高良姜对RAW 264.7细胞中TLR4/MyD88/p38MAPK和JAK/STAT通路的下调揭示了其在炎症中的有益作用。
Downregulation of TLR4/MyD88/p38MAPK and JAK/STAT pathway in RAW 264.7 cells by Alpinia galanga reveals its beneficial effects in inflammation.
作者信息
George Genu, Shyni G L, Abraham Billu, Nisha P, Raghu K G
机构信息
Biochemistry and Molecular Mechanism Laboratory, Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, Kerala, 695019, India.
Biochemistry and Molecular Mechanism Laboratory, Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, Kerala, 695019, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
出版信息
J Ethnopharmacol. 2021 Jul 15;275:114132. doi: 10.1016/j.jep.2021.114132. Epub 2021 Apr 20.
ETHNOPHARMACOLOGICAL RELEVANCE
Alpinia galanga, commonly known as greater galangal or raasna, is widely used in Ayurveda against various inflammatory disorders. It is also known as Kulinjan, Aratha, Rasna or Sugandhamula. Some of the Ayurvedic preparations using the rhizome of Alpinia galanga are Rasnadi kashayam, Rasna panchakam, Rasnapthakam, and Rasnarendadi. The aromatic rhizome is the source of the drug greater galangal and it is also used as a spice in South and South East Asia. However, the molecular mechanism of action of A galanga against inflammation remains poorly understood.
AIM OF THE STUDY
To elucidate the anti-inflammatory effect of hydroalcoholic extract of Alpinia galanga rhizome.
STUDY DESIGN/METHOD: The mechanism of the anti-inflammatory effect of hydroalcoholic extract of Alpinia galanga (AGE) was investigated by enzyme-linked immunosorbent assay (ELISA), Western blot, and immunofluorescence in LPS stimulated murine macrophage cell line (RAW 264.7). HPLC analysis was done to elucidate the rich polyphenolic nature of AGE.
RESULTS
The study showed that pre-treatment with AGE downregulated the release of pro-inflammatory mediators (IL-6, TNF-α, NO, and ROS) and stimulated the release of anti-inflammatory mediator IL-10 in LPS stimulated RAW 264.7 cells. The vital enzymes of inflammation (iNOS, COX-2, and MMP-9) were also downregulated by pre-treatment with AGE. AGE targeted the upstream elements of the inflammatory cascade by blocking LPS induced activation of TLR4 and JAK/STAT pathway. The phosphorylation of downstream kinases was significantly affected. The inhibition of nuclear translocation of NFκB further confirmed the specific inhibition of the TLR4 pathway. Particularly AGE inhibited the phosphorylation of JNK, p38, IκBα, and STAT. HPLC analysis of the AGE showed the polyphenol-rich nature of the extract.
CONCLUSIONS
The results from this study provide firm evidence that AGE exerts its anti-inflammatory effect via modulation of TLR4 and JAK/STAT pathway.
民族药理学相关性
高良姜，通常被称为大高良姜或拉什纳，在阿育吠陀医学中被广泛用于治疗各种炎症性疾病。它也被称为库林姜、阿拉塔、拉什纳或香根。一些使用高良姜根茎的阿育吠陀制剂有拉什纳迪卡夏姆、拉什纳五味剂、拉什纳普塔卡姆和拉什纳伦达迪。这种芳香的根茎是大高良姜药物的来源，在南亚和东南亚也被用作香料。然而，高良姜抗炎的分子作用机制仍知之甚少。
研究目的
阐明高良姜根茎水醇提取物的抗炎作用。
研究设计/方法：通过酶联免疫吸附测定（ELISA）、蛋白质印迹法和免疫荧光法，在脂多糖刺激的小鼠巨噬细胞系（RAW 264.7）中研究高良姜水醇提取物（AGE）抗炎作用的机制。进行高效液相色谱分析以阐明AGE富含多酚的性质。
结果
研究表明，在脂多糖刺激的RAW 264.7细胞中，预先用AGE处理可下调促炎介质（IL-6、TNF-α、NO和ROS）的释放，并刺激抗炎介质IL-10的释放。预先用AGE处理也可下调炎症关键酶（诱导型一氧化氮合酶、环氧化酶-2和基质金属蛋白酶-9）。AGE通过阻断脂多糖诱导的Toll样受体4（TLR4）和JAK/信号转导和转录激活因子（STAT）途径的激活，靶向炎症级联反应的上游元件。下游激酶的磷酸化受到显著影响。对核因子κB（NFκB）核转位的抑制进一步证实了对TLR4途径的特异性抑制。特别是AGE抑制了应激活化蛋白激酶（JNK）、p38、核因子κB抑制蛋白α（IκBα）和STAT的磷酸化。AGE的高效液相色谱分析表明提取物富含多酚。
结论
本研究结果提供了确凿证据，表明AGE通过调节TLR4和JAK/STAT途径发挥其抗炎作用。
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