Planta Med 2010; 76(4): 311-318
DOI: 10.1055/s-0029-1186179
Pharmacology
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Impact of Thymol in Thyme Extracts on Their Antispasmodic Action and Ciliary Clearance

Frank Begrow1 , Jonas Engelbertz1 , Björn Feistel2 , Romanus Lehnfeld3 , Katrin Bauer1 , Eugen J. Verspohl1
  • 1Department of Pharmacology, Institute of Medicinal Chemistry, Münster, Germany
  • 2Finzelberg GmbH & Co. KG, Andernach, Germany
  • 3Phytolab GmbH & Co. KG, Vestenbergsgreuth, Germany
Weitere Informationen

Publikationsverlauf

received April 23, 2009 revised August 27, 2009

accepted Sept. 2, 2009

Publikationsdatum:
06. Oktober 2009 (online)

Abstract

Thyme is a herb with broncholytic und secretomotoric effects. Its activity on β2 receptors as a possible mechanism of action was demonstrated. Major components are thymol and carvacrol which are claimed to be responsible for its effects and, therefore, used for standardization in the German pharmacopoeia (0.03 % phenols calculated as thymol). Our aim was to investigate the impact of thymol by using thyme extracts with either normal or extremely low thymol concentrations (< 0.005 % or > 0.038 %). The antispasmodic effect on smooth muscles of the trachea and the ileum and the effect on ciliary activity (respiratory clearance) were investigated. In addition, pure thymol and carvacrol were investigated separately and in spiking experiments. Thymol and carvacrol had a concentration-dependent antispasmodic effect in the rat trachea either being stimulated by acetylcholine, K+ or Ba++. The same result was observed with respect to the increase of mucociliary transport in mice. Extracts with very low thymol contents are effective in all models used except acetylcholine-induced rat ileum contraction. When thyme extracts with normal thymol contents or with very low thymol contents were compared, the extract with normal thymol contents was more effective, both as a relaxant (rat ileum) and as an antispasmodic compound (rat trachea contraction induced by either acetylcholine, Ba++ or K+) and in ciliary transport experiments. Thyme extracts with very low thymol contents (practically free of volatile oil) were equally effective with respect to endothelin effects. When an extract with very low thymol contents is spiked with increasing concentrations of thymol, a concentration-dependent increase concerning the antispasmodic effect (Ba++-induced trachea contraction) is observed. In conclusion, the data show that in various models of antispasmodic effect (ileum and trachea) and by measuring ciliary activity, thymol (and carvacrol) is (are) active, although other not identified components of thyme extract appear to be very important as well, since extracts with very low thymol contents are active. On the basis of these results the standardization on thymol alone appears not to be justified.

References

  • 1 Marti D, Villagrasa V, Martinez-Solis I, Blanquer A, Castillo E, Royo L M. Histological and pharmacological study of Thymus piperella.  Phytother Res. 2005;  19 298-302
  • 2 Adzet T M V. Luteolin and 6-hydroxyluteolin: taxonomically important flavones in the genus Thymus.  Planta Med. 1980;  46 52-55
  • 3 Adzet T, Vila R, Canigueral S. Chromatographic analysis of polyphenols of some Iberian Thymus.  J Ethnopharmacol. 1988;  24 147-154
  • 4 Loziene K, Vaiciuniene J, Venskutonis P R. Chemical composition of the essential oil of creeping thyme (Thymus serpyllum s.l.) growing wild in Lithuania.  Planta Med. 1998;  64 772-773
  • 5 Stahl-Biskup E. The essential oil from Norwegian Thymus species. I. Thymus praecox ssp. arcticus.  Planta Med. 1986;  52 36-38
  • 6 Stahl-Biskup E. The essential oil from Norwegian Thymus species; II. Thymus pulegioides.  Planta Med. 1986;  52 233-235
  • 7 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;  65 512-516
  • 8 Jensen K B, Dyrud O K. The smooth muscle relaxing effect of thyme (Thymus vulgaris L.).  Acta Pharmacol Toxicol. 1962;  19 345-355
  • 9 Wienkötter N, Begrow F, Kinzinger U, Schierstedt D, Verspohl E J. The effect of thyme extract on beta2-receptors and mucociliary clearance.  Planta Med. 2007;  73 629-635
  • 10 Kommission E of BfArM, Germany. 
  • 11 Van Den Broucke C O, Lemli J L. Antispasmodic activity of Origanum compactum. Part 2: antagonistic effect of thymol and carvacrol.  Planta Med. 1982;  45 188-190
  • 12 Astudillo A, Hong E, Bye R, Navarrete A. Antispasmodic activity of extract and compounds of Acalypha phleodies Cav.  Phytother Res. 2004;  18 102-106
  • 13 Beer A M, Lukanov J, Sagorchev P. Effect of thymol on the spontaneous contractile activity of the smooth muscles.  Phytomedicine. 2007;  14 65-69
  • 14 Haeseler G, Maue D, Grosskreutz J, Bufler J, Nentwig B, Piepenbrock S, Dengler R, Leuwert M. Voltage-dependent block of neuronal and skeletal muscle sodium channels by thymol and menthol.  Eur J Aneasthesiol. 2002;  19 571-579
  • 15 Lee S P, Buber M T, Yang Q, Cerne R, Cortés R Y, Sprous D G, Bryant R W. Thymol and related alkyl phenols activate the hTRPA1 channel.  Br J Pharmacol. 2008;  153 1-11
  • 16 Braun T, Voland P, Kunz L, Prinz C, Gatzl M. Enterochromaffin cells of the human gut: sensors for spices and odorants.  Gastroenterology. 2007;  132 1890-1901
  • 17 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-L595
  • 18 Van Den Broucke C O, Lemli J L. Spasmolytic activity of the flavonoids from Thymus vulgaris.  Pharm Weekbl Sci. 1983;  5 9-14
  • 19 Van Den Broucke C O, Lemli J L. Pharmacological and chemical investigation of thyme liquid extracts.  Planta Med. 1981;  41 129-135
  • 20 Engelbertz J, Schwenk T, Kinzinger U, Schierstedt D, Verspohl E J. Thyme extract, but not thymol, inhibits endothelin-induced contractions of isolated rat trachea.  Planta Med. 2008;  74 1-5

Dr. E. J. Verspohl

Institute of Medicinal Chemistry
Department of Pharmacology
Westfälische Wilhelms-University of Münster

Hittorfstraße 58–62

48149 Münster

Germany

Telefon: + 49 25 18 33 33 39

Fax: + 49 25 18 33 21 44

eMail: verspoh@uni-muenster.de