ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Virus and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1627863
This article is part of the Research TopicViral Pathogenesis and Host Defense: Understanding the Missing Links to Combat DiseaseView all 4 articles
Flavonoid Compound from Forsythia suspensa leaves Inhibit Adenovirus Infection Related to Cell Cycle Based on UHPLC-Q-Exactive-Orbitrap/MS And Experimental Validation
Provisionally accepted
- 1School of Comprehensive Health Management,Xihua University, Chengdu, China
- 2Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China
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Forsythia suspensa leaves (FSL), a traditional herbal material in Chinese ethnomedicine for preparing health-promoting infusions, have been pharmacologically characterized for their robust anti-inflammatory, antioxidant, and broad-spectrum antiviral activities. Herein, we identified 39 active components from FSL primarily comprising organic acids, terpenoids, flavonoids, and lignans through UHPLC-Q-Exactive-Orbitrap/MS. Integrated analysis of GEO data revealed 990 adenovirus-associated differentially expressed genes, with network pharmacology and functional enrichment analyses further demonstrated that FSL flavonoids' preferential targeting of cell cycle regulators. In silico validation the stable binding of FSL-derived flavonoids to core cell cycle proteins through ensemble molecular docking and simulations. In vitro validation showed FSL dose-dependently inhibited HAdV replication, suppressing viral gene expression and E1A protein levels. Mechanistic investigations revealed that FSL exerts antiviral activity through coordinated regulation of cell cycle checkpoints. Flow cytometric analysis demonstrated dose-dependent G2/M phase arrest, accompanied by downregulation of CDC25A expression and upregulation of CCNB2, AURKA, CHEK1 and CCNA2 expression, thereby effectively blocking HAdV-induced cell cycle progression into S-phase (viral DNA replication phase). These findings establish a pharmacological foundation for developing FSL-derived phytotherapeutics against adenoviral infections.
Keywords: UHPLC-Q-Exactive-Orbitrap/MS, Forsythia suspensa leaves, adenovirus, Flavonoids, Cell Cycle
Received: 13 May 2025; Accepted: 17 Jul 2025.
Copyright: © 2025 Wang, Ren, Ma, Li, Zheng, Li and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lingling Wang, School of Comprehensive Health Management,Xihua University, Chengdu, China
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