Inhibition of neuraminidase activity by polyphenol compounds isolated from the roots of Glycyrrhiza uralensis

We isolated 18 polyphenols with neuraminidase inhibitory activity from methanol extracts of the roots of Glycyrrhiza uralensis. These polyphenols consisted of four chalcones (1–4), nine flavonoids (5–13), four coumarins (14–17), and one phenylbenzofuran (18). When we tested the effects of these individual compounds and analogs thereof on neuraminidase activation, we found that isoliquiritigenin (1, IC₅₀ = 9.0 μM) and glycyrol (14, IC₅₀ = 3.1 μM) had strong inhibitory activity. Structure–activity analysis showed that the furan rings of the polyphenols were essential for neuraminidase inhibitory activity, and that this activity was enhanced by the apioside group on the chalcone and flavanone backbone. In addition, the presence of a five-membered ring between C-4 and C-2′ in coumestan was critical for neuraminidase inhibition. All neuraminidase inhibitors screened were found to be reversible noncompetitive inhibitors.