Sorghum and cowpea contain structurally distinct flavonoids that may provide complementary bioactive properties. This study investigated the interactive effects of combining sorghum and cowpea flavonoids on inflammation and reactive oxygen species (ROS) generation in non-malignant colon myofibroblasts (CCD-18Co). The effect of sorghum-cowpea flavonoid combinations on ATP binding cassette (ABC) transporter proteins in Caco-2 cell model was also investigated. The White sorghum-white cowpea extract combinations at (0.1 ug/mL) synergistically (1.5-2 times) attenuated LPS-induced ROS generation as well as LPS-induced inflammation in non-cancer CCD-18Co cells by inhibiting the activation of NF-?B and related downstream targets such as IL-6, IL-8 and TNF-? at both mRNA and protein levels. Combination of pure apigenin (dominant flavonoid in white sorghum) and quercetin (prevalent flavonoid in white cowpea) demonstrated similar enhanced action (1.5-2 times) in protecting the CCD-18Co cells against ROS generation and inflammation at 0.1 uM, indicating the flavones and flavonols in sorghum-cowpea mixtures may be responsible for the observed synergistic effect. The magnitude of synergy was strongly dependent on the relative ratios of sorghum-cowpea and apigenin-quercetin mixtures, which suggests different mechanisms of action for the flavones and flavonols. The White sorghum-white cowpea as well as apigenin-quercetin combinations synergistically modified the activity of efflux transporters in Caco-2 cell monolayers by inhibiting the expression of apically located ABC transporters including BCRP, MRP2, MRP3 and MDR1 at both mRNA and protein levels. These results suggest that synergistic down-regulation of efflux transporter proteins could be a mechanism for enhanced action sorghum-cowpea combination against inflammation. Overall findings from these studies suggest that consuming sorghum and cowpea together may favorably influence health outcomes beyond what can be predicted from individual commodity. This is important because cereal and legumes are usually consumed together; strategic cereal and legume combinations might be formulated for optimized benefits in chronic disease prevention. Further in vivo studies with sorghum-cowpea diets are required to assess the physiological effects of sorghum-cowpea flavonoids mixtures on biomarkers of inflammation and chronic disease.
