MMP-9 Anti-inflammatory Discovery

Research

The research team, led by Professor Vic Duance and Dr Emma Blain of Cardiff University, tested an extract from Boswellia frereana in an in vitro model of articular cartilage degradation using the pro-inflammatory cytokines interleukin-1 alpha and oncostatin M; the extract reduced collagen degradation and inhibited the production of several key cytokine-induced inflammatory markers, including prostaglandin E2 (PGE2) and nitric oxide (NO); more importantly, the extract significantly inhibited in the model the expression and activation of matrix metalloproteinease-9 (MMP-9). Further work has demonstrated that the active compound in the extract is epi-lupeol. More detail on this research work can be found in the article on B. frereana in the June 2010 edition of Phytotherapy Research – please click here to read the article.


Frankincense

The sap from the Boswellia tree is commonly known as frankincense in the flavour and fragrance industry and as olibanum in the pharmaceutical industry. A fundamental characteristic of the Boswellia species is the presence of boswellic acids, which are well known for their anti-inflammatory properties; however, the striking feature of B. frereana (which is native to northern Somalia) is that it contains no detectable level of boswellic acids; instead 60% of the resin comprises epi-lupeol.

The patent application

The reference of the patent application is PCT/GB/2010/001286 [WO2011/010080], now pending in Europe, USA and China; please click here to read.

There is a great deal of prior art on the anti inflammatory properties of lupeol, of which epi-lupeol is an isomer. However, tests have been carried out which show that epi-lupeol is far more effective than lupeol in inhibiting the expression of MMP-9. Using a cell-free MMP-9 colorimetric drug discovery ELISA, epi-lupeol was observed to have between 4 and 7 – fold greater efficacy than lupeol in inhibiting MMP-9 (fold changes dependent on epi-lupeol/lupeol concentrations). Increased MMP-9 inhibition by epi-lupeol, compared with lupeol, was also confirmed in the in vitro inflammatory model of articular cartilage degradation.

Applications

The initial research work was confined to arthritis models. However, given that inflammation is implicated in a wide variety of diseases and that epi-lupeol is effective at inhibiting MMP-9, further work has been, and is being, done on other applications. To give just one example, in animal trials involving a murine model of acute Sodium Dextran Sulphate – induced colitis, it was found that the shortening of the colon was reduced by 27% for mice treated with an extract from B. frereana when compared with a saline treated group.

Enquiries

Should you have any technical enquiries please contact our research Director Dr Ahmed Ali by email alia@cardiff.ac.uk. For all other queries (including outlicensing possibilities) please contact acoyle@comptongroup.com