Investigating the effects of Laggera pterodonta on H3N2-Induced inflammatory and immune responses through network pharmacology, molecular docking, and experimental validation in a mice model

Yaorong Chen; Zexing Chen; Wanqi Wang; Yutao Wang; Jinyi Zhu; Xinhua Wang; Wanyi Huang

doi:10.1016/j.heliyon.2024.e29487

Investigating the effects of Laggera pterodonta on H3N2-Induced inflammatory and immune responses through network pharmacology, molecular docking, and experimental validation in a mice model

Heliyon. 2024 Apr 10;10(8):e29487. doi: 10.1016/j.heliyon.2024.e29487. eCollection 2024 Apr 30.

Authors

Yaorong Chen^{1

2}, Zexing Chen^{1

2}, Wanqi Wang^{1

2}, Yutao Wang¹, Jinyi Zhu^{1

2}, Xinhua Wang^{1

2}, Wanyi Huang^{1

2}

Affiliations

¹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510180, China.
² Institute of Integration of Traditional and Western Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Abstract

For centuries, Laggera pterodonta (LP), a Chinese herbal medicine, has been widely employed for treating respiratory infectious diseases; however, the mechanism underlying LP's effectiveness against the influenza A/Aichi/2/1968 virus (H3N2) remains elusive. This study aims to shed light on the mechanism by which LP combats influenza in H3N2-infected mice. First, we conducted quasi-targeted metabolomics analysis using liquid chromatography-mass spectrometry to identify LP components. Subsequently, network pharmacology, molecular docking, and simulation were conducted to screen candidate targets associated with AKT and NF-κB. In addition, we conducted a series of experiments including qPCR, hematoxylin-eosin staining, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay to provide evidence that LP treatment in H3N2-infected mice can reduce pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1β, and MCP-1) while increasing T cells (CD3⁺, CD4⁺, and CD8⁺) and syndecan-1 and secretory IgA expression. This, in turn, aids in the prevention of excessive inflammation and the fortification of immunity, both of which are compromised by H3N2. Finally, we utilized a Western blot assay to confirm that LP indeed inhibits the AKT/NF-κB signaling cascade. Thus, the efficacy of LP serves as a cornerstone in establishing a theoretical foundation for influenza treatment.

Keywords: Immunity; Inflammation; Influenza A/Aichi/2/1968 virus (H3N2); Laggera pterodonta; Molecular docking; Network pharmacology.