The inhibitory activity of some New Zealand honeys on selected pro-inflammatory human enzymes

Abstract

A range of New Zealand honeys was examined to determine the inhibitory effects on six proinflammatory enzymes. The honeys included Manuka, Kanuka, Rewarewa, Ling, Honeydew, Thyme, Kamahi, and Clover honeys, and collectively represent a significant proportion of the New Zealand honey crop. The enzymes examined comprised cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), myeloperoxidase (MPO), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-7 (MMP-7), and matrix metalloproteinase-9 (MMP-9). These enzymes were selected for the important pro-inflammatory roles exhibited in human tissue. In vitro inhibition assays were performed and IC50 values calculated for COX-1, COX-2, and MPO, whereas MMPs were screened and percentage inhibition reported. In general, honey types possessing elevated levels of phenolic compounds displayed greater levels of inhibition. Manuka honey was the most effective inhibitor of COX-2 (IC50 33 mg/ml), which is a pro-inflammatory mediator in tissue. Manuka honey selectively inhibited COX-2 over COX-1, in agreement with previous phenolic inhibition findings. COX-1 is a housekeeping enzyme and high levels of inhibition are not desirable. Thyme, Rewarewa, and Kanuka honeys were relatively efficient inhibitors of COX-2, and Honeydew and Ling honeys less so. However, these five honeys were less selective towards COX-2. Clover honey was neither an efficient inhibitor of COX-2 nor selective against this enzyme. Thyme and Manuka honey displayed similar inhibition of MPO with IC50 values of 1.0 and 3.5 mg/ml, respectively. This inhibition was approximately two-fold higher than Rewarewa and Kanuka honeys. The MPO inhibition was not solely due to D-fructose or the general sugar content. The level of inhibition for COX-2 and MPO was determined by the honey floral type, and correlations between marker chemicals that determine purity and inhibition could be made. Manuka honey inhibition of MMPs ranged from IC50 25 mg/ml (MMP-7) to 71 mg/ml (MMP-9) and 76 mg/ml (MMP-2). Manuka and Rewarewa honeys were the most effective inhibitors of MMP-2. The inhibition of MMP-9 was more generalised, however the indigenous darker-coloured honeys were more effective inhibitors of MMP-7. In summary, honeys harvested in New Zealand, particularly Manuka honey, appear to exhibit potentially useful inhibition of some pro-inflammatory human enzymes.