhong Miao 1,  Leilei Wang 2,  Lei Wang 3,  Sisi Tang 4,  Huihui Xu 5,  Ying Yu 6
Affiliations

Affiliations

  • 1 Department of Ophthalmology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shuguang 201203, China.
  • 2 Department of Ophthalmology, Shanghai Eye Disease Control Center, Shuguang 200041, China.
  • 3 Department of Ophthalmology, Shanghai Seventh People's Hospital, Shuguang 201203, China.
  • 4 Department of Ophthalmology, Shanghai Songjiang District Fangta Traditional Chinese Medicine Hospital, Shuguang 201699, China.
  • 5 Department of Ophthalmology, Shanghai Aier Songchen Eye Hospital, Shuguang 201699, China.
  • 6 Department of Ophthalmology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shuguang 201203, China.. Electronic address: 1806060229@stu.hrbust.edu.cn.
PMID: 40120648 DOI: 10.1016/j.virusres.2025.199561
Abstract

Objective: This study investigates the therapeutic effects of the Yiqi Jiedu (YQJD) formula on Herpes Simplex Keratitis (HSK) induced by herpes simplex virus type 1 (HSV-1) and elucidates its mechanisms of action through experimental and network pharmacology approaches.

Methods: Active ingredients of the YQJD formula were identified using UPLC-HRMS. Network pharmacology was employed to predict shared targets between YQJD and HSK, focusing on the PI3K/Akt signaling pathway. Molecular docking was performed to assess the interaction between key ingredients and targets. In vivo, an HSK mouse model was used to evaluate the YQJD formula's impact on corneal lesions and inflammatory factors. In vitro, human corneal epithelial cells (HCECs) were infected with HSV-1 to assess the formula's effect on IL-4 expression.

Results: UPLC-HRMS identified 34 compounds in YQJD, with Isovitexin and Formononetin exhibiting high oral bioavailability. Network analysis revealed 97 intersecting targets, implicating the PI3K/Akt pathway in YQJD's mechanism. Molecular docking showed strong affinities between IL-4, IL-6, and YQJD compounds. In vivo, YQJD significantly improved corneal lesions and modulated the expression of IL-4, IL-6, and Akt. In vitro, YQJD-containing serum regulated IL-4 expression in HCECs post-HSV-1 Infection.

Conclusion: The YQJD formula ameliorates HSV-1-induced keratitis by regulating inflammatory cytokines and activating the PI3K/Akt pathway, offering a potential therapeutic strategy for HSK.

Keywords

Akt Signaling Pathway; Herpes Simplex Keratitis; Interleukin-4; Molecular Docking; Network Pharmacology.

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