High Molecular Weight Coffee Melanoidins Are Inhibitors For Matrix Metalloproteases

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High molecular weight coffee melanoidins are inhibitors for matrix metalloproteases. - PubMed - NCBI

Abstract
High molecular (above 10 kDa) melanoidins isolated from coffee beans of varying roasting degree were found to be efficient inhibitors for the zinc-containing matrix metalloproteases MMP-1, MMP-2, and MMP-9 with IC(50) values ranging between 0.2 and 1.1 mg/mL in vitro. The inhibitory potential increased with roasting degree. No or only slight inhibition of other zinc-containing peptidases closely related to MMPs, namely, Clostridium histolyticum collagenase and angiotensin converting enzyme, was found, indicating specific structural features of melanoidins to be responsible for the interaction with MMPs. A continuous increase on the apparent molecular weight of melanoidins as well as incorporation of phenolic substances into the melanoidin structure with progress of roasting was observed, concomitant with a significant increase in the carbon/nitrogen of the melanoidins. This suggests that the melanoidins are mainly formed by incorporation of carbohydrates and phenolic compounds onto a proteinaceous backbone. As MMP-1, MMP-2, and MMP-9 play a pivotal role in pathogenesis of colorectal cancer, studies on possible physiological effects of melanoidins are mandatory.

 

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In the first part of the study it was demonstrated that high molecular melanoidins, formed
during roasting of coffee, have a specific and effective inhibitory potential against human
matrix metalloproteases (MMPs), which correlated with the roast degree of the samples.
While no inhibitory activity of the high molecular fraction obtained from green coffee beans
(mRD0), at concentrations up to 2.5 mg/mL, could be measured against the studied MMPs
1, 2 and 9, a continuous increase on the inhibitory potential of the melanoidin fraction was
observed upon roasting. For the melanoidins from the final roasted product (mRD4), IC50
values of 0.461 ± 0.006 mg/mL against MMP-1, 0.224 ± 0.040 mg/mL against MMP-2; and
0.728 ± 0.014 mg/mL against MMP-9 were measured. These results indicate a direct effect
of the roasting process on the formation of MMP-inhibiting structures within the melanoidin
complex. Noteworthy is the fact that zinc addition, in concentrations up to 50µM, did not
restore the MMP activity in the presence of melanoidins, suggesting more specific
molecular interactions between the inhibitor and the active center of the enzymes other than
single metal sequestration. Considering that a cup of coffee brew supplies 200 mg of
mRD4, the ingestion of 2 to 3 cups of coffee promotes concentrations of 0.2-0.3 mg/mL of
the non-absorbable high molecular weight melanoidins in the colonic lumen. This
concentration is in the range of the IC50 values of mRD4 against the studied MMPs,
suggesting that even conventional drinking habits can result in significant inhibition of
intestinal MMPs.

https://gut.bmj.com/content/47/1/12