Enhancement of Anti-inflammatory and Anti-allergic Activities with Combination of Luteolin and Quercetin in in vitro Co-culture System

Polyphenols are well known to possess diverse physiological functions. We have reported that luteolin suppressed tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 secretions in an in vitro co-culture system composed of RAW264.7 cells stimulated with lipopolysaccharide and Caco-2 cells, respectively. It was also reported that luteolin possessed anti-allergic activity with in vitro co-culture of Caco-2/RBL-2H3 cells. In this work, we investigated the activity of luteolin in combination with other polyphenols using both in vitro co-culture systems. Caco-2 cells were treated with the maximum concentration of luteolin (75 mu M) that did not produce anti-inflammatory activity, in combination with other polyphenols such as quercetin, kaempferol, curcumin, galangin and chrysin (each 75 mu M). All combinations of the tested polyphenols except chrysin significantly increased luteolin hyperpermeability to the basolateral side, curcumin in particular. The co-culture system analysis demonstrated that curcumin or quercetin in combination with luteolin significantly suppressed TNF-alpha production and IL -8 mRNA expression. Moreover, the combination of luteolin and quercetin suppressed beta-hexosaminidase activity as an index of anti-allergic activity. Combination of quercetin and luteolin was demonstrated to increase luteolin permeability to the basolateral compartment of the in vitro co-culture systems, resulting in the observed anti-inflammatory and anti-allergic activities.