Anti-inflammatory effects and pharmacokinetics study of geniposide on rats with adjuvant arthritis

被引：68
作者：
Chen, Jin-Yun [1 ]
Wu, Hong [1 ]
Li, Hui [1 ]
Hu, Shun-Li [1 ]
Dai, Miao-miao [1 ]
Chen, Jian [1 ]
机构：
[1] Anhui Univ Chinese Med, Coll Pharm, Key Lab Modernized Chinese Med Anhui Prov, Hefei 230031, Anhui, Peoples R China
来源：
INTERNATIONAL IMMUNOPHARMACOLOGY | 2015年 / 24卷 / 01期
基金：
中国国家自然科学基金;
关键词：
Inflammation; Fibroblast-like synoviocytes; Pharmacokinetics; Geniposide; ACTIVATED PROTEIN-KINASE; GARDENIA-JASMINOIDES-ELLIS; RHEUMATOID-ARTHRITIS; SYNOVIAL TISSUE; MESSENGER-RNA; PATHWAY; CELLS; SYNOVIOCYTES; COMBINATION; RECEPTOR;
D O I：
10.1016/j.intimp.2014.11.017
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
The aim of this study was to explore the anti-inflammatory effects of Geniposide (GE), an iridoid glycoside compound extracted from Gardenia jasminoides Ellis (GJ) fruit in adjuvant-induced arthritis (AA) rats and its pharmacokinetic (PK) basis. AA was induced by injecting with Freund's complete adjuvant (FCA). Male SD rats were subjected to treatment with GE (30, 60 and 120 mg/kg) from day 17 to 24 after immunization. Fibroblast-like synoviocyte (FLS) proliferation was assessed by MTT. Interleukin (IL)-1, IL-6, TNF-alpha and IL-10 were determined using double-sandwich enzyme-linked immunosorbent assay (ELISA). Expression of p38 mitogen-activated protein kinases (p38MAPKs) related proteins in FLS was detected by Western blotting. PK profiles were simultaneously detected by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) in AA rat plasma after oral administration of GE on day 17 after immunization. As a result, GE promoted the recovery of arthritis and inhibited the colonic inflammation damage in AA rats by decreasing the expression level of TNF-alpha, IL-1 and IL-6, increasing the production of IL-10 and inhibiting the expression of phospho-p38 (p-p38) related proteins in FLS. PK parameters (AUC, C-max and t(1/2)) tended to be associated with dosage-related decreasing of efficacy index. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码：102 / 109
页数：8
相关论文
共 42 条
[1]   Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis [J].
Bartok, Beatrix ;
Firestein, Gary S. .
IMMUNOLOGICAL REVIEWS, 2010, 233 :233-255
[2]   The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumour necrosis factor [J].
Beyaert, R ;
Cuenda, A ;
VandenBerghe, W ;
Plaisance, S ;
Lee, JC ;
Haegeman, G ;
Cohen, P ;
Fiers, W .
EMBO JOURNAL, 1996, 15 (08) :1914-1923
[3]   Mechanisms and functions of p38 MAPK signalling [J].
Cuadrado, Ana ;
Nebreda, Angel R. .
BIOCHEMICAL JOURNAL, 2010, 429 :403-417
[4]   Effects and mechanisms of Geniposide on rats with adjuvant arthritis [J].
Dai, Miao-Miao ;
Wu, Hong ;
Li, Hui ;
Chen, Jian ;
Chen, Jin-Yun ;
Hu, Shun-Li ;
Shen, Chen .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2014, 20 (01) :46-53
[5]   Many cytokines are very useful therapeutic targets in disease [J].
Feldmann, Marc .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (11) :3533-3536
[6]   Geniposide, from Gardenia jasminoides Ellis, inhibits the inflammatory response in the primary mouse macrophages and mouse models [J].
Fu, Yunhe ;
Liu, Bo ;
Liu, Jinhua ;
Liu, Zhicheng ;
Liang, Dejie ;
Li, Fengyang ;
Li, Depeng ;
Cao, Yongguo ;
Zhang, Xichen ;
Zhang, Naisheng ;
Yang, Zhengtao .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2012, 14 (04) :792-798
[7]   Cytokine inhibitors in the treatment of rheumatoid arthritis [J].
Gabay, C .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2002, 2 (02) :135-149
[8]   Interleukin-6 Receptor Inhibition With Tocilizumab Reduces Disease Activity in Rheumatoid Arthritis With Inadequate Response to Disease-Modifying Antirheumatic Drugs The Tocilizumab in Combination With Traditional Disease-Modifying Antirheumatic Drug Therapy Study [J].
Genovese, Mark C. ;
McKay, James D. ;
Nasonov, Evgeny L. ;
Mysler, Eduardo F. ;
da Silva, Nilzio A. ;
Alecock, Emma ;
Woodworth, Thasia ;
Gomez-Rein, Juan J. .
ARTHRITIS AND RHEUMATISM, 2008, 58 (10) :2968-2980
[9]   Tumour necrosis factor activates the mitogen-activated protein kinases p38α and ERK in the synovial membrane in vivo [J].
Görtz, B ;
Hayer, S ;
Tuerck, B ;
Zwerina, J ;
Smolen, JS ;
Schett, G .
ARTHRITIS RESEARCH & THERAPY, 2005, 7 (05) :R1140-R1147
[10]   Antiinflammatory Functions of p38 in Mouse Models of Rheumatoid Arthritis Advantages of Targeting Upstream Kinases MKK-3 or MKK-6 [J].
Guma, Monica ;
Hammaker, Deepa ;
Topolewski, Katharyn ;
Corr, Maripat ;
Boyle, David L. ;
Karin, Michael ;
Firestein, Gary S. .
ARTHRITIS AND RHEUMATISM, 2012, 64 (09) :2887-2895
12345