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首页> 外文期刊>Medicines >Evidence for Anti-Inflammatory Activity of Isoliquiritigenin, 18β Glycyrrhetinic Acid, Ursolic Acid, and the Traditional Chinese Medicine Plants Glycyrrhiza glabra and Eriobotrya japonica , at the Molecular Level
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Evidence for Anti-Inflammatory Activity of Isoliquiritigenin, 18β Glycyrrhetinic Acid, Ursolic Acid, and the Traditional Chinese Medicine Plants Glycyrrhiza glabra and Eriobotrya japonica , at the Molecular Level

机译：在分子水平上异异黄体生成素，18β甘草次酸，熊果酸和中草药植物甘草和日本草的抗炎活性的证据

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Background: We investigated the effect of root extracts from the traditional Chinese medicine (TCM) plants Glycyrrhiza glabra L., Paeonia lactiflora Pall., and the leaf extract of Eriobotrya japonica (Thunb.) Lindl., and their six major secondary metabolites, glycyrrhizic acid, 18β glycyrrhetinic acid, liquiritigenin, isoliquiritigenin, paeoniflorin, and ursolic acid, on lipopolysaccharide (LPS)-induced NF-κB expression and NF-κB-regulated pro-inflammatory factors in murine macrophage RAW 264.7 cells. Methods: The cytotoxicity of the substances was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. RAW 264.7 cells were treated with LPS (1 μg/mL) or LPS plus single substances; the gene expression levels of NF-κB subunits (RelA, RelB, c-Rel, NF-κB1, and NF-κB2), and of ICAM-1, TNF-α, iNOS, and COX-2 were measured employing real-time PCR; nitric oxide (NO) production by the cells was quantified with the Griess assay; nuclear translocation of NF-κB was visualized by immunofluorescence microscopy with NF-κB (p65) staining. Results: All the substances showed moderate cytotoxicity against RAW 264.7 cells except paeoniflorin with an IC 50 above 1000 μM. Glycyrrhiza glabra extract and Eriobotrya japonica extract, as well as 18β glycyrrhetinic acid and isoliquiritigenin at low concentrations, inhibited NO production in a dose-dependent manner. LPS upregulated gene expressions of NF-κB subunits and of ICAM-1, TNF-α, iNOS, and COX-2 within 8 h, which could be decreased by 18β glycyrrhetinic acid, isoliquiritigenin and ursolic acid similarly to the anti-inflammatory drug dexamethasone. NF-κB translocation from cytoplasm to nucleus was observed after LPS stimulation for 2 h and was attenuated by extracts of Glycyrrhiza glabra and Eriobotrya japonica , as well as by 18β glycyrrhetinic acid, isoliquiritigenin, and ursolic acid. Conclusions: 18β glycyrrhetinic acid, isoliquiritigenin, and ursolic acid inhibited the gene expressions of ICAM-1, TNF-α, COX-2, and iNOS, partly through inhibiting NF-κB expression and attenuating NF-κB nuclear translocation. These substances showed anti-inflammatory activity. Further studies are needed to elucidate the exact mechanisms and to assess their usefulness in therapy.
机译：背景：我们研究了中药（Gymcyrrhiza glabra L.），Pa药（Paeonia lactiflora Pall。）和大叶草（Eriobotrya japonica（Thunb。Lindlin。））的叶提取物及其六种主要次生代谢产物甘草酸的根提取物的作用。酸，18β甘草次酸，脂蛋白原，异硫蛋白原，pa药苷和熊果酸对脂多糖（LPS）诱导的鼠巨噬细胞RAW 264.7细胞中NF-κB表达和NF-κB调节促炎因子的影响。方法：采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物（MTT）方法测定该物质的细胞毒性。用LPS（1μg/ mL）或LPS加单一物质处理RAW 264.7细胞;实时测量NF-κB亚基（RelA，RelB，c-Rel，NF-κB1和NF-κB2）以及ICAM-1，TNF-α，iNOS和COX-2的基因表达水平PCR;细胞的一氧化氮（NO）产生量用Griess测定法定量。通过NF-κB（p65）染色的免疫荧光显微镜观察NF-κB的核易位。结果：除pa药苷的IC 50高于1000μM外，所有物质均对RAW 264.7细胞显示中度细胞毒性。甘草提取物和大叶草提取物以及低浓度的18β甘草次酸和异黄体生成素以剂量依赖的方式抑制NO的产生。 LPS可以在8小时内上调NF-κB亚基以及ICAM-1，TNF-α，iNOS和COX-2的基因表达，与抗炎药地塞米松类似，可被18β甘草次酸，异黄体生成素和熊果酸所降低。 LPS刺激2 h后观察到NF-κB从细胞质向细胞核移位，并被甘草提取物和日本草rio提取物以及18β甘草次酸，异异黄体生成素和熊果酸所减弱。结论：18β甘草次酸，异黄体生成素和熊果酸抑制ICAM-1，TNF-α，COX-2和iNOS的基因表达，部分是通过抑制NF-κB表达和减弱NF-κB核易位。这些物质显示出抗炎活性。需要进一步研究以阐明确切机制并评估其在治疗中的有效性。

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