title: Attenuation of Proinflammatory Responses by S-[6]-Gingerol via Inhibition of ROS/NF-Kappa B/COX2 Activation in HuH7 Cells.
abstract: 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 κ B (NF κ 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 IL1β to establish an in vitro hepatic inflammatory model. Results. S-[6]-Gingerol attenuated IL1β-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 IL1β-induced COX2 upregulation as well as NF κ B activity. Similar to the protective effects of S-[6]-gingerol, both NS-398 (a selective COX2 inhibitor) and PDTC (a selective NF κ B inhibitor) suppressed mRNA levels of IL6, IL8, and SAA1. Importantly, PDTC attenuated IL1β-induced overexpression of COX2. Of particular note, the protective effect of S-[6]-gingerol against the IL1β-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 IL1β-induced inflammatory insults through inhibition of the ROS/NF κ B/COX2 pathway.
authors.affiliation: Heart Research Institute, Newtown, NSW 2042, Australia ; Faculty of Pharmacy, University of Sydney, Camperdown, NSW 2006, Australia ; Department of Endocrinology, Dezhou People's Hospital, Dezhou, Shandong 253014, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.forename: Kristine C Y
authors.initials: KC
authors.lastname: McGrath
authors.forename: Van H
authors.initials: VH
authors.lastname: Tran
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Li
authors.forename: Colin C
authors.initials: CC
authors.lastname: Duke
authors.forename: Basil D
authors.initials: BD
authors.lastname: Roufogalis
authors.forename: Alison K
authors.initials: AK
authors.lastname: Heather