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Context: Verbascum phlomoides L. (Scrophulariaceae) (mullein) used in the European folk medicine due to its anti-inflammatory and soothing action on the respiratory tract is thoroughly documented in handbooks and scientific literature. Nevertheless, information regarding the influence of the polyphenol content on pharmacological activity is scarce. Objective: This study explored the antioxidant and anti-inflammatory potential of V. phlomoides polyphenol-rich extract. Materials and methods: Dried mullein flowers (200 g) were subjected to water extraction (60 °C, 2 h, herb/solvent ratio = 1/10 m/v) and further to n-butanol partition. Total phenolics were spectrophotometrically determined and specific compounds were evaluated by HPLC. The antioxidant activity was assessed by the 2,2-di(4- tert-octylphenyl)-1-picrylhydrazyl (DPPH) assay. The anti-inflammatory potential of the extract (50-200 μg/mL) was evaluated in vitro by ELISA measurement of ICAM-1 expression in TNF-α-stimulated endothelial cells and in vivo by the rat paw edema assay. Results: The mullein extract contained 4.18% total polyphenols expressed as gallic acid. The main components identified by HPLC were: rosmarinic acid (14.93 mg/g), caffeic acid (39.96 mg/g), ferulic acid (29.61 mg/g) and quercetin (17.29 mg/g). Acteoside was not detected; aucubin was detected in traces (0.028 mg/g). Depending on concentration, the extract exerted scavenging activity on DPPH radical (EC50 7.09 mg/mL), significantly inhibited TNF-α-induced ICAM-1 expression by 55-58.8% on human umbilical vein endothelial cells at 100 and 200 μg/mL, but failed to reduce egg-white-induced rat paw edema. Discussion and conclusion: Mullein polyphenols play an important role in exerting the antioxidant effect but have a weak influence on anti-inflammatory activity that is correlated, probably, to a higher content of iridoids and phenylethanoids. [ABSTRACT FROM AUTHOR]