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ANTI-INFLAMMATORY EFFECTS OF STANDARDISED ETHANOLIC EXTRACT FROM THE RIND OF THE NEPHELIUM LAPPACEUM FRUIT IN A RAT MODEL OF RHEUMATOID ARTHRITIS

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Abstract
Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease, where the host immune system attacks the joints. This study used collagen-induced arthritis (CIA) animal model to study the effect of plant-derived antioxidants as the plant-derived antioxidants are known to reduce inflammatory responses in CIA. The aim of the study was to assess the efficacy of ethanol extract from the rind of the rambutan (Nephelium lappaceum) fruit to treat CIA in dark agouti (DA) female rats. Arthritis was induced in DA rats by injecting them with a commercial preparation of collagen from chicken sternal cartilage (4 mg/kg) mixed in complete Freund's adjuvant (CFA). Changes in body weight and joint thickness were monitored every five days from day 0 to 50 of the study. When the signs of arthritis were visible on day 25, the arthritic rats were fed with 300 mg/kg glucosamine or the standardised ethanolic extract (100 or 200 mg/kg) from the rind of the N. lappaceum fruit for 25 days (i.e. until day 50). At autopsy, the sera collected from the animals were tested for C-reactive protein (CRP) and the joints were harvested for histopathology and real-time polymerase chain reaction (qPCR) analysis. iii Both concentrations (100 and 200 mg/kg) of the ethanolic extracts from the rind of the N. lappaceum significantly reduced the arthritis-induced changes in body weight (p<0.05) and paw oedema (p<0.05). There was a significant reduction in the plasma CRP levels (p<0.05) in the treated groups. In addition, a significant reduction (p<0.05) in the arthritis-induced histopathological changes was observed after treatment with the N. lappaceum rind extract. Immunohistochemistry analysis showed that treatment with the N. lappaceum extracts had dose-dependent effects on matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) expression in the joints. There was a minimum of two-fold down regulation (p<0.05) of the TNF-α, COX-2 and NF-κB genes in the joints from arthritic rats treated with the N. lappaceum rind extracts (200 and 100 mg/kg) or glucosamine (300 mg/kg). Treatment with the N. lappaceum rind extracts or glucosamine appear to show regression of RA in the arthritic rats. In conclusion, oral supplementation of standardised ethanolic extract of N. lappaceum rind significantly suppressed pathophysiological, biochemical and histopathological changes induced by collagen administration in the CIA rats. Supplementation with the N. lappaceum extract may be beneficial in preventing the tissue damage and inflammatory conditions in arthritis.
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Arthritis, Rheumatoid, Anti-Inflammatory Agents, Arthritis, Experimental
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