In this study, we investigated the anti-inflammatory effects of red ginseng marc oil (RMO) in the RAW 264.7 macrophage cell line. RMO was prepared by a supercritical CO2 extraction of waste product generated after hot water extraction of red ginseng. RMO significantly inhibited the production of oxidative stress molecules such as nitric oxide and reactive oxygen species in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Levels of inflammatory targets including prostaglandin E2, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 were also reduced after the treatment with RMO. In addition, RMO diminished the expressions of inducible nitric oxide synthase and cyclooxygenase 2 at both mRNA and protein levels. Blockade of nuclear translocation of the p65 subunit of nuclear factor κB (NFκB) was also observed after the treatment of RMO. Furthermore, RMO decreased the phosphorylations of p38 mitogen-activated protein kinase (MAPK) and its upstream kinases including MAPK kinases 3/6 (MKK3/6) and TAK 1 (TGF-β activated kinase 1). Gas chromatographic analysis on RMO revealed that RMO contained about 10% phytosterols including sitosterol, stigmasterol and campesterol which may contribute to the anti-inflammatory properties of RMO. Taken together, these results suggest that the anti-inflammatory effect of RMO in LPS-induced RAW 264.7 macrophages could be associated with the inhibition of NFκB transcriptional activity, possibly via blocking the p38 MAPK pathway.

BackgroundThe induction of cellular defensive genes such as phase II detoxifying and antioxidant enzymes is a highly effective strategy for protection against carcinogenesis as well as slowing cancer development. Transcription factor Nrf2 (nuclear factor E2-related factor 2) is responsible for activation of phase II enzymes induced by natural chemopreventive compounds.MethodsRed ginseng oil (RGO) was extracted using a supercritical CO2 extraction system and chemical profile of RGO was investigated by GC/MS. Effects of RGO on regulation of the Nrf2/antioxidant response element (ARE) pathway were determined by ARE–luciferase assay, western blotting, and confocal microscopy.ResultsThe predominant components of RGO were 9,12-octadecadienoic acid (31.48%), bicyclo[10.1.0]tridec-1-ene (22.54%), and 22,23-dihydrostigmasterol (16.90%). RGO treatment significantly increased nuclear translocation of Nrf2 as well as ARE reporter gene activity, leading to upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase 1. Phosphorylation of the upstream kinases such as apoptosis signal-regulating kinase (ASK)1, mitogen-activated protein kinase (MAPK) kinase (MKK)4/7, c-Jun N-terminal kinase (JNK), and p38 MAPK were enhanced by treatment with RGO. In addition, RGO-mediated Nrf2 expression and nuclear translocation was attenuated by JNK inhibitor SP600125 and p38 MAPK inhibitor SB202190.ConclusionRGO could be used as a potential chemopreventive agent, possibly by induction of Nrf2/ARE-mediated phase II enzymes via ASK1–MKK4/7–JNK and p38 MAPK signaling pathways.

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