10-Hydroxy-2-Decenoic Acid from Royal Jelly: A Potential Medicine for RAJ Ethnopharmacol, 2010 Feb 3
AIM OF THE STUDY: Rheumatoid arthritis synovial fibroblasts (RASF) are known to produce matrix metalloproteinases (MMP) and cause joint destruction. The purpose of this study is to develop a potential medicine for rheumatoid arthritis (RA).
MATERIALS AND METHODS: To this end, first, the MMPs inhibition factor was purified from an alkali-solubilized fraction of RJ (Apis mellifera) by C18 reverse-phase column chromatography and identified as 10-hydroxy-2-decenoic acid (10H2DA) by LTQ XL analysis. Next, examination was made of why 10H2DA could inhibit the activity of MMPs: With RASFs isolated from Rheumatoid tissues by enzymatic digestion, cultures in monolayers were treated with 10H2DA (0. 5, 1, 2mM) or PBS for 2h followed by stimulation with TNF-alpha (10ng/ml) for 2h, mRNA. Protein levels of MMP-1, MMP-3 were measured by real-time PCR and enzyme-linked immunosorbent assay(ELISA), the DNA binding activity of activator protein-1(AP-1) and nuclear factor kappaB (NF-kappaB) by electrophoretic mobility shift assay(EMSA), and the protein kinase activity of p38, ERK and JNK by kinase assay.
RESULTS: The molecular investigation revealed that the 10H2DA-mediated suppression was likely to occur through blocking p38 kinase and c-Jun N-terminal kinase -AP-1 signaling pathways. In contrast, 10H2DA had no effect on extracellular signal-regulated kinase activity, NF-kappaB DNA-binding activity and IkappaBalpha degradation.
CONCLUSION: These results suggest that 10H2DA may be of potential therapeutic value in inhibiting joint destruction in RA.
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