Anti-arthritic activity of synthesized chondroitin sulfate E hexasaccharide

Abstract

The purpose of this study was to investigate the anti-arthritic effects of synthesized chondroitin sulfate E hexasaccharide (sCSE-6, CAS 866407-73-0), using a type II collagen-induced arthritis model in mice. sCSE-6 was administered subcutaneously on a daily basis to type II collagen (CII) -sensitized mice from day 0 to day 55. The severity of arthritis, as well as the immunohistological features of the arthritic mice, were analyzed. sCSE-6 inhibited the course of arthritis and restored the body weight loss of CII-im-munized mice. An immunohistological analysis showed that bone/cartilage destruction in the arthritic mice was significantly attenuated by sCSE-6 treatment, with a marginal inhibition of synovial inflammation also observed. The beneficial effect of sCSE-6 on bone destruction, which is the most important factor in preventing arthritis, is particularly noteworthy. In summary, sCSE-6 inhibited arthritis and helped to prevent bone and cartilage destruction in a type II collagen-induced arthritis model in mice. The findings indicated that CSE oligosaccharides might be a novel potential therapeutic tool for rheumatoid arthritis.

Key words

Bone destruction - CAS 866407-73-0 - Chondroitin sulfate E - Collagen-induced arthritis - Oligosaccharide

• References

• 1 Kawashima H, Atarashi K, Hirose M, Hirose J, Yamada S, Sugahara K et al Oversulfated chondroitin/dermatan sulfates containing GlcAßl/IdoAαl-3GalNAc (4,6-O-disulfate) interact with L- and P-selectin and chemokines. J Biol Chem. 2002; 277 (15) 12921-30
• 2 Tully SE, Mabon R, Gama CI, Tsai SM, Liu X, Hsieh-Wilson LC. A chondroitin sulfate small molecule that stimulates neuronal growth. J Am Chem Soc. 2004; 126 (25) 7736-7
• 3 Tully SE, Rawat M, Hsieh-Wilson LC. Discovery of a TNF-α antagonist using chondroitin sulfate microarrays. J Am Chem Soc. 128 (24) 7740-1
• 4 Sotogaku N, Tully SE, Gama CI, Higashi H, Tanaka M, Hsieh-Wilson LC et al Activation of phospholipase C pathways by a synthetic chondroitin sulfate-E tetrasaccharide promotes neurite outgrowth of dopaminergic neurons. J Neurochem. 2007; 103 (2) 749-60
• 5 Tamura J, Tokuyoshi M. Synthesis of chondroitin sulfate E hexasaccharide in the repeating region by an effective elongation strategy toward longer chondroitin oligosaccharide. Biosci Biotechnol Biochem. 2004; 68 (12) 2436-43
• 6 Tamura J, Nakada Y, Taniguchi K, Yamane M. Synthesis of chondroitin sulfate E octasaccharide in a repeating region involving an acetamide auxiliary. Carbohydr Res. 2008; 343 (l) 39-47
• 7 Wood KM, Wusteman FS, Curtis CG. The degradation of intravenously injected chondroitin 4-sulphate in the rat. Biochem J. 1973; 134 (4) 1009-13
• 8 Ronca F, Palmieri L, Panicucci P, Ronca G. Anti-inflammatory activity of chondroitin sulfate. Osteoarthritis Cartilage. 1998; 6: 14-21
• 9 Cohen M, Wolfe R, Mai T, Lewis D. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. J Rheumatology. 2003; 30 (3) 523-8
• 10 Campo GM, Avenoso A, Campo S, D’Ascola A, Traina P, Calatroni A. Chondroitin-4-sulphate inhibits NF-kB translocation and caspase activation in collagen-induced arthritis in mice. Osteoarthritis Cartilage. 2008; 16 (12) 1474-93
• 11 Volpi N. Oral absorption and bioavailability of ichthyic origin chondroitin sulfate in healthy male volunteers. Osteoarthritis Cartilage 2. 2003; 11 (6) 433-41
• 12 Kusano S, Ootani A, Sakai S, Igarashi N, Takeguchi A, Toyoda H et al HPLC determination of chondrosine in mouse blood plasma after intravenous or oral dose. Biol Pharm Bull. 2007; 30 (8) 1365-8
• 13 Sugahara KN, Hirata T, Tanaka T, Ogino S, Takeda M, Terasawa H et al Chondroitin sulfate E fragments enhance CD44 cleavage and CD44-dependent motility in tumor cells. Cancer Res. 2008; 68 (17) 7191-9