Mechanism of anti-influenza virus activity of Maillard reaction products derived from Isatidis roots
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The cyto-protective compositions and effects of antiviral Maillard reaction products (MRPs) derived from roots of Isatis indigotica F. were examined using biochemical and biophysical methods. The Maillard reaction was identified as the main source of compounds with antiviral activity, an observation which has led to the proposal of a new class of active compounds that protect cells from influenza virus infection. In the roots, arginine and glucose were revealed to be the predominant reactants for the Maillard reaction. Significant anti-influenza virus effects were demonstrated in the RIE MRPs derived from the roots (RIE refers to the ‘radix Isatidis extracts’), and in Arg-Glc MRPs which are synthesised with arginine and glucose. Arg-Glc MRPs were confirmed as suitable models for the study of the antiviral effects of the root extracts. Furthermore, RIE MRPs and Arg-Glc MRPs were found to bind to the plasma membranes of erythrocytes and MDCK cells, and altered their properties. A novel antiviral mechanism was proposed: that MRPs achieve their cyto-protective effects by binding to the cell membrane rather than by direct action on viral particles. To validate the proposed mechanism, the interaction between MRPs and membrane lipids was investigated by biophysical experiments with phospholipids bilayers. Arg-Glc MRPs affected the rigidity of lipid packing in monolayers and bilayers, while RIE MRPs enhanced the fluidity. Both types of MRPs inserted into the hydrophobic core of bilayers, to differing extents, and induced the stabilisation or destabilisation of bilayers in a concentrationdependent manner. At certain concentrations, MRPs prevented the lamellar structure of bilayers from being destabilised by a viral fusion peptide, improved the lipid order and thereby inhibited cell-virus membrane fusion. The mechanism of the anti-influenza virus activity of RIE was therefore correlated to the interaction between MRPs and phospholipid bilayers, an integral component of the plasma membrane.