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9,10‐Dihydro‐2,5‐dimethoxyphenanthrene‐1,7‐diol, from Eulophia ochreata , inhibits inflammatory signalling mediated by Toll‐like receptors
Author(s) -
Datla Praneel,
Kalluri Mani Deepthi,
Basha Khalander,
Bellary Akshaya,
Kshirsagar Rajendra,
Kanekar Yogesh,
Upadhyay Shakti,
Singh Shiva,
Rajagopal Vikram
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.00780.x
Subject(s) - biology , tlr4 , lipopolysaccharide , cytokine , receptor , tumor necrosis factor alpha , pharmacology , inflammation , biochemistry , immunology
Background and purpose: 9,10‐Dihydro‐2,5‐dimethoxyphenanthrene‐1,7‐diol (RSCL‐0520) is a phenanthrene isolated from Eulophia ochreata , one of the Orchidaceae family, known by local tradition to exhibit medicinal properties. However, no anti‐inflammatory activity or any molecular mechanisms involved have been reported or elucidated. Here, for the first time, we evaluate the anti‐inflammatory properties of RSCL‐0520 on responses induced by lipopolysaccharide (LPS) and mediated via Toll‐like receptors (TLRs). Experimental approach: The in vitro anti‐inflammatory activities of RSCL‐0520 were investigated in LPS‐stimulated monocytic cells, measuring activation of cytokine and inflammatory genes regulated by nuclear factor‐κB (NF‐κB). Tumour necrosis factor (TNF)‐α levels in serum following LPS stimulation in mice and carrageenan‐induced paw oedema in rats were used as in vivo models. Key results: Pretreatment with RSCL‐0520 effectively inhibited LPS‐induced, TLR4‐mediated, NF‐κB‐activated inflammatory genes in vitro , and reduced both LPS‐induced TNF‐α release and carrageenan‐induced paw oedema in rats. Treatment with RSCL‐0520 reduced LPS‐stimulated mRNA expression of TNF‐α, COX‐2, intercellular adhesion molecule‐1, interleukin (IL)‐8 and IL‐1β, all regulated through NF‐κB activation. RSCL‐0520, however, did not interfere with any cellular processes in the absence of LPS. Conclusions and implications: RSCL‐0520 blocked signals generated by TLR4 activation, as shown by down‐regulation of NF‐κB‐regulated inflammatory cytokines. The inhibitory effect involved both MyD88‐dependent and ‐independent signalling cascades. Our data elucidated the molecular mechanisms involved, and support the search for plant‐derived TLR antagonists, as potential anti inflammatory agents.