Methylene chloride fraction of the leaves of Thuja orientalis inhibits in vitro inflammatory biomarkers by blocking NF-κB and p38 MAPK signaling and protects mice from lethal endotoxemia
- Methylene chloride fraction of the leaves of Thuja orientalis inhibits in vitro inflammatory biomarkers by blocking NF-κB and p38 MAPK signaling and protects mice from lethal endotoxemia
- 김진영; 김현정; 김성무; 박경란; 장흥진; 이은하; 정상훈; 안광석
- Thuja orientalis; NF-κB; MAPKs; Nitric oxide; COX; Endotoxemia; Cyclooxygenase-2
- Issue Date
- Journal of ethnopharmacology
- VOL 133, NO 2, 687-695
- Aim of the study: Thuja orientalis (TO) has been a recognized herbal medicine across Northeast Asian
countries for thousands of years and used for the treatment of various inflammatory diseases through as
yet undefined mechanisms. In this study, we set out to determine whether the anti-inflammatory effects
of this plant are mediated to suppress mitogen-activated protein kinases (MAPKs) and nuclear factor-κB
(NF-κB) activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.
Materials and methods: RAW 264.7 cells were pretreated with the methylene chloride fraction of TO
(MTO) and stimulated with LPS. Nitric oxide (NO) release was determined by the accumulation of nitrite
in the culture supernatants and tumor necrosis factor-α (TNF-α) and IL-6 secretion were determined by
immunoenzymatic assay. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression
were evaluated via RT-PCR and Western blotting. NF-κB activation was also evaluated by reporter
gene assay and electrophoretic mobility shift assay (EMSA). In addition, the protective effect of MTO was
evaluated by use of the LPS-induced endotoxin shock model in mice.
Results: We found that MTO significantly suppressed LPS-stimulated NO and IL-6 production without
affecting cell viability. MTO inhibited the expression of LPS-induced iNOS and COX-2 protein and their
mRNA expression. Also, TNF-α and IL-6 secretion were decreased by MTO in both PMA and ionomycinstimulated
splenocytes. As a result, MTO inhibited pro-inflammatory cytokines such as TNF-α and IL-6,
which is hypothesized as being due to the suppression of LPS-induced p38 MAPK and NF-κB activation.
Moreover,MTOimproved the survival rate during lethal endotoxemia by inhibiting the production of TNF-α in an animal model and our LC–MS analysis showed that a major component of MTO was pinusolide.
Conclusions: We demonstrate here the evidence that the methyl
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