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山香圆果实乙醇提取物通过抑制Src发挥抗炎作用。

Anti-inflammatory effect of torilidis fructus ethanol extract through inhibition of Src.

作者信息

Park Gyubyung, Kim Eunji, Son Young-Jin, Yoon Deok Hyo, Sung Gi-Ho, Aravinthan Adithan, Park Yung Chul, Kim Jong-Hoon, Cho Jae Youl

机构信息

a Gyeonggi Science High School for the Gifted , Suwon , Republic of Korea.

b Department of Genetic Engineering , Sungkyunkwan University , Suwon , Republic of Korea.

出版信息

Pharm Biol. 2017 Dec;55(1):2074-2082. doi: 10.1080/13880209.2017.1362011.

DOI:10.1080/13880209.2017.1362011
PMID:28832235
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6130681/
Abstract

CONTEXT

Torilidis fructus, fruits of Torilis japonica Decadolle (Umbelliferae), is a medicinal herb traditionally used as a pesticide, an astrictive, or a medicine for various inflammatory diseases.

OBJECTIVES

Due to the lack of pharmacological studies on this herbal medicine, we explored the inhibitory activity of torilidis fructus on the macrophage-mediated inflammatory response using its ethanol extract (Tf-EE).

MATERIAL AND METHODS

The Griess assay and prostaglandin (PGE) ELISA assay were conducted with Tf-EE (0-75 µg/mL) and LPS (1 µg/mL) treated RAW264.7 cells in cultured media. Tf-EE pretreated RAW264.7 cells were incubated with LPS for 6 h and semi-quantitative PCR was performed. Reporter gene assays, overexpression of target enzymes and immunoblotting were performed on macrophages to determine the molecular targets of Tf-EE.

RESULTS

Tf-EE markedly suppressed the inflammatory response of macrophages, such as lipopolysaccharide (LPS)-induced nitric oxide (NO) and PGE production with IC values of 35.66 and 62.47 µg/mL, respectively. It was also found that Tf-EE reduced the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 by 80%. Nuclear translocation and activation of nuclear factor (NF)-κB (p65 and p50) were declined by 60% and 30% respectively, and their regulatory events including the phosphorylation of AKT, IκBα, Src, and the formation of complexes between Src and p-p85 were also recognized to be diminished.

CONCLUSIONS

The signalling events managed by Src and p85 complex seemed to be critically involved in Tf-EE-mediated anti-inflammatory response. This might suggest that Tf-EE exhibited anti-inflammatory effects through Src-targeted inhibition of NF-κB.

摘要

背景

蛇床子,即日本蛇床(伞形科)的果实,是一种传统上用作杀虫剂、收敛剂或治疗各种炎症性疾病的草药。

目的

由于对这种草药缺乏药理学研究,我们使用其乙醇提取物(Tf-EE)探索了蛇床子对巨噬细胞介导的炎症反应的抑制活性。

材料与方法

在培养基中用Tf-EE(0-75μg/mL)和脂多糖(LPS,1μg/mL)处理RAW264.7细胞,进行Griess法和前列腺素(PGE)ELISA检测。将经Tf-EE预处理的RAW264.7细胞与LPS孵育6小时,进行半定量PCR。对巨噬细胞进行报告基因检测、靶酶过表达和免疫印迹,以确定Tf-EE的分子靶点。

结果

Tf-EE显著抑制巨噬细胞的炎症反应,如脂多糖(LPS)诱导的一氧化氮(NO)和PGE生成,IC值分别为35.66和62.47μg/mL。还发现Tf-EE使诱导型NO合酶(iNOS)和环氧化酶(COX)-2的表达降低了80%。核因子(NF)-κB(p65和p50)的核转位和激活分别下降了60%和30%,其调控事件包括AKT、IκBα、Src的磷酸化以及Src与p-p85之间复合物的形成也被认为减少。

结论

由Src和p85复合物介导的信号事件似乎在Tf-EE介导的抗炎反应中起关键作用。这可能表明Tf-EE通过Src靶向抑制NF-κB发挥抗炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d6/6130681/387ec1bd5e60/IPHB_A_1362011_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d6/6130681/bea72296393b/IPHB_A_1362011_F0001a_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d6/6130681/4d96e48197f8/IPHB_A_1362011_F0001b_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d6/6130681/48a88374b10f/IPHB_A_1362011_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d6/6130681/b6dc4eb86cf7/IPHB_A_1362011_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d6/6130681/387ec1bd5e60/IPHB_A_1362011_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d6/6130681/bea72296393b/IPHB_A_1362011_F0001a_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d6/6130681/4d96e48197f8/IPHB_A_1362011_F0001b_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d6/6130681/48a88374b10f/IPHB_A_1362011_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d6/6130681/b6dc4eb86cf7/IPHB_A_1362011_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0d6/6130681/387ec1bd5e60/IPHB_A_1362011_F0004_C.jpg

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