The Effect of Thyme Extract on β₂-Receptors and Mucociliary Clearance

Abstract

Thyme is a broncholytic und secretomotoric agent. Thus, our aim was to investigate the influence of a thyme extract on β₂-receptors in competition binding experiments and relaxation experiments on rat uteri and trachea. Furthermore, the influence of the extract on respiratory clearance was of interest. Binding experiments were performed using purified rat lung membranes with the β₂-receptor ligand [¹²⁵I]-CYP {[¹²⁵I]-(±)-Iodocyanopindolol}. The transport of the fluorescence dye rhodamin 123 concerning ciliary action in the tracheal area of a mouse was investigated using a microdialysis technique. The thyme extract reduces only slightly [¹²⁵I]-CYP binding and amplifies the displacement of [¹²⁵I]-CYP by propranolol (non-specific β-receptor antagonist): the displacement curve in the concentration range representing β₂-receptors (nM) is shifted to the left. Thyme extract had relaxing effects on organs possessing β₂-receptors (uterus and trachea). The propranolol-induced antagonism to isoprenaline is reverted concentration-dependently by the extract. A duplication of the rate of ciliary clearance by the extract was observed. In conclusion: 1) There is evidence for an influence of a thyme extract on β₂-receptors by both binding studies and biological effects: As can be derived from the shift of the propranolol displacement curve (nM), ingredients of the thyme extract slightly interact with β₂-receptors in rat lung tissue. This effect is indirect since no full range competition curve was reached. 2) An at least indirect interaction with β₂-receptors in rat uteri and trachea is revealed by a decreased antagonism of propranolol on the relaxing effect of isoprenaline by the plant extract. 3) An additional mechanism is presumed because at high extract concentrations isoprenaline-induced relaxation is complete, whereas the displacement of propranolol at β₂-receptors is only weak. 4) Thyme extract has an indirect (modulatory) effect on the β₂-receptor system. 5) Mucociliary clearance is improved in vivo. Its mechanism has still to be elucidated.

Thymus vulgaris - Lamiaceae - thyme extract - β₂-receptors - mucociliary clearance - trachea

References

• 1 Meister A, Bernhardt G, Christoffel V, Buschauer A. Antispasmodic activity of Thymus vulgaris extract on the isolated guinea-pig trachea: discrimination between drug and ethanol effects.  Planta Med. 1999;  65 512-6.
• 2 Jensen B, Dyrud O K. The smooth muscle relaxing effect of thyme (Thymus vulgaris L.)  Acta Pharmacol Toxicol. 1962;  19 345-55.
• 3 N.N. Kommission E. Cologne: Bundesanzeiger Verlagsgesellschaft; 1984, 1992, 1990: 228, 226, 250. Available online at www.bfarm.de. 
• 4 Van Den Broucke C O, Lemli J L. Antispasmodic activity of Origanum compactum. Part 2: Antagonistic effect of thymol and carvacrol.  Planta Med. 1982;  45 88-90.
• 5 Van Den Broucke C O, Lemli J L. Pharmacological and chemical investigation of thyme liquid extracts.  Planta Med. 1981;  41 129-35.
• 6 Van Den Broucke C O, Lemli J L. Spasmolytic activity of the flavonoids from Thymus vulgaris .  Pharm Weekbl Sci. 1983;  5 9-14.
• 7 Van Den Broucke C O, Lemli J L. Antispasmodic activity of Origanum compactum .  Planta Med. 1980;  38 317-31.
• 8 Astudillo A, Hong E, Bye R, Navarrete A. Antispasmodic activity of extract and compounds of Acalypha phleodies Cav.  Phytother Res. 2004;  18 102-6.
• 9 Marti D, Villagrasa V, Martinez-Solis I, Blanquer A, Castillo E, Royo L M. Histological and pahrmacological study of Thymus piperella .  Phytother Res. 2005;  19 298-302.
• 10 Grubb B R, Jones J H, Boucher R C. Mucociliary transport determined by in vivo microdialysis in the airways of normal and CF mice.  Am J Physiol Lung Cell Mol Physiol. 2004;  286 L588-95.
• 11 Lemoine H, Overlack C. Highly potent beta-2 sympathomimetics convert to less potent partial agonists as relaxants of guinea pig tracheae maximally contracted by carbachol. Comparison of relaxation with receptor binding and adenylate cyclase stimulation.  J Pharmacol Exp Ther. 1992;  261 258-70.
• 12 Lemoine H, Overlack C, Kohl A, Worth H, Reinhardt D. Formoterol, fenoterol, and salbutamol as partial agonists for relaxation of maximally contracted guinea pig tracheae: comparison of relaxation with receptor binding.  Lung. 1992;  170 63-80.
• 13 Lemoine H, Worth H, Reinhardt D. Pharmacologic characterization of formoterol in comparison with isoprenaline, fenoterol and salbutamol in tracheal muscle strips and lung membranes of the guinea pig.  Pneumologie. 1993;  47 303-10.
• 14 Akcasu A. The actions of drugs on the isolated trachea.  J Pharm Pharmacol. 1952;  4 671.
• 15 Constantine J. The spirally cut tracheal strip preparation.  . 1965;  17 384-5.
• 16 Emmerson J, Mackay D. The zig-zag tracheal strip.  J Pharm Pharmacol. 1979;  31 798.
• 17 Szarek J, Spurlock B. Antagonism of cholinergic nerve-mediated contractions by the sensory nerve inhibitory system in rat bronchi.  J Appl Physiol. 1996;  81 260-5.
• 18 Vaughan C W, Christie M J. Increase by the ORL1 receptor (opioid receptor-like1) ligand, nociceptin, of inwardly rectifying K conductance in dorsal raphe nucleus neurones.  Br J Pharmacol. 1996;  117 1609-11.
• 19 Helyes Z, Nemeth J, Pinter E, Szolsanyi J. Inhibition by nociceptin of neurogenic inflammation and the release of SP and CGRP from sensory nerve terminals.  Br J Pharmacol. 1997;  121 613-5.
• 20 Peiser C, Undem B J, Fischer A. Nociceptin effects in the airways.  Peptides. 2000;  21 995-8.