BACKGROUND Vaccinium oldhamii (V. oldhamii) has been reported to exert a variety of the pharmacological properties such as anti-oxidant activity, anti-cancer activity, and inhibitory activity of α-amylase and acetylcholinesterase. However, the anti-inflammatory activity of V. oldhamii has not been studied. In this study, we aimed to investigate anti-inflammatory activity of the stem extracts from V. oldhamii, and to elucidate the potential mechanisms in LPS-stimulated RAW264.7 cells. METHODS Cell viability was evaluated by MTT assay. The determination of NO and PGE2 production was performed using Griess reagent and Prostaglandin E2 ELISA Kit, respectively. The change of mRNA or protein level was evaluated by RT-PCR and Western blot. RESULTS Among VOS, VOL and VOF, the inhibitory effect of NO and PGE2 production induced by LPS was highest in VOS treatment. Thus, VOS was selected for the further study. VOS dose-dependently blocked LPS-induced NO and PGE2 production by inhibiting iNOS and COX-2 expression, respectively. VOS inhibited the expression of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. In addition, VOS suppressed TRAP activity and attenuated the expression of the osteoclast-specific genes such as NFATc1, c-FOS, TRAP, MMP-9, cathepsin K, CA2, OSCAR and ATPv06d2. VOS inhibited LPS-induced NF-κB signaling activation through blocking IκB-α degradation and p65 nuclear accumulation. VOS inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, VOS inhibited ATF2 phosphorylation and blocked ATF2 nuclear accumulation. CONCLUSIONS These results indicate that VOS may exert anti-inflammatory activity by inhibiting NF-κB and MAPK/ATF2 signaling. From these findings, VOS has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.

中文翻译：

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Vaccinium oldhamii的抗炎作用是通过抑制LPS刺激的RAW264.7细胞中的NF-κB和MAPK / ATF2信号激活来实现的。

背景技术已有报道，越桔越桔（V.oldhamii）具有多种药理特性，例如抗氧化活性，抗癌活性以及α-淀粉酶和乙酰胆碱酯酶的抑制活性。然而，尚未研究oldhamii的抗炎活性。在这项研究中，我们旨在调查V. oldhamii茎提取物的抗炎活性，并阐明LPS刺激的RAW264.7细胞的潜在机制。方法采用MTT法评价细胞活力。使用Griess试剂和前列腺素E2 ELISA试剂盒分别测定NO和PGE2的产生。通过RT-PCR和Western印迹评估mRNA或蛋白质水平的变化。在VOS，VOL和VOF中的结果 LPS诱导的NO和PGE2生成的抑制作用在VOS处理中最高。因此，选择了VOS进行进一步研究。VOS分别通过抑制iNOS和COX-2表达来剂量依赖性地阻断LPS诱导的NO和PGE2的产生。VOS抑制促炎细胞因子如IL-1β，IL-6和TNF-α的表达。此外，VOS抑制了TRAP活性并减弱了破骨细胞特异性基因（如NFATc1，c-FOS，TRAP，MMP-9，组织蛋白酶K，CA2，OSCAR和ATPv06d2）的表达。VOS通过阻止IκB-α降解和p65核蓄积来抑制LPS诱导的NF-κB信号激活。VOS通过减弱ERK1 / 2，p38和JNK的磷酸化来抑制MAPK信号激活。此外，VOS抑制了ATF2的磷酸化并阻止了ATF2的核积累。结论这些结果表明VOS可能通过抑制NF-κB和MAPK / ATF2信号传导发挥抗炎活性。根据这些发现，VOS有潜力成为炎症性疾病的化学预防剂或治疗剂开发的候选者。