Evodia rutaecarpa and Three Major Alkaloids Abrogate Influenza A Virus (H1N1)-Induced Chemokines Production and Cell Migration

Evodia rutaecarpa is commonly used as an anti-inflammatory herbal remedy in traditional Chinese medicine. In this study, the ethanol extract of E. rutaecarpa (ER) and three major quinazoline alkaloids dehydroevodiamine (DeHE), evodiamine (Evo) and rutaecarpine (Rut), isolated from ER were employed to study their inhibitory effects against influenza A virus (H1N1)-induced chemokines production in A549 lung epithelial cells as well as on chemokines-evoked cell recruitment in HL-60-differentiated macrophages. The results showed that ER was a potent inhibitor of RANTES secretion by H1N1-inoculated A549 cells (IC(50): 1.9 ± 0.4 μg ml(-1)). Three alkaloids, although to differing extents, all concentration dependent, inhibited H1N1-induced RANTES production with Evo consistently being the most potent among these active components. ER also moderately and significantly inhibited H1N1-stimulated MCP-1 production in A549 cells. This was mimicked by Evo and Rut, but not DeHE. In the macrophage recruitment assay, both RANTES and MCP-1 markedly evoked cell migration and this phenomenon was significantly suppressed by ER. Evo and Rut, but not DeHE, also had the ability to inhibit cell migration toward RANTES and MCP-1, respectively. In summary, three major alkaloids displayed different potentials for inhibiting chemokines secretion and subsequently cell migration, which could partially explain the activity of ER. As an effective agent to suppress H1N1-induced chemokines production and block chemokine-attracted leukocytes recruitment, E. rutaecarpa and its active components may be useful in influenza virus infection-related inflammatory disorders.