Caffeic acid regulates LPS-induced NF-κB activation through NIK/IKK and c-Src/ERK signaling pathways in endothelial cells.

The redox sensitive, proinflammatory nuclear transcription factor NF-κB plays a key role in inflammation. In a redox state disrupted by oxidative stress, pro-inflammatory genes are upregulated by the activation of NF-κB via diverse kinases. Thus, the search and characterization of new substances that modulate NF-κB are topics of considerable research interest. Caffeic acid is a component of garlic, some fruits, and coffee, and is widely used as a phenolic agent in beverages. In the present study, caffeic acid was examined with respect to the modulation of inflammatory NF-κB activation via the redox-related c-Src/ERK and NIK/IKK pathways via the reduction of oxidative stress. YPEN-1 cells (an endothelial cell line) were used to explore the molecular mechanism underlying the anti-inflammatory effect of caffeic acid by examining its modulation of NF-κB signaling pathway by LPS. Our results show that LPS-induced oxidative stress-related NF-κB activation upregulated pro-inflammatory COX-2, NF-κB targeting gene which were all inhibited effectively by caffeic acid. Our study shows that caffeic acid inhibits the activation of NF-κB via the c-Src/ERK and NIK/IKK signal transduction pathways. Our results indicate that antioxidative effect of caffeic acid and its restoration of redox balance are responsible for its anti-inflammatory action. Thus, the study provides new information regarding the anti-inflammatory properties of caffeic acid and the roles in the regulation of LPS-induced oxidative stress induces alterations in signal transduction pathways.