Swertiamarin ameliorates inflammation and osteoclastogenesis intermediates in IL-1β induced rat fibroblast-like synoviocytes.
OBJECTIVE
Rheumatoid arthritis is a chronic inflammatory and autoimmune disease that leads to aggressive joint cartilage and bone destruction. Swertiamarin is a secoiridoid glycoside found in Enicostema axillare (Lam) A. Raynal, a medicinal plant used in the Indian system of traditional medicine. In the present study, the potential of swertiamarin was evaluated in IL-1β induced fibroblast-like synoviocytes (FLS).


METHODS
The FLS were isolated from Freund's Complete Adjuvant induced arthritic (AA) rats and cultured with IL-1β. The normal FLS and AA-FLS were cultured and used for subsequent experiment in fibroblastic morphology form. The efficacy of swertiamarin (10-50 μg/ml) was evaluated on mRNA and protein expression levels of inflammatory and osteoclastogenesis mediators. The efficacy was also evaluated on p38 MAPKα levels with time course studies (2, 4, 6, 8 and 12 h).


RESULTS
IL-1β induced cell proliferation (149.46 ± 13.73 %) and NO production (162.03 ± 11.03%) in AA-FLS; treatment with swertiamarin controlled proliferation (82.77 ± 4.22%) and NO production (82.06 ± 3.91% at 50 μg/ml) in a dose-dependent manner. It also significantly (P < 0.05) modulated the expression of apoptotic marker (caspase 3), proinflammation mediators (TNFα, IL-6, PGE2, COX-2, iNOS, MMPs) and osteoclastogenic mediator (RANKL) at both the mRNA and protein levels. Treatment with swertiamarin inhibited the levels of p38 MAPKα in a dose-dependent manner and also significantly (P < 0.05) attenuated the release of the same in time dependent mode.


CONCLUSIONS
These findings suggest that treatment with swertiamarin attenuated IL-1β induced FLS, and it revealed anti-inflammatory potential by attenuating aggressive FLS.
Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, 600 034, Tamil Nadu, India.
S
S
Saravanan
V I Hairul
VI
Islam
K
K
Thirugnanasambantham
N
N
Pazhanivel
N
N
Raghuraman
M Gabriel
MG
Paulraj
S
S
Ignacimuthu
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D057888:Iridoid Glucosides / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000276:immunology; D010010:Osteoclasts / Q000166:cytology; D011753:Pyrones / Q000494:pharmacology*; D053245:RANK Ligand / Q000276:immunology; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D057888:Iridoid Glucosides; D011753:Pyrones; D053245:RANK Ligand; D009569:Nitric Oxide; C013270:swertiamarin; D048051:p38 Mitogen-Activated Protein Kinases