Bioactive constituents ofVerbena officinalisalleviate inflammation and enhance killing efficiency of natural killer cells

Abstract

Verbena officinalis L. (V. officinalis) has been used as a medical plant in traditional and modern medicine, exhibiting anti-tumor and anti-inflammation activity. In this work, we investigated the impact of bioactive constituents of V. officinalis on immune regulation. Using network pharmacology approaches, we analyzed potential regulatory roles of five compounds (Acteoside, Apigenin, Kaempferol, Verbenalin and Hastatoside) from V. officinalis on immune cell functions and revealed NK cells as a major target. The effect of these compounds on NK killing efficiency was examined with real-time killing assay, and Verbenalin enhanced NK killing efficiency significantly. Further investigation showed that Verbenalin did not affect proliferation, expression of cytotoxic proteins, or lytic granule degranulation, but rather reduced contact time required for killing therefore enhancing total killing events per NK cell, suggestively via inhibition of inhibitory receptors as determined by docking assay. Our findings reveal the underlying mechanisms how V. officinalis regulates functions of immune cells, especially NK cells, suggesting Verbenalin from V. officinalis as a promising therapeutic reagent to fight cancer and infection.