Exploration of the mechanisms and active compounds of Scutellaria barbata D. Don against influenza A (H1N1) virus

Abstract

Scutellaria barbata D. Don ( S. barbata ), a traditional Chinese medicinal herb widely used for its heat-clearing and detoxifying properties, has shown broad-spectrum antiviral potential. However, its anti-H1N1 activity and underlying mechanisms remain to be fully elucidated. In this study, the anti-H1N1 activity and underlying mechanisms of S. barbata extract were investigated using H1N1-infected MDCK cells and BALB/c mice. Transcriptomic analysis followed by mRNA and protein-level validation was performed to characterize its molecular effects, while UPLC-Q-Orbitrap-MS was used to identify blood-absorbed constituents. Potential active compounds were subsequently screened by integrating the absorbed constituents with network pharmacology and further validated in vitro and in vivo . S. barbata extract markedly inhibited H1N1 replication in MDCK cells (IC 50 = 42.87 μg/mL; CC 50 > 500 μg/mL) and reduced viral burden and pulmonary inflammation in infected mice. Mechanistically, S. barbata treatment suppressed the Toll-like receptor, NF-κB, and chemokine signaling pathways, suggesting coordinated regulation of antiviral and inflammatory responses. Among the blood-absorbed constituents, baicalein and chrysoeriol were identified as key candidate active compounds and exhibited potent anti-H1N1 activity in vitro and in vivo (IC 50 = 13.80 and 11.10 μM, respectively). Collectively, these findings demonstrate that S. barbata exerts anti-H1N1 effects through a combination of direct inhibition of viral replication and modulation of excessive inflammatory responses, with baicalein and chrysoeriol representing important contributors to its antiviral activity.