10-Hydroxy-2-decenoic acid from Royal jelly: a potential medicine for RA.
OBJECTIVE
Rheumatoid arthritis synovial fibroblasts (RASFs) are known to produce matrix metalloproteinases (MMPs) and cause joint destruction. The purpose of this study is to develop a potential medicine for rheumatoid arthritis (RA).


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, Experimental test 10H2DA how to inhibited the activities of MMPs: with RASFs isolated from rheumatoid tissues by enzymatic digestion, cultures in monolayers were treated with 10H2DA (0.5mM, 1mM, and 2mM) or PBS for 2h followed by stimulation with TNF-alpha (10 ng/ml) for 2h, mRNA. Protein levels of MMP-1 and 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.


CONCLUSIONS
These results suggest that 10H2DA may be of potential therapeutic value in inhibiting joint destruction in RA.
Department of Medicinal Chemistry, Pharmacy School, Wenzhou Medical College, Wenzhou, China.
Xin-Yu
XY
Yang
De-sheng
DS
Yang
Wei-Zhang
Jian-Min
JM
Wang
Chun-Yang
CY
Li
Hui-Ye
Kang-Fu
KF
Lei
Xiu-Fang
XF
Chen
Nian-Han
NH
Shen
Li-Qin
LQ
Jin
Jian-Guang
JG
Wang
D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005227:Fatty Acids / Q000737:chemistry*; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000099219:Royal Jelly
D018501:Antirheumatic Agents; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D048031:JNK Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3; D020782:Matrix Metalloproteinases; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D000099219:Royal Jelly; C052476:2-decenoic acid; C055543:10-hydroxy-2-decenoic acid