Studies on the interactions of tobacco leaf and tobacco smoke constituents and monoamine oxidase.
Studies have demonstrated that smokers have lower levels of brain monoamine oxidase (MAO) A and B activity and lower MAO-B platelet activity than non-smokers. Recent speculations suggest that in addition to nicotine, tobacco components which are MAO inhibitors, may contribute to some tobacco related psychopharmacological effects. Furthermore, epidemiological evidence indicates a lower incidence of Parkinson's disease in smokers than in non-smokers. This relationship also might be linked to MAO inhibition. These intriguing observations prompted studies on the effects of tobacco leaf and tobacco smoke constituents on MAO activity. Studies reported here demonstrate that crude hexane tobacco leaf and hexane and aqueous leaf extracts have MAO inhibitory properties. Rat brain mitochondrial MAO-A and MAO-B activity are not altered following continuous 28 day exposure to (osmotic minipump) to two tobacco alkaloids, (S)-nicotine or (R,S)-N-methylanatabine. However, earlier studies in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated parkinsonian C57BL/6 mouse model have provided indirect evidence that the tobacco derived 2,3,6-trimethyl-1,4-naphthoquinone (an MAO-A and B inhibitor) is effective in inhibiting MAO-B in vivo and is neuroprotective. Results reported here from more extensive tobacco leaf extractions provide evidence for three additional compounds with MAO-B inhibitory properties. One contains a chromone system, another a polyunsaturated macro-cycle and the third we have identified as farnesylacetone. These findings provide support to the thesis that components of tobacco smoke may be responsible for the inhibition of brain MAO-A and brain and platelet MAO-B in human smokers.
Castagnoli
Kay
K
Harvey W. Peters Center, Department of Chemistry, Virginia Tech., Blacksburg, VA 24061-0212, USA. kcastagn@vt.edu
Steyn
Stefanus J
SJ
Magnin
Geraldine
G
Van Der Schyf
Cornelis J
CJ
Fourie
Izel
I
Khalil
Ashraf
A
Castagnoli
Neal
N