Anti-inflammatory effects of rhynchophylline and isorhynchophylline in mouse N9 microglial cells and the molecular mechanism

被引：105

作者：

Yuan, Dan ^{[1
]}

Ma, Bin ^{[1
]}

Yang, Jing-yu ^{[2
]}

Xie, Yuan-yuan ^{[1
]}

Wang, Li ^{[2
]}

Zhang, Li-jia ^{[2
]}

Kano, Yoshihiro ^{[1
]}

Wu, Chun-fu ^{[2
]}

机构：

[1] Shenyang Pharmaceut Univ, Dept Tradit Chinese Med, Shenyang 110016, Peoples R China

[2] Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2009年 / 9卷 / 13-14期

关键词：

Anti-inflammation; Oxindole alkaloid; iNOS; TNF-alpha and IL-1 beta; Signaling pathway; Microglia; LIPOPOLYSACCHARIDE-ACTIVATED MICROGLIA; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; UNCARIA-RHYNCHOPHYLLA; NEURONAL APOPTOSIS; PARKINSONS-DISEASE; TERMINAL KINASE; CHOTO-SAN; CHANNELS; BRAIN;

D O I：

10.1016/j.intimp.2009.09.010

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Excessive production of nitric oxide (NO) and proinflammatory cytokines from activated microglia contributes to human neurodegenerative disorders. Our previous study demonstrated the potent inhibition of lipopolysaccharide (LPS)-induced NO production in rat primary microglial cells by rhynchophylline (RIN) and isorhynchophylline (IRN), a pair of isomeric alkaloids of Uncaria rhynchophylla (Miq.) jacks. that has been used in China for centuries as a "cognitive enhancer" as well as to treat strokes. We further investigated whether RIN and IRN effectively suppress release of proinflammatory cytokines in LPS-activated microglial cells and the underling molecular mechanism for the inhibition of microglial activation. RIN and IRN concentration-dependently attenuated LPS-induced production of proinflammatory cytokines such as TNF-alpha and IL-1 beta as well as NO in mouse N9 microglial cells, with IRN showing more potent inhibition of microglial activation. The western blotting analysis indicated that the potential molecular mechanism for RIN or IRN-mediated attenuation was implicated in suppressions of iNOS protein level, phosphorylation of ERK and p38 MAPKs, and degradation Of I kappa B alpha. In addition, the differential regulation of the three signaling pathways by two isomers was shown. Our results suggest that RIN and IRN may be effective therapeutic candidates for use in the treatment of neurodegenerative diseases accompanied by microglial activation. (C) 2009 Elsevier B.V. All rights reserved.

引用

页码：1549 / 1554

页数：6

共 46 条

[1]

[Anonymous], J TRADIT MED

[2] BACTERIAL-ENDOTOXIN INDUCES [CA2+]I TRANSIENTS AND CHANGES THE ORGANIZATION OF ACTIN IN MICROGLIA [J].

BADER, MF ;

TAUPENOT, L ;

ULRICH, G ;

AUNIS, D ;

CIESIELSKITRESKA, J .

GLIA, 1994, 11 (04) :336-344

[3]

Bal-Price A, 2001, J NEUROSCI, V21, P6480

[4] Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E [J].

Barger, SW ;

Harmon, AD .

NATURE, 1997, 388 (6645) :878-881

[5]

Bensky D., 1999, Chinese Medicine: Materia Medica, P423

[6] Adenovirus infection induces microglial activation: involvement of mitogen-activated protein kinase pathways [J].

Bhat, NR ;

Fan, F .

BRAIN RESEARCH, 2002, 948 (1-2) :93-101

[7] Resveratrol inhibits nitric oxide and TNF-α production by lipopolysaccharide-activated microglia [J].

Bi, XL ;

Yang, JY ;

Dong, YX ;

Wang, JM ;

Cui, YH ;

Ikeshima, T ;

Zhao, YQ ;

Wu, CF .

INTERNATIONAL IMMUNOPHARMACOLOGY, 2005, 5 (01) :185-193

[8] Regulation of c-Jun-NH2 terminal kinase and extracellular-signal regulated kinase in human platelets [J].

Bugaud, F ;

Nadal-Wollbold, F ;

Lévy-Toledano, S ;

Rosa, JP ;

Bryckaert, M .

BLOOD, 1999, 94 (11) :3800-3805

[9] Cholesterol oxides induce programmed cell death in microglial cells [J].

Chang, JY ;

Chavis, JA ;

Liu, LZ ;

Drew, PD .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 249 (03) :817-821

[10]

CHAO CC, 1992, J IMMUNOL, V149, P2736

← 1 2 3 4 5 →