Syce, J.A.Harris, Lynne2022-10-102024-05-152022-10-102024-05-152002https://hdl.handle.net/10566/15124Magister Pharmaceuticae - MPharmThe overall objective of this study was to investigate the claims that Mentha longifolia (ML) and Artemisia afra (AA) have anti-asthmatic properties. To realize this objective we were to determine the effects that the plants may have on contractions induced by agonists (e.g. methacholine, histamine, and leukotriene D+) and also to partially investigate the mechanism that may be involved' We hypothesized that extracts of Mentha longifolia and Artemisia afra would have respiratory airway smooth muscle relaxant properties and would be able to reverse methacholine and/or, histamine and/or leukotriene D+-induced contractions. plants were collected from Kirstenbosch National Botanical Institute and aqueous extracts prepared. Solutions of plant extracts were injected into an organ bath containing a zigzag cut guinea pig tracheal strip that had been pre-contracted with methacholine, histamine or leukotriene D+. The relaxant effects of the plants were expressed as a percentage of the maximal effect produced by isoprenaline (6.67}.10'sM). To determine the mechanism for the muscle relaxant effects of the plants, cumulative log dose-response curves (LDRC) for methacholine and histamine were obtained in the absence and presence of 2%o, l0%o and 20%o solutions of the plant extracts. In addition the possible involvement of a P2- adrenoreceptor-mediated mechanism was assessed by determining the effects of increasing concentrations of ML and AA on methacholine-induced contractions in the absence and the presence of propranolol. ML produced no direct contractile effect on the guinea pig tracheal muscle, but it relaxed methacholine (6.67X10-8M1-induced contractions in a dose dependent manner. ML was able to fully reverse the methacholine-induced contraction but the 2% and 10% solutions caused a non-parallel rightward shift in the LDR curves. In concentrations above 0.1% ML gave a lO0% relaxation of histamine-induced (6.67X104M) contractions. However, except for a slight leftward shift induced by 2yo ML, the plant extract had no significant effect on the histamine LDRC' Concentrations of ML > 5 o/o produced maximal relaxation of LTD+-induced (6.93X104M) contraction. Finally, in the presence of propranolol (6.67X10{M) the maximal relaxant effect of ML on methacholine (6.67x10'sM)-induced contractions was reduced by approximately 20%. AA produced no direct contractile effect on the guinea pig tracheal muscle, but on tracheal tissue not previously exposed to methacholine it produced a dose dependent relaxation. When the tissue had, however, been exposed to methacholine and thoroughly washed before being exposed to doses of plant extract, 1%o and 2 % AA solutions induced major contractile responses and displaced the LDRC upwards, while l0%o to 30% AA solutions induced relaxation. These contractile responses were inhibited by ipratropium (1.67X10rM) and mepyramine (4.13X104M). In the presence of 20% AA there was a pronounced non-parallel rightward shift of the LDRC of methacholine. AA, 10% to 30%o, also caused a dose-dependent relaxation of histamine (6.67X10{M)- and LTD+ (6.93x10'eM)-induced contractions. Finally, in the presence of propranolol (6.67X104M) the maximal relaxant effect of AA on methacholine (6.67X105IOinduced contractions was reduced by approximately 27%. Collectively these results indicate that aqueous extracts of Mentha longifolia and Artemisia afra have potent and qualitatively similar smooth muscle relaxant activity. These actions may be mediated via several receptor pathways and/or involve one or more common intermediate step (e.g. intracellular calcium flux) commonly involved in the mechanism of action of the agonists used. The results also very strongly suggest that the extracts may contain more than one active principle some of which may differ between the two plants. Overall the results confirm that aqueous solutions of Mentha longifolia and Artemisia afra, as used in local traditional practice, have potent bronchodilator activity that could be useful in the treatment of asthma.enMentha longifolia (ML)Artemisia afra (AAKirstenbosch National Botanical Institute (KNBI)Log Dose-Response Curves (LDRC)MethacholineIsoprenalineIpratropiumGlucocorticoidsUniversity of the Western Cape