AST2017-01 mainly consists of Rumex crispus and -Cordyceps militaris and has been widely consumed as an herbal medicine or functional food in Korea. Here we investigated the influences of AST2017-01 and its active component, chrysophanol on human mast cell (HMC-1 cell) and human keratinocyte (HaCaT cell)-mediated inflammatory reactions. Pretreatment with AST2017-01 or chrysophanol suppressed intracellular calcium levels and histamine release in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-treated HMC-1 cells. Levels of phosphorylated-mitogen-activated protein kinase increased by PMACI stimulation were reduced by AST2017-01 or chrysophanol pretreatment. Protein levels of IκB kinaseβ and receptor-interacting protein 2 in PMACI-treated HMC-1 cells were decreased by AST2017-01 or chrysophanol pretreatment. Pretreatment with AST2017-01 or chrysophanol significantly blocked PMACI-induced activation of caspase-1 and nuclear factor-κB. In addition, pretreatment with AST2017-01 or chrysophanol significantly decreased the PMACI-induced levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and thymic stromal lymphopoietin (TSLP) on HMC-1 cells. In activated HaCaT cells, pretreatment with AST2017-01 or chrysophanol significantly reduced production of TSLP and activation of caspase-1. In conclusion, these findings indicate that chrysophanol is an active component of AST2017-01 and AST2017-01 acts as a novel potent anti-inflammatory herbal medicine or functional food.