Attenuation of Proinflammatory Responses by S-[6]-Gingerol via Inhibition of ROS/NF-Kappa B/COX2 Activation in HuH7 Cells

Introduction. Hepatic inflammation underlies the pathogenesis of chronic diseases such as insulin resistance and type 2 diabetes mellitus. S-[6]-Gingerol has been shown to have anti-inflammatory properties. Important inflammatory mediators of interleukins include nuclear factor kappa B (NF kappa B) and cyclooxygenase 2 (COX2). We now explore the mechanism of anti-inflammatory effects of S[ 6]-gingerol in liver cells. Methods. HuH7 cells were stimulated with IL1 beta to establish an in vitro hepatic inflammatory model. Results. S-[6]-Gingerol attenuated IL1 beta-induced inflammation and oxidative stress in HuH7 cells, as evidenced by decreasing mRNA levels of inflammatory factor IL6, IL8, and SAA1, suppression of ROS generation, and increasing mRNA levels of DHCR24. In addition, S-[6]-gingerol reduced IL1 beta-induced COX2 upregulation as well as NF kappa B activity. Similar to the protective effects of S[ 6]-gingerol, both NS-398 (a selective COX2 inhibitor) and PDTC (a selective NF kappa B inhibitor) suppressed mRNA levels of IL6, IL8, and SAA1. Importantly, PDTC attenuated IL1 beta-induced overexpression of COX2. Of particular note, the protective effect of S-[6]gingerol against the IL1 beta-induced inflammatory response was similar to that of BHT, an ROS scavenger. Conclusions. The findings of this study demonstrate that S-[6]-gingerol protects HuH7 cells against IL1 beta-induced inflammatory insults through inhibition of the ROS/NF kappa B/COX2 pathway.