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新型草药制剂庆熙柴胡汤-01通过RAW 264.7巨噬细胞中的JAK/STAT信号通路抑制脂多糖诱导的炎症反应。

Kyungheechunggan-Tang-01, a New Herbal Medication, Suppresses LPS-Induced Inflammatory Responses through JAK/STAT Signaling Pathway in RAW 264.7 Macrophages.

作者信息

Han Hee-Soo, Jang Eungyeong, Shin Ji-Sun, Inn Kyung-Soo, Lee Jang-Hoon, Park Geonha, Jang Young Pyo, Lee Kyung-Tae

机构信息

Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.

Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.

出版信息

Evid Based Complement Alternat Med. 2017;2017:7383104. doi: 10.1155/2017/7383104. Epub 2017 Nov 29.

Abstract

Medicinal plants have been used as alternative therapeutic tools to alleviate inflammatory diseases. The objective of this study was to evaluate anti-inflammatory properties of Kyungheechunggan-tang- (KCT-) 01, KCT-02, and Injinchunggan-tang (IJCGT) as newly developed decoctions containing 3-11 herbs in LPS-induced macrophages. KCT-01 showed the most potent inhibitory effects on LPS-induced NO, PGE, TNF-, and IL-6 production among those three herbal formulas. In addition, KCT-01 significantly inhibited LPS-induced iNOS and COX-2 at protein levels and expression of iNOS, COX-2, TNF-, and IL-6 at mRNA levels. Molecular data revealed that KCT-01 attenuated the activation of JAK/STAT signaling cascade without affecting NF-B or AP-1 activation. In ear inflammation induced by croton oil, KCT-01 significantly reduced edema, MPO activity, expression levels of iNOS and COX-2, and STAT3 phosphorylation in ear tissues. Taken together, our findings suggest that KCT-01 can downregulate the expression of proinflammatory genes by inhibiting JAK/STAT signaling pathway under inflammatory conditions. This study provides useful data for further exploration and application of KCT-01 as a potential anti-inflammatory medicine.

摘要

药用植物已被用作缓解炎症性疾病的替代治疗工具。本研究的目的是评估京畿청감탕(KCT)-01、KCT-02和茵陈청감탕(IJCGT)作为新开发的含有3-11种草药的汤剂在脂多糖诱导的巨噬细胞中的抗炎特性。在这三种草药配方中,KCT-01对脂多糖诱导的一氧化氮(NO)、前列腺素E(PGE)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的产生表现出最有效的抑制作用。此外,KCT-01在蛋白质水平上显著抑制脂多糖诱导的诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2),并在mRNA水平上抑制iNOS、COX-2、TNF-α和IL-6的表达。分子数据显示,KCT-01减弱了JAK/STAT信号级联的激活,而不影响核因子-κB(NF-κB)或激活蛋白-1(AP-1)的激活。在巴豆油诱导的耳部炎症中,KCT-01显著减轻耳部组织的水肿、髓过氧化物酶(MPO)活性、iNOS和COX-2的表达水平以及信号转导和转录激活因子3(STAT3)的磷酸化。综上所述,我们的研究结果表明,KCT-01在炎症条件下可通过抑制JAK/STAT信号通路下调促炎基因的表达。本研究为进一步探索和应用KCT-01作为潜在的抗炎药物提供了有用的数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd21/5733936/89cbb5ba8b94/ECAM2017-7383104.001.jpg

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