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Anti-arthritic effect of GN1, a novel synthetic analog of glucosamine, in the collagen-induced arthritis model in rats

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Abstract

Objective

Glucosamine is a naturally occurring amino monosaccharide that maintains the elasticity and strength of the cartilage tissues. It has been used to treat osteoarthritis in humans; however, in severe conditions of inflammation and pain, glucosamine alone is not enough, and it is important to improve its biological activity. Our research group has recently taken an interest in the synthetic manipulation of amino sugars to develop some efficient pharmacophores, e.g., β-d-glucosamine, to combat rheumatoid arthritis, and tested its anti-arthritic effects in the collagen-induced arthritis (CIA) model in rats.

Methods

Arthritis was induced in female Sprague–Dawley rats by multiple intradermal injections of bovine type II collagen and challenged again with the same antigen preparation 7 days later. Arthritis was evaluated by arthritic score, body weight loss, paw volume measurement, and histological changes.

Results

The animals in the arthritic control group showed a gradual decrease in their body weight and concurrent increase in the paw volumes compared to the normal control group. In contrast, increased hind paw swelling was significantly suppressed with no further noticeable reduction in body weight in the glucosamine (p < 0.05) and GN1-treated (p < 0.02) arthritic animals. Histopathological evaluation of isolated knee joints by grading system and classification of the stages in arthritic lesion development revealed suppression of the inflammatory changes in the GN1-treated animals. Moreover, both the pro-inflammatory markers C-reactive protein (CRP) and low-density lipoprotein (LDL) levels were found to be significantly decreased in animals treated with GN1 (p < 0.03 for CRP and p < 0.05 for LDL) compared to the arthritic control group.

Conclusion

These results suggest that GN1 has both anti-arthritic and anti-inflammatory properties. Its effects in the CIA model suggest that it could be useful in the treatment of rheumatoid arthritis.

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Abbreviations

CIA:

Collagen-induced arthritis

CRP:

C-reactive protein

LDL and HDL:

Low-density lipoprotein and high-density lipoprotein

TNF-α:

Tumor necrosis factor-α

NSAID:

Non-steroidal anti-inflammatory drug

CII:

Bovine type II collagen

IFA:

Incomplete Freund’s adjuvant

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Authors and Affiliations

  1. Pharmacology Unit, Lab. # 314, H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Huma Jawed, Shazia Anjum, Shahid I. Awan & Shabana U. Simjee

  2. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Shabana U. Simjee

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  1. Huma Jawed
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  2. Shazia Anjum
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Correspondence to Shabana U. Simjee.

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Jawed, H., Anjum, S., Awan, S.I. et al. Anti-arthritic effect of GN1, a novel synthetic analog of glucosamine, in the collagen-induced arthritis model in rats. Inflamm. Res. 60, 1113–1120 (2011). https://doi.org/10.1007/s00011-011-0375-9

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