Anti-inflammatory and antioxidant effects of 2, 7-dihydroxy-4, 6-dimethoxy phenanthrene isolated from Dioscorea batatas Decne

Our previous study showed that the ethanol extract of Dioscorea batatas Decne (Chinese yam) peel upregulated certain antioxidant enzymes and had the anti-inflammatory activity. In this study, 2, 7-dihydroxy-4, 6-dimethoxy phenanthrene (DDP) was isolated from yam peel extract as a potent antioxidative enzyme inducer through bioassay-guided fractionation using HepG2-ARE cells, and subjected to examination for its anti-inflammatory activity as well as antioxidant activity. DDP decreased the levels of inflammatory mediators in LPS-stimulated Raw 264.7 macrophage and reduced the level of reactive oxygen species in tert-butyl hydroperoxide-challenged Raw 264.7 cells. Moreover, DDP enhanced the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its downstream heme oxygenase-1 proteins while it decreased the expression of iNOS, COX-2, proinflammatory cytokines via nuclear factor-B pathway. However, the combinatorial treatment with DDP and the inhibitor of Nrf2 or HO-1 activity did not affect the levels of inflammatory biomarkers, suggesting that anti-inflammatory action by DDP is achieved by the mechanism independent of Nrf2 signaling pathway. In conclusion, DDP was found to be a strong antioxidant and anti-inflammatory agent and warrants further in vivo efficacy study for future use as a functional food ingredient.