Platycodin D restricts NDV replication via modulation of MAPK, NLRP3 inflammasome and interferon signaling

Platycodon grandiflorus (PG) is a traditional herb widely used for respiratory infections. Newcastle disease virus (NDV) is a highly contagious and devastating pathogen that causes severe economic losses to the poultry industry. Platycodin D (PD), a bioactive component of PG, has not been investigated for its antiviral activity against NDV.

We investigated the antiviral activity of PD against NDV and elucidated its underlying host-targeted mechanisms.

The anti-NDV activity of PD was evaluated in vitro and in vivo. Transcriptomic and network pharmacology were employed to map PD-targeted pathways. Mechanistic dissection was achieved by examining MAPK signaling cascade, NLRP3 inflammasome assembly, inflammatory cytokine profiling, apoptosis regulation, and type I interferon response.

PD significantly inhibited NDV replication in vitro and in vivo, reducing viral loads and tissue injury in infected chickens. Transcriptomic profiling combined with network pharmacology analysis identified inflammation-, apoptosis-, and interferon-related pathways as major targets of PD, with MAPK signaling emerging as a central regulatory node. Mechanistic studies demonstrated that PD suppressed NDV-induced activation of the MAPK pathway and NLRP3 inflammasome assembly, leading to decreased production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and IL-18). In parallel, PD attenuated virus-induced apoptosis through upregulation of the anti-apoptotic protein Bcl-2. Moreover, PD enhanced antiviral immunity by promoting IFN-α/β expression and STAT1 phosphorylation.

PD restricts NDV infection by coordinately modulating host inflammatory, apoptotic, and innate antiviral signaling pathways, supporting its potential as a host-targeted antiviral candidate for the control of Newcastle disease.