Bioactive constituents of Verbena officinalis alleviate inflammation and enhance killing efficiency of natural killer cells

Natural killer (NK) cells play a key role in eliminating pathogen-infected cells. Verbena officinalis (V. officinalis) has been used as a medical plant in traditional and modern medicine, exhibiting anti-tumor and anti-inflammation activities, but its roles in immune responses still remains largely elusive. In this work, investigated the regulation of inflammation and NK functions by V. officinalis extract (VO-extract). In an influenza virus infection mouse model, oral administration of VO-extract alleviated lung injury, promoted maturation and activation of NK cells residing in the lung, and decreased the levels of inflammatory cytokines (IL-6, TNF- and IL-1{beta}) in the serum. We further analyzed the impact of five bioactive components of VO-extract on NK killing functions. Among them, Verbenalin enhanced NK killing efficiency significantly as determined by real-time killing assays based on plate-reader or high-throughput live-cell imaging in 3D using primary human NK cells. Further investigation showed that treatment of Verbenalin accelerated killing processes by reducing the contact time of NK cells with their target cells without affecting NK proliferation, expression of cytotoxic proteins, or lytic granule degranulation. Together, our findings reveal that low doses of V. officinalis can achieve a satisfactory anti-inflammation effect against viral infection in vivo, and V. officinalis regulates activation, maturation and killing functions of NK cells. NK killing efficiency is enhanced by Verbenalin from V. officinalis, suggesting a promising potential of verbenalin to fight viral infection.