Antioxidant and Anti-inflammatory Activities of Zingiber montanum Oil in HepG2 Cells and Lipopolysaccharide-Stimulated RAW 264.7 Macrophages.

Abstract

Improvement of antioxidant and anti-inflammatory functions is believed to be an effective strategy for protection against various diseases such as cancer, aging, and neurodegenerative disease. This study focused on investigating antioxidant and anti-inflammatory abilities of Zingiber montanum oil (ZMO) extracted by the supercritical CO2 fluid system in HepG2 cells and lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Ten predominant constituents of ZMO were identified, in which triquinacene, 1,4-bis (methoxy), terpinen-4-ol, triquinacene, 1,4,7-tris (methoxy), α-terpinene, sabinene hydrate, and (E and Z)-1-(3,4-dimethoxyphenyl)butadiene account for 86.47%. ZMO exhibited anti-inflammatory capacity by inhibiting the formation of pro-inflammatory markers such as nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein-1 in LPS-treated macrophages. The LPS-induced stimulation of nuclear factor-kappa B, signal transducer and activator of transcription 3 (Stat3) and mitogen-activated protein kinase (MAPK) pathways as evident from increased phosphorylation of IKKα/β, IκBα, p65, Stat3, ERK, JNK, and p38 MAPK was also suppressed by ZMO pretreatment. Further, ZMO enhanced the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1), and concurrently, reduced intracellular reactive oxygen species accumulation in LPS-treated RAW 264.7 cells. In addition, ZMO treatment markedly upregulated the expression of Nrf2 as well as its target genes, HO-1 and NAD(P)H:quinone oxidoreductase 1 in HepG2 cells. These data propose that ZMO may be a potent candidate for prevention and/or treatment of inflammatory and oxidative conditions.