7,3′-dimethoxy hesperetin inhibits inflammation by inducing synovial apoptosis in rats with adjuvant-induced arthritis

被引：48

作者：

Li, Rong ^{[1
,2
]}

Cai, Li ^{[3
]}

Xie, Xue-feng ^{[1
,2
]}

Peng, Lei ^{[1
,2
]}

Wu, Ting-ni ^{[1
,2
]}

Li, Jun ^{[1
,2
]}

机构：

[1] Anhui Med Univ, Sch Pharm, Dept Med Chem, Hefei 230032, Peoples R China

[2] Key Lab Bioact Nat Med Anhui Prov, Dept Med Chem, Hefei, Peoples R China

[3] Anhui Med Univ, Sch Basic Med, Dept Pathol, Hefei 230032, Peoples R China

来源：

IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY | 2013年 / 35卷 / 01期

基金：

中国国家自然科学基金;

关键词：

7,3 '-dimethoxy hesperetin; adjuvant arthritis; inflammation; synovial apoptosis; Bcl-2; COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; JOINT DESTRUCTION; HESPERIDIN; MECHANISMS; EXPRESSION; CELLS; MICE; PATHOGENESIS; CONTRIBUTES;

D O I：

10.3109/08923973.2012.723010

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Rheumatoid arthritis (RA) is an autoimmune disease characterized by pronounced inflammation and excessive synovial hyperplasia within affected joint. We previously reported 7, 3'-dimethoxy hesperetin (DMHP) as a highly anti-inflammatory active derivative of hesperidin showed apparent pro-apoptotic effect in vitro on fibroblast-like synoviocytes of rats with adjuvant arthritis (AA), an animal model of RA. Here, we investigated the therapeutic effects of DMHP on inflammation and synovial apoptosis in rats with AA in vivo. Paw swelling, arthritis index, TNF-alpha and IL-1 beta serum levels were measured to evaluate the effect of DMHP on inflammation in AA rats. DNA ladder detection and TUNEL assay were used to investigate the pro-apoptotic effect of DMHP on synovial apoptosis in vivo. Bcl-2, Bax mRNA and protein expressions in synovium were determined by real-time Q-PCR and western blot, respectively. We found DMHP inhibited secondary hind paw swelling and arthritis index, and decreased TNF-alpha and IL-1 beta serum levels in AA rats. Typical DNA ladder formation was found in DNA extraction of synovium from DMHP treated groups. The number of apoptotic synovial cells was elevated with DMHP treatment in TUNEL assay. DMHP markedly decreased Bcl-2 expression whereas increased Bax expression in synovium of AA rats at both transcription and protein levels. Moreover, DMHP treatment on AA rats significantly decreased the protein ratio of Bcl-2/Bax in synovium. In conclusion, DMHP has an apparent therapeutic effect on inflammation in rats with AA. Mechanisms of this effect are partly related to induction of synovial apoptosis through modulation of Bcl-2 and Bax expression.

引用

页码：139 / 146

页数：8

共 41 条

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Flavanone absorption after naringin, hesperidin, and citrus administration [J].