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细叶远志皂苷通过抑制PI3K/AKT/NF-κB信号通路预防白细胞介素-1β诱导的人骨关节炎软骨细胞炎症。

Tenuigenin Prevents IL-1β-induced Inflammation in Human Osteoarthritis Chondrocytes by Suppressing PI3K/AKT/NF-κB Signaling Pathway.

作者信息

Wang Chunlei, Zeng Lihong, Zhang Tao, Liu Jiakun, Wang Wenbo

机构信息

Department of Orthopedics, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.

Harbin Children Hospital, Harbin, 150010, China.

出版信息

Inflammation. 2016 Apr;39(2):807-12. doi: 10.1007/s10753-016-0309-3.


DOI:10.1007/s10753-016-0309-3
PMID:26846886
Abstract

Tenuigenin (TEN), the main active component of Polygala tenuifolia, has been reported to have anti-inflammatory effects. However, the effects of TEN on IL-1β-stimulated osteoarthritis chondrocytes have not been reported. The purpose of this study was to investigate the anti-inflammatory effects and mechanism of TEN on IL-1β-stimulated human osteoarthritis chondrocytes. Human osteoarthritis chondrocytes were pretreated with or without TEN for 1 h and then stimulated with IL-1β. The production of NO and PGE2 were detected by the Griess reagent and ELISA. The expression of NF-κB and MAPKs (p38, JNK, ERK) were measured by Western blot analysis. The production of MMP-1, MMP3, and MMP13 were measured by ELISA. The results showed that treatment of TEN significantly inhibited IL-1β-induced NO and PGE2 production. TEN also suppressed IL-1β-induced MMP-1, MMP3, and MMP13 expression. Furthermore, TEN was found to inhibit IL-1β-induced NF-κB activation, PI3K, and AKT phosphorylation. In conclusion, these results suggest that TEN inhibits IL-1β-induced inflammation in human osteoarthritis chondrocytes by inhibiting PI3K/AKT/NF-κB signaling pathway.

摘要

远志皂苷元(TEN)是远志的主要活性成分,据报道具有抗炎作用。然而,TEN对白细胞介素-1β(IL-1β)刺激的骨关节炎软骨细胞的影响尚未见报道。本研究的目的是探讨TEN对IL-1β刺激的人骨关节炎软骨细胞的抗炎作用及其机制。将人骨关节炎软骨细胞在有或无TEN的情况下预处理1小时,然后用IL-1β刺激。采用Griess试剂和酶联免疫吸附测定(ELISA)检测一氧化氮(NO)和前列腺素E2(PGE2)的产生。通过蛋白质免疫印迹分析检测核因子κB(NF-κB)和丝裂原活化蛋白激酶(MAPKs,包括p38、c-Jun氨基末端激酶(JNK)、细胞外信号调节激酶(ERK))的表达。采用ELISA检测基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-3(MMP3)和基质金属蛋白酶-13(MMP13)的产生。结果表明,TEN处理可显著抑制IL-1β诱导的NO和PGE2产生。TEN还可抑制IL-1β诱导的MMP-1、MMP3和MMP13表达。此外,发现TEN可抑制IL-1β诱导的NF-κB活化、磷脂酰肌醇-3激酶(PI3K)和蛋白激酶B(AKT)磷酸化。总之,这些结果表明,TEN通过抑制PI3K/AKT/NF-κB信号通路抑制IL-1β诱导的人骨关节炎软骨细胞炎症。

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本文引用的文献

[1]
Schisandrae Fructus Inhibits IL-1β-Induced Matrix Metalloproteinases and Inflammatory Mediators Production in SW1353 Human Chondrocytes by Suppressing NF-κB and MAPK Activation.

Drug Dev Res. 2015-12

[2]
Tenuigenin ameliorates acute lung injury by inhibiting NF-κB and MAPK signalling pathways.

Respir Physiol Neurobiol. 2015-9-15

[3]
Tenuigenin ameliorates learning and memory impairments induced by ovariectomy.

Physiol Behav. 2013-5-17

[4]
Tenuigenin protects dopaminergic neurons from inflammation-mediated damage induced by the lipopolysaccharide.

CNS Neurosci Ther. 2012-7

[5]
Tenuigenin promotes proliferation and differentiation of hippocampal neural stem cells.

Neurochem Res. 2011-12-18

[6]
Neuroprotective effects of tenuigenin in a SH-SY5Y cell model with 6-OHDA-induced injury.

Neurosci Lett. 2011-4-25

[7]
Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients.

Clin Exp Rheumatol. 2011-2-23

[8]
NF-κB, inflammation, and metabolic disease.

Cell Metab. 2011-1-5

[9]
Role of proinflammatory cytokines in the pathophysiology of osteoarthritis.

Nat Rev Rheumatol. 2010-11-30

[10]
Selenomethionine inhibits IL-1β inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) expression in primary human chondrocytes.

Osteoarthritis Cartilage. 2010-10-28

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