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Swertiamarin, a natural steroid, prevent bone erosion by modulating RANKL/RANK/OPG signaling.

Abstract：

:Bone erosion is a central feature of rheumatoid arthritis (RA) that is characterized by the infiltration of the synovial lining by osteoclasts and lymphocytes. In the present study, swertiamarin a major secoiridoid glycoside was evaluated for anti-osteoclastogenic property to prevent bone erosion in Freund's complete adjuvant (FCA) induced in-vivo model, in-vitro osteoblast and osteoclasts as well as in co-culture system and in-silico molecular docking analysis. The swertiamarin treatment decreased the expression of TRAP, RANKL, and RANK levels and increased the levels of OPG levels significantly in both in vitro and in vivo models. In in vitro, the compound treatment significantly increased the cell proliferation and ALP levels in osteoblast cells; the high proliferation (153.8600±5.23%) and ALP release (165.6033±4.13%) were observed at 50μg/ml concentration of swertiamarin treatment. At the same time the treatment decreased the TRAP positive cells in osteoclast cells; the high reductions of TRAP positive cells (39.32±3.19%) were observed at 50μg/ml of swertiamarin treatment. The treatment modulated the levels of pro-inflammatory cytokines, MMPs and NF-κB levels in osteoblast and osteoclast co-culture system. In in silico analysis swertiamarin had affinity towards the proteins RANK, RANKL and OPG residues with low binding energy -4.5, -3.92 and -5.77kcal/mol respectively. Thus, the results of this study revealed the anti-osteoclastogenic activity of swertiamarin on the prevention of bone destruction.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Hairul-Islam MI,Saravanan S,Thirugnanasambantham K,Chellappandian M,Simon Durai Raj C,Karikalan K,Gabriel Paulraj M,Ignacimuthu S

doi

10.1016/j.intimp.2017.10.022

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

114-124

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(17)30402-2

journal_volume

53

pub_type

杂志文章

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