Please use this identifier to cite or link to this item:
https://ptsldigital.ukm.my/jspui/handle/123456789/485643| Title: | Anti-inflammatory effect of standardized extract of phyllanthus amarus and its active compounds on human monocytic cell line (THP-1) and type-II collagen induced arthritis rat model |
| Authors: | Javaid Alam (P80766) |
| Supervisor: | Ibrahim Jantan, Prof. Dato. Dr. |
| Keywords: | Traditional medicine Rheumatoid Arthritis Inflammatory diseases Phyllanthus amarus Universiti Kebangsaan Malaysia -- Dissertations |
| Issue Date: | 14-Dec-2018 |
| Description: | Phyllanthus amarus Schum. & Thonn. is widely used in traditional medicine for the treatment of many inflammatory diseases including Rheumatoid Arthritis (RA). It has been shown to possess inhibitory effects on cellular and humoral immune responses in Wistar-Kyoto rats and Balb/c mice. In the present study, the 80% standardized ethanol extract of P. amarus and its major compounds were investigated for its antiinflammatory effect on human monocytic cell line (THP-1). and type-II collageninduced arthritis rat model. RA was induced by administering bovine type II collagen emulsion subcutaneously at the base of tail, on day 0 and day 7 of the experiment. P. amarus extract (100, 200, 400 mg/kg) and indomethacin (5 mg/kg) were given orally for 28 days. The extract was analysed by using a validated reversed phase HPLC and LC-MS/MS. In in vitro study, the production of cytokines (TNF-α, IL-1β) by lipopolysaccharide (LPS)-stimulated THP-1 macrophages were significantly reduced by P. amarus extract and its major compounds (phyllanthin, hypophyllanthin, niranthin, isolintetraline, corilagin, phyltetralin, gallic acid, geraniin and ellagic acid) in dose dependent manner. Among the active compounds, corilagin demonstrated the strongest inhibition on TNF-α release (p<0.001) with an IC50 value of 9.06 μM, while geraniin was the most potent against the release of IL-1β (p<0.001) with an IC50 value of 20.09 μM. In in vivo study, the extract dose-dependently increased body weight, bone mineral density and decreased body temperature, hind paw volume and severity of arthritis (arthritis index, % arthritis limbs, lantency time). In addition, it also significantly (P<0.001) decreased the level of serum cytokines (TNF-α, IL-1β, IL-1α, IL-6) and matrix metalloproteinase (MMP-1, MMP-3 MMP-9, TIMP-1) in the synovial fluid as well as haematological and biochemical parameters (↓WBC, ↑RBC, ↓ESR, ↓ platelet count, ↓RF factor, ↓C-reactive protein, ↓ ALT, ↓ALP, ↓AST) were also normalized as compare to arthritic group. Histopathological examination of the knee joint also revealed that the extract effectively reduced the synovitis, pannus formation, bone and cartilage destruction. In conclusion, the strong immunosuppressive effect of the plant extract on the type II collagen-induced arthritis rat model contributed by the bioactive compounds that have shown strong inhibition on the production of cytokines by LPS stimulated THP-1 macrophages. The results suggest that the standardized extract of P.amarus could be useful in the prophylaxis of RA.,Ph.D. |
| Pages: | 211 |
| Call Number: | QV247.A318a 2018 9 |
| Publisher: | UKM, Kuala Lumpur |
| Appears in Collections: | Faculty of Pharmacy / Fakulti Farmasi |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| ukmvital_103520+Source01+Source010.PDF Restricted Access | 1.88 MB | Adobe PDF |  View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.