Antiviral activity of processed <i>Rheum palmatum</i> L. extracts against the Influenza A H1N1 virus

Influenza A H1N1 (A/H1N1) poses a significant healthcare concern due to the potential to cause severe outcomes. Rheum palmatum L. (RP), an anthraquinone-rich rhubarb, possesses antiviral properties. However, the underlying mechanisms of these compounds in treating A/H1N1 remain unclear. This study investigated the effect of different processing methods on the antiviral activity of RP in vitro and evaluated the possible interactions of RP marker compounds with A/H1N1 in silico. Processed RP extracts were applied to A/H1N1-infected MDCK cells. Network pharmacology and molecular docking analyses were performed to establish its effects on functional A/H1N1-related gene clusters and validate interactions of RP compounds with A/H1N1. The raw and vinegar-processed RP ethanol extracts exhibited the highest antiviral activity. Network pharmacology revealed that RP metabolites affect four gene targets: MIF , NF- κ B , NFE2L2 , and TLR4 , which are mainly involved in NF-κB and NRF2 signaling pathways. Molecular docking results showed that aloe-emodin, emodin, and rhein exhibited good docking scores comparable to oseltamivir phosphate. These findings suggest that the major compounds in RP may possess antiviral activity against A/H1N1. This study provides preliminary evidence that could inform future studies assessing clinical efficacy and potential development as supportive anti-influenza agents.