Anti-Inflammatory Effects of the Combined Treatment of Resveratrol- and Protopanaxadiol-Enriched Rice Seed Extract on Lipopolysaccharide-Stimulated RAW264.7 Cells

The overproduction of proinflammatory cytokines triggers a variety of diseases. Protopanaxadiol (PPD) and resveratrol are naturally found in plants such as ginseng and have potential anti-inflammatory properties, and resveratrol- and PPD-enriched rice seeds have been previously successfully generated. Herein, the synergistic anti-inflammatory activities of extracts of these enriched seeds were assessed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In comparison with treatment using extract prepared from PPD-producing transgenic rice (DJ-PPD) alone, cotreatment with DJ526 and DJ-PPD (TR_3) markedly enhanced the anti-inflammatory activities at a similar (compared to DJ526) or higher (compared to DJ-PPD) level. Cotreatment with DJ526 and DJ-PPD markedly inhibited the activation of nuclear factor kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) signaling pathways. Thus, DJ526 and DJ-PPD in combination suppressed the expression of phosphorylated (p)-NF-kappa B p65, p-p38 MAPK, and p-ERK 1/2. Cotreatment with DJ526 and DJ-PPD downregulated the expression of proinflammatory cytokines (IL-1 beta, IL-6, and TNF-alpha), LPS receptor (toll-like receptor-4, TLR-4), proinflammatory mediators (nitric oxide and PGE(2)), and arachidonic acid pathway critical enzyme (COX-2). These findings demonstrate the synergistic potential anti-inflammatory activities of resveratrol- and PPD-enriched rice seed extract.