Background Boswellia serrata gum resin has attracted pharmacological interest as an alternative antinflammatory. Purpose We studied the application of an ethanolic extract of the resin and its main active 3-O-acetyl-11-keto-Î²-boswellic acid (AKBA) against inflammatory degeneration of skin extracellular matrix. Study design We compared the effects of the extract and AKBA on the activity of MMP-2 and MMP-9 (72-kDa and 92-kDa type IV collagenases) in HaCaT keratinocytes exposed to interleukin-1Î± (IL-1Î±) as a skin inflammation model. Methods MMP activity in cell conditioned medium was assayed by gelatin zymography, while NF-KB and MAP kinase activations were evaluated by Western blotting. Results IL-1Î± (10 ng/ml) upregulated MMP-9 but not MMP-2 in HaCaT cells. The extract, used at 2.3, 4.6 and 9.3 Âµg/ml, had no effect, but in combination with IL-1Î± showed MMP-9 inhibition at the lowest dose and increased upregulation at the highest one. AKBA alone, at the same concentrations (corresponding to 5, 10, and 20 ÂµM), did not stimulate MMP-9, but together with IL-1Î± induced an increased upregulation at the lowest dose that progressively disappeared at higher doses. WB analysis showed that IL-1Î± induced phosphorylation of NF-ÎºB p65, while AKBA abolished this effect at 20 ÂµM, but conversely increased it at 5 ÂµM. Screening of MAP kinase phosphorylation showed a combined activation of IL-1Î±/AKBA on JNK, while the JNK inhibitor SP600125 abolished MMP-9 upregulation induced by IL-1Î±/AKBA. Conclusion The enhancing effect of IL-1Î±/AKBA on MMP-9 at low AKBA concentration seems to involve the activation of JNK-mediated NF-ÎºB pathway. Conversely, the extract inhibits the IL-1Î± effect at low doses, but not at higher ones, where AKBA and possibly other Î²-boswellic acids reach concentrations that potentiate the effect of IL-1Î±. The extract at low doses could protect the skin against degenerative processes of extracellular matrix, while keto-Î²-boswellic acids seem unsuitable for this purpose.
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|Titolo:||The major Boswellia serrata active 3-acetyl-11-keto-Î²-boswellic acid strengthens interleukin-1Î± upregulation of matrix metalloproteinase-9 via JNK MAP kinase activation|
|Data di pubblicazione:||2017|
|Appare nelle tipologie:||01.01 - Articolo su rivista|