Human monoamine oxidase enzyme inhibition by coffee and β-carbolines norharman and harman isolated from coffee

Evaluation of the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to toxic pyridinium cations by monoamine oxidase (MAO) enzymes and its use to search for new MAO inhibitors and protective agents

“…In addition, the naturallyoccurring β-carboline norharman that was isolated from tobacco smoke as previously 34 , highly reduced the formation of pyridinium species by MAO-B ( Figure 9B). Similar results were obtained using norharman isolated from coffee extracts 35 ( Figure 9C). On the other hand, harman isolated from tobacco smoke or coffee inhibited MAO-A (harman at 1.5 μM into the assay reduced the formation of MPDP + + MPP + by about 36%).…”

“…Results regarding inhibition of β-carbolines, deprenyl or clorgyline were comparable to those obtained by using kynuramine or other substrates of MAO 1,30,34,35,40 . The procedure employed has the advantage of using human MAO isozymes with a true neurotoxin as substrate (i.e.…”

“…Thus, the reduction of pyridinium species produced by MAO-B in presence of R-deprenyl, a known neuroprotectant used in PD therapy, showed the suitability of this approach ( Figure 6). Also, norharman, a naturallyoccurring β-carboline alkaloid, reported to be a competitive inhibitor of MAO-B and possible neuroprotectant analog 34,35,39,40 , inhibited and decreased the oxidation of MPTP to neurotoxic species (MPDP + and MPP + ) ( Figure 6) with an IC 50 of 2.9 ± 0.1 μM and a K i of 0.85 μM calculated for competitive inhibition 41 . In the same assay, harman (1-methyl-β-carboline) did not show significant inhibition up to 20 μM, indicating that this β-carboline is a poor inhibitor of MAO-B.…”

“…HPLC grade acetonitrile, methanol and dimethyl sulfoxide (DMSO) were from Scharlau (Spain) and dichloromethane from Merck. Cigarrette and coffee extracts, as well as the isolation of β-carbolines from those samples were obtained as above 34,35 and used for inhibition studies of the oxidation of MPTP to neurotoxicant pyridinium species.…”

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

“…Subsequent studies, however, clearly demonstrated that reduced MAO activity was rather caused by smoking per se rather than being a type of biomarker or predisposition for the disease (Berlin, Spreux-Varoquaux, Saïd, & Launay, 1997;Simpson et al, 1999). In-vitro studies confirmed that harman and norhaman alkaloids found in tobacco smoke inhibit MAO-A and both MAO-A/MAO-B, respectively (Herraiz & Chaparro, 2005).…”