Glycyrrhetinic acid inhibits ICAM-1 expression via blocking JNK and NF-κB pathways in TNF-α-activated endothelial cells

被引:62
作者
Chang, Ying-ling [1 ]
Chen, Chien-lin [1 ,2 ]
Kuo, Chao-lin [3 ]
Chen, Bor-chyuan [4 ]
You, Jyh-sheng [1 ,2 ]
机构
[1] Chang Gung Univ, Sch Tradit Chinese Med, Tao Yuan, Taiwan
[2] Chang Gung Mem Hosp, Ctr Tradit Chinese Med, Tao Yuan, Taiwan
[3] China Med Univ, Coll Pharm, Sch Chinese Med Resources, Taichung, Taiwan
[4] Buddist Tzuchi Dalin Gen Hosp, Dept Chinese Med, Chiayi, Taiwan
关键词
glycyrrhetinic acid; intercellular adhesion molecule 1; tumor necrosis factor alpha; nuclear factor-kappa B; mitogen-activated protein kinases; TUMOR-NECROSIS-FACTOR; ADHESION MOLECULE-1 EXPRESSION; LEUKOCYTE ADHESION; RAT HEPATOCYTES; IN-VITRO; KINASE; GLYCYRRHIZIN; AP-1; CHEMOKINES; VCAM-1;
D O I
10.1038/aps.2010.34
中图分类号
O6 [化学];
学科分类号
070301 [无机化学];
摘要
Aim: To investigate the effects of glycyrrhetinic acid (GA), an active component extracted from the root of Glycyrrhizae glabra, on the expression of intercellular adhesion molecule-1 (ICAM-1) in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVEC). Methods: ICAM-1 mRNA and protein levels were detected using RT-PCR and cell enzyme-linked immunosorbent assays. The adherence of human monocytic THP-1 cells labeled with [3H] thymidine to HUVEC was determined by counting radioactivity with a scintillation counter. The activation of mitogen-activated protein kinases as well as the degradation of I kappa B and nuclear factor-kappa B (NF-kappa B) or phospho-cJun in the nucleus were detected by western blots. NF-kappa B binding activity was detected using electrophoretic mobility shift assay. Results: GA (50 and 100 mmol/L) significantly inhibits TNF-alpha-induced ICAM-1 mRNA and protein expressions, as well as THP-1 cell adhesiveness in HUVEC. GA selectively inhibited TNF-alpha-activated signal pathway of c-Jun N-terminal kinase (JNK), without affecting extracellular signal-regulated kinase 1/2 and p38. Furthermore, GA apparently inhibited I kappa B/NF-kappa B signaling system by preventing I kappa B degradation, NF-kappa B translocation, and NF-kappa B/DNA binding activity. Finally, pretreatment with GA or the inhibitors of NF-kappa B, JNK, and p38 reduced the ICAM-1 protein expression induced by TNF-alpha. Conclusion: GA inhibits TNF-alpha-stimulated ICAM-1 expression, leading to a decrease in adherent monocytes to HUVEC. This inhibition is attributed to GA interruption of both JNK/c-Jun and I kappa B/NF-kappa B signaling pathways, which decrease activator protein-1 (AP-1) and NF-kappa B mediated ICAM-1 expressions. The results suggest that GA may provide a beneficial effect in treating vascular diseases associated with inflammation, such as atherosclerosis.
引用
收藏
页码:546 / 553
页数:8
相关论文
共 33 条
[1]
Synthesis and in Vitro antioxidant activity of glycyrrhetinic acid derivatives tested with the cytochrome P450/NADPH system [J].
Ablise, M ;
Leininger-Muller, B ;
Wong, CD ;
Siest, G ;
Loppinet, V ;
Visvikis, S .
CHEMICAL & PHARMACEUTICAL BULLETIN, 2004, 52 (12) :1436-1439
[2]
The NF-kappa B and I kappa B proteins: New discoveries and insights [J].
Baldwin, AS .
ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 :649-683
[3]
Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion [J].
Brand, K ;
Page, S ;
Rogler, G ;
Bartsch, A ;
Brandl, R ;
Knuechel, R ;
Page, M ;
Kaltschmidt, C ;
Baeuerle, PA ;
Neumeier, D .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (07) :1715-1722
[4]
Chang YL, 2001, MOL PHARMACOL, V60, P507
[5]
ENDOTHELIAL EXPRESSION OF A MONONUCLEAR LEUKOCYTE ADHESION MOLECULE DURING ATHEROGENESIS [J].
CYBULSKY, MI ;
GIMBRONE, MA .
SCIENCE, 1991, 251 (4995) :788-791
[6]
THE EXPRESSION OF THE ADHESION MOLECULES ICAM-1, VCAM-1, PECAM, AND E-SELECTIN IN HUMAN ATHEROSCLEROSIS [J].
DAVIES, MJ ;
GORDON, JL ;
GEARING, AJH ;
PIGOTT, R ;
WOOLF, N ;
KATZ, D ;
KYRIAKOPOULOS, A .
JOURNAL OF PATHOLOGY, 1993, 171 (03) :223-229
[7]
Activation of Jun N-terminal kinase/stress-activated protein kinase pathway by tumor necrosis factor α leads to intercellular adhesion molecule-1 expression [J].
De Cesaris, P ;
Starace, D ;
Starace, G ;
Filippini, A ;
Stefanini, M ;
Ziparo, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (41) :28978-28982
[8]
Role of neutrophil NADPH oxidase in the mechanism of tumor necrosis factor-α-induced NF-κB activation and intercellular adhesion molecule-1 expression in endothelial cells [J].
Fan, J ;
Frey, RS ;
Rahman, A ;
Malik, AB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (05) :3404-3411
[9]
Antiatherosclerotic effects of licorice extract supplementation on hypercholesterolemic patients: Increased resistance of LDL to atherogenic modifications, reduced plasma lipid levels, and decreased systolic blood pressure [J].
Fuhrman, B ;
Volkova, N ;
Kaplan, M ;
Presser, D ;
Attias, J ;
Hayek, T ;
Aviram, M .
NUTRITION, 2002, 18 (03) :268-273
[10]
Licorice compounds glycyrrhizin and 18β-glycyrrhetinic acid are potent modulators of bile acid-induced cytotoxicity in rat hepatocytes [J].
Gumpricht, E ;
Dahl, R ;
Devereaux, MW ;
Sokol, RJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (11) :10556-10563