川芎的抗炎物质筛选及其作用机制分析

马宁宁; 范姗姗; 李欣; 杨珍; 林梦雅; 王昊; 姜民; 张艳军; 庄朋伟; 宋丽丽

doi:10.13422/j.cnki.syfjx.20181701

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川芎的抗炎物质筛选及其作用机制分析

药理 | 更新时间：2024-01-04

- 川芎的抗炎物质筛选及其作用机制分析
- Screening of Anti-inflammatory Substances of Chuanxiong Rhizoma and Analysis of Its Mechanism
- 中国实验方剂学杂志 2018年24卷第18期页码：140-146
- 作者机构：
- 作者简介：
- 基金信息：
  
  天津市教委科研计划项目（2017KJ153）
- DOI：10.13422/j.cnki.syfjx.20181701
  中图分类号： R285.5
- 纸质出版日期：2018
- 稿件说明：
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马宁宁, 范姗姗, 李欣, 等. 川芎的抗炎物质筛选及其作用机制分析[J]. 中国实验方剂学杂志, 2018,24(18):140-146.

MA Ning-ning, FAN Shan-shan, LI Xin, et al. Screening of Anti-inflammatory Substances of Chuanxiong Rhizoma and Analysis of Its Mechanism[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(18): 140-146.
马宁宁, 范姗姗, 李欣, 等. 川芎的抗炎物质筛选及其作用机制分析[J]. 中国实验方剂学杂志, 2018,24(18):140-146. DOI： 10.13422/j.cnki.syfjx.20181701.

MA Ning-ning, FAN Shan-shan, LI Xin, et al. Screening of Anti-inflammatory Substances of Chuanxiong Rhizoma and Analysis of Its Mechanism[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(18): 140-146. DOI： 10.13422/j.cnki.syfjx.20181701.

摘要

目的：研究川芎不同提取物UPLC指纹图谱与其抗炎药效之间的谱效关系，确定川芎的活性成分群，初步阐述其网络调控机制。方法：采用UPLC-Q-TOF/MS对川芎8组提取物的成分进行分析，以人支气管上皮细胞为研究对象，考察川芎不同提取物的抗炎作用。联用灰色关联分析（GRA）和偏最小二乘回归分析（PLSR）2种方法建立其谱效关系；运用分子对接技术预测川芎有效成分的作用靶点，并利用京都基因与基因组百科全书（KEGG）对其进行通路分析，阐释川芎的抗炎作用机制。结果：川芎的95%乙醇提取物，75%乙醇提取物，50%乙醇提取物，25%乙醇提取物，结晶，石油醚萃取物和三氯甲烷萃取物对炎症细胞均具有抗炎的作用，其中川芎95%乙醇提取物的抗炎效果最为显著。确定了3种具有抗炎药效的成分（洋川芎内酯A，Z-藁本内酯和新蛇床内酯）；Z-藁本内酯可能通过环氧合酶-2（COX-2），细胞外调节蛋白激酶2（ERK2），蛋白激酶C （PKC），Janus激酶1（JAK1），JAK2，JAK3，核转录因子-кB （NF-кB）抑制蛋白激酶β（IKKβ），肿瘤坏死因子-α（TNF-α）阻碍炎症信号传递，影响下游蛋白的表达，发挥抗炎作用；洋川芎内酯A和新蛇床内酯可能通过COX-2，ERK2，PKC，磷酸酰肌醇3-激酶α（PI3K-α），PI3K-γ，JAK1，JAK2，JAK3，IKKβ，TNF-α阻碍炎症信号传递，影响下游蛋白的表达，发挥抗炎作用。结论：川芎中3种具有抗炎药效的成分为洋川芎内酯A，Z-藁本内酯和新蛇床内酯，通过不同的靶点阻碍炎症的信号传递，影响下游蛋白的表达，从而发挥抗炎作用，揭示了川芎抗炎的主要活性成分、靶点及作用机制，为深入探讨其药理学作用提供了参考。

Abstract

Objective: To study on the spectrum-effect relationship between UPLC fingerprint and anti-inflammatory of different extracts of Chuanxiong Rhizoma

in order to determine the active ingredients of this herb and describe its network regulatory mechanism. Method: UPLC-Q-TOF/MS was used to analyze the components in 8 different extracts of Chuanxiong Rhizoma.The anti-inflammatory effect of extracts was investigated by human bronchial epithelial cells.The spectrum-effect relationship was established by grey correlation analysis(GRA) and partial least squares repression analysis(PLSR).Molecular docking technology was adopted to predict the targets of active components in Chuanxiong Rhizoma

and Kyoto Encyclopedia of Genes and Genomes(KEGG) database was employed to analyze the pathways in order to explain the anti-inflammatory mechanism of this herb. Result: The 95% ethanol extract

75% ethanol extract

50% ethanol extract

25% ethanol extract

crystal

ligarine extract and chloroform extract all had anti-inflammatory effect on inflammatory cells

and 95% ethanol extract of Chuanxiong Rhizoma was the strongest.Three anti-inflammatory components were senkyunolide A

Z-ligustilide and neocnidilide.Z-ligustilide may inhibit the expression of downstream proteins by inhibiting the signal transduction to play anti-inflammatory effect through cyclooxygenase-2(COX-2)

extracellular regulated protein kinase 2(EKR2)

protein kinase C(PKC)

Janus kinase 1(JAK1)

JAK2

JAK3

nuclear transcription factor-кB inhibitory protein kinase β(IKKβ) and tumor necrosis factor-α(TNF-α);but signal channels of senkyunolide A and neocnidilide were COX-2

EKR2

PKC

phosphatidylinositol 3-kinase-α(PI3K-α)

PI3K-γ

JAK1

JAK2

JAK3

IKKβ and TNF-α. Conclusion: Senkyunolide A

Z-ligustilide and neocnidilide are active components with anti-inflammatory effect in Chuanxiong Rhizoma.They may inhibit the expression of downstream proteins by inhibiting the signal transduction to play anti-inflammatory effect through different targets

which reveals the main active components

targets and mechanism of Chuanxiong Rhizoma and provides a reference for further study of its pharmacological role.

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