title: Grape seed proanthocyanidin extract (GSPE) attenuates collagen-induced arthritis.
abstract: To examine whether grape seed proanthocyanidin extract (GSPE) which is known to act as an antioxidant has therapeutic effect on collagen-induced arthritis (CIA) in mice, an animal model of rheumatoid arthritis. Mice were treated with an intraperitoneal injection of GSPE (10, 50, or 100 mg/kg) or saline. Clinical, histological, and biochemical parameters were assessed. The effects of GSPE on osteoclastogenesis were determined by tartrate-resistant acid phosphatase (TRAP) staining of the inflamed joints and bone-marrow cells cultured with the receptor activator of nuclear factor B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Intracellular levels of hydrogen peroxide were determined using carboxy-dichlorodihydrofluorescein diacetate. GSPE treatment significantly attenuated the severity of CIA in a dose-dependent manner and reduced the histology scores for synovial inflammation, cartilage erosion, bone erosion, and the number of TRAP+ osteoclasts. GSPE treatment significantly reduced the numbers of tumor necrosis factor alpha (TNF-alpha)- or interleukin 17 (IL-17)-producing cells in the synovial tissue and the spontaneous production of TNF-alpha and IL-17 by splenocytes compared with those in the control mice. The serum levels of type-II-collagen-specific IgG2a and plasma levels of 8-isoprostane in the GSPE-treated mice were significantly lower than those in the control mice. GSPE dose-dependently suppressed osteoclastogenesis in vitro. GSPE significantly reduced hydrogen peroxide production by anti-CD3-monoclonal-antibody-stimulated CD4+ splenocytes. These results indicate that intraperitoneal injection of GSPE attenuated CIA in mice. GSPE may be useful in the treatment of rheumatoid arthritis.
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Heo
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Park
authors.forename: Hye-Jwa
authors.initials: HJ
authors.lastname: Oh
authors.forename: Jin-Sil
authors.initials: JS
authors.lastname: Park
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Woo
authors.forename: Ji-Hyeon
authors.initials: JH
authors.lastname: Ju
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
authors.forename: Jun-Ki
authors.initials: JK
authors.lastname: Min
mesh_terms: D000135:Acid Phosphatase / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000843:Ankle Joint / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000906:Antibodies / Q000097:blood / Q000187:drug effects; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002478:Cells, Cultured; D024043:Collagen Type II / Q000494:pharmacology; D004195:Disease Models, Animal; D056604:Grape Seed Extract; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism; D028421:Isoprostanes / Q000037:antagonists & inhibitors / Q000097:blood; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA; D010010:Osteoclasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000627:therapeutic use*; D044945:Proanthocyanidins / Q000008:administration & dosage / Q000627:therapeutic use*; D053245:RANK Ligand / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology
chemical_list: D000906:Antibodies; D024043:Collagen Type II; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D020381:Interleukin-17; D007527:Isoenzymes; D028421:Isoprostanes; D010936:Plant Extracts; D044945:Proanthocyanidins; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D006861:Hydrogen Peroxide; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase