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Suppressive Effects of the Standardized Extract of Phyllanthus amarus on Type II Collagen-induced Rheumatoid Arthritis in Sprague Dawley Rats

[ Vol. 19 , Issue. 14 ]


Javaid Alam, Ibrahim Jantan*, Endang Kumolosasi, Mohd A. Nafiah and Muhammed A. Mesaik   Pages 1156 - 1169 ( 14 )


Background: Standardized extract of Phyllanthus amarus has been shown to possess inhibitory effects on cellular and humoral immune responses in Wistar-Kyoto rats and Balb/c mice.

Objective: In the present study, the standardized extract of P. amarus was investigated for its suppressive effects on type II collagen-induced rheumatoid arthritis (TCIA) in Sprague Dawley rats.

Method: The major components of the extracts, lignans and phenolic compounds were analysed by using a validated reversed phase HPLC and LC-MS/MS. A rheumatoid arthritis rat model was induced by administering a bovine type II collagen emulsion subcutaneously at the base of tail, on day 0 and 7 of the experiment. Effects of the extract on severity assessment, changes in the hind paw volume, bone mineral density, body weight and body temperature were measured. Concentrations of cytokines (TNF-α, IL-1β, IL-1α, IL-6) released, matrix metalloproteinases (MMP-1, MMP-3 MMP-9) and their inhibitor (TIMP-1), haematological and biochemical changes were also measured. ELISA was used to measure the cytokines and proteinases in the rat serum and synovial fluid according to manufacturer's instructions.

Results: The extract dose-dependently modulated the progression in physical parameters (i.e. decrease in body weight, increase in body temperature, reduced hind paw volume, reduced the severity of arthritis), bone mineral density, haematological and biochemical perturbations, serum cytokines production and levels of matrix metalloproteinases and their inhibitor in the synovial fluid. Histopathological examination of the knee joint also revealed that the extract effectively reduced synovitis, pannus formation, bone resorption and cartilage destruction.

Conclusion: The results suggest that the oral administration of a standardized extract of P. amarus was able to suppress the humoral and cellular immune responses to type II collagen, resulting in the reduction of the development of TCIA in the rats.


Phyllanthus amarus, rheumatoid arthritis, pro-inflammatory cytokines, type II collagen-induced arthritis, immune response, metalloproteinases.


Drug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, School of Pharmacy, Taylor's University, Lakeside Campus, 47500 Subang Jaya, Selangor, Drug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Department of Chemistry, Faculty of Science and Mathematics, Universiti Pendidikan Sultan Idris, 35900 Tanjung Malim, Perak, Faculty of Medicine,University of Tabuk, Tabuk 71491

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