2',3,5,7-Tetrahydroxyflavone
2',3,5,7-Tetrahydroxyflavone inhibits MMP-13 expression in IL-1β-treated chondrocytes, at least in part, by suppressing the c-Fos/AP-1 and JAK2/STAT1/2 pathways.
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Journal of Pharmacological Sciences, 21 May 2011, 116(2):221-231.
Effects of flavonoids on matrix metalloproteinase-13 expression of interleukin-1β-treated articular chondrocytes and their cellular mechanisms: inhibition of c-Fos/AP-1 and JAK/STAT signaling pathways.[Reference:
WebLink]
To identify the therapeutic potential for cartilage degradation and its action mechanisms, the effects of naturally-occurring flavonoids on matrix metalloproteinase-13 (MMP-13) induction were examined in the human chondrocyte cell line SW1353.
METHODS AND RESULTS:
Flavones including apigenin and wogonin strongly inhibited MMP-13 induction in interleukin (IL)-1β-treated SW1353 cells, while flavonols such as kaempferol, quercetin, and flavanone (naringenin) did not at 5 - 25 µM. Apigenin and wogonin primarily inhibit MMP-13 by blocking the c-Fos / activator protein-1 (AP-1) and Janus kinase 2 (JAK2) / signal transducer and activator of transcription 1/2 (STAT1/2) pathways, but not nuclear factor-κB (NF-κB) signaling. Apigenin was also shown to inhibit extracellular matrix degradation in rabbit cartilage culture. The following study using some synthetic flavones demonstrated that A-ring C-5,7-dihydroxyl and B-ring dihydroxyl substitution at C-2,3, C-2,4, or C-3,4 are important for the suppression of MMP-13 expression. Among these flavones,
2',3,5,7-Tetrahydroxyflavone also inhibited both the c-Fos/AP-1 and STAT1/2 pathways.
CONCLUSIONS:
Taken together, these results indicate that certain flavonoids, especially flavones, inhibit MMP-13 expression in IL-1β-treated chondrocytes, at least in part, by suppressing the c-Fos/AP-1 and JAK2/STAT1/2 pathways. Furthermore, these findings suggest that some flavonoids have the potential for protecting against collagen matrix breakdown in the cartilage of diseased tissues such as those found in arthritic disorders.
