Comparative Phytochemical and Antiviral Characteristics of Dipsacus asperoides and Phlomis umbrosa Against Influenza A Virus: LC-QTOF-MS Profiling and Exploratory Network Pharmacology
TL;DR
Despite clearly different phytochemical profiles, the two Sokdan species showed a shared pattern of modest in vitro antiviral response and should be interpreted as hypothesis-generating rather than mechanistic confirmation and suggest candidate host-response pathways that can guide targeted follow-up experiments.
Abstract
Background: Influenza A virus (IAV) remains an important respiratory pathogen, and medicinal plants continue to provide chemically diverse sources for antiviral research. Dipsacus asperoides and Phlomis umbrosa have both been used under the traditional name ‘Sokdan’ despite their distinct botanical origins and phytochemical compositions. This study comparatively characterized their chemical profiles and in vitro responses to IAV and used network pharmacology as an exploratory approach to identify candidate pathways for subsequent mechanistic studies. Methods: Ethanolic extracts were evaluated for cytotoxicity in MDCK cells, cytopathic effect (CPE) reduction against IAV A/PR/8/34 (H1N1), and neuraminidase (NA) inhibition. LC-QTOF-MS was used for qualitative chemical profiling, and species-specific compound sets were subjected to target prediction, protein–protein interaction analysis, and pathway enrichment. Results: D. asperoides was non-cytotoxic up to 100 µg/mL and P. umbrosa up to 300 µg/mL under the tested conditions. Both extracts produced modest CPE reduction, reaching maximum inhibition of 21.8 ± 1.4% at 100 µg/mL for D. asperoides and 17.1 ± 6.1% at 200 µg/mL for P. umbrosa, whereas zanamivir (5 µM) produced 76.2 ± 0.8% inhibition. NA inhibition was limited for both extracts. LC-QTOF-MS identified twelve constituents with distinct species-associated detection patterns, including phenylpropanoids, iridoid glycosides, and triterpenoid saponins. Exploratory network analysis identified partially overlapping predicted hubs, including MAPK1/3, RELA, IL-6, TNF, and CASP3, together with additional species-specific nodes. Conclusions: Despite clearly different phytochemical profiles, the two Sokdan species showed a shared pattern of modest in vitro antiviral response. The network pharmacology results should be interpreted as hypothesis-generating rather than mechanistic confirmation and suggest candidate host-response pathways that can guide targeted follow-up experiments. These findings support phytochemical differentiation of the two species while providing a comparative framework for future investigation of their antiviral properties.