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三种三萜类化合物从 L. 对脂多糖刺激的 RAW264.7 细胞的抗炎活性。

Anti-Inflammatory Activity of Three Triterpene from L. in Lipopolysaccharide-Stimulated RAW264.7 Cells.

机构信息

Center for Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, Yantai 264005, China.

Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China.

出版信息

Int J Mol Sci. 2021 Nov 5;22(21):12009. doi: 10.3390/ijms222112009.

Abstract

Oleanolic acid (OA), asiatic acid (AA), and maslinic acid (MA) are ubiquitous isomeric triterpene phytochemicals with many pharmacological effects. To improve their application value, we used lipopolysaccharide (LPS) to induce RAW264.7 cells and studied the differences in the anti-inflammatory effects of the triterpenes according to their structural differences. MTT, Griess, and immunofluorescence assays, ELISA, flow cytometry, and Western blotting, were performed. The release of LPS-induced pro-inflammatory mediators, such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), and interleukin (IL-6), was significantly inhibited by OA, AA, and MA at the same concentration, and AA and MA promoted the production of anti-inflammatory factor IL-10. OA, AA, and MA inhibited LPS-induced NF-κB nuclear translocation in RAW264.7 cells. OA and AA inhibited the phosphorylation of ERK1/2, P38, and JNK1/2 in LPS-stimulated RAW264.7 cells. Moreover, OA increased LPS-induced Nrf2 expression and decreased Keap1 expression in RAW264.7 cells. OA, AA, and MA inhibited LPS-stimulated intracellular reactive oxygen species (ROS) production and alleviated mitochondrial membrane potential depletion. Overall, our data suggested that OA, AA, and MA exhibited significant anti-inflammatory effects in vitro. In particular, OA and AA take effects through the MAPKs, NF-κB, and Nrf2 signaling pathways.

摘要

齐墩果酸(OA)、熊果酸(AA)和齐墩果酸(MA)是广泛存在的同分异构三萜植物化学物质,具有许多药理作用。为了提高它们的应用价值,我们使用脂多糖(LPS)诱导 RAW264.7 细胞,并根据它们的结构差异研究了三萜类化合物抗炎作用的差异。进行了 MTT、Griess 和免疫荧光测定、ELISA、流式细胞术和 Western blot。OA、AA 和 MA 在相同浓度下均能显著抑制 LPS 诱导的促炎介质(如一氧化氮(NO)、诱导型一氧化氮合酶(iNOS)和白细胞介素(IL-6))的释放,AA 和 MA 促进抗炎因子 IL-10 的产生。OA、AA 和 MA 抑制 LPS 诱导的 RAW264.7 细胞中 NF-κB 核易位。OA 和 AA 抑制 LPS 刺激的 RAW264.7 细胞中 ERK1/2、P38 和 JNK1/2 的磷酸化。此外,OA 增加 LPS 诱导的 RAW264.7 细胞中 Nrf2 的表达并降低 Keap1 的表达。OA、AA 和 MA 抑制 LPS 刺激的细胞内活性氧(ROS)产生并减轻线粒体膜电位耗竭。总体而言,我们的数据表明 OA、AA 和 MA 在体外均表现出显著的抗炎作用。特别是 OA 和 AA 通过 MAPKs、NF-κB 和 Nrf2 信号通路发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4960/8584548/44c5f6b04bf2/ijms-22-12009-g001.jpg

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