Planta Med 2015; 81(02): 116-122
DOI: 10.1055/s-0034-1383391
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Antispasmodic Effects of Myrrh due to Calcium Antagonistic Effects in Inflamed Rat Small Intestinal Preparations

Cica Vissiennon
1   University of Leipzig, Institute of Pharmacy, Leipzig, Germany
,
Karl-Heinz Goos
2   REPHA GmbH Biologische Arzneimittel, Langenhagen, Germany
,
Ole Goos
2   REPHA GmbH Biologische Arzneimittel, Langenhagen, Germany
,
Karen Nieber
1   University of Leipzig, Institute of Pharmacy, Leipzig, Germany
› Author Affiliations
Further Information

Publication History

received 31 May 2014
revised 08 October 2014

accepted 06 November 2014

Publication Date:
15 January 2015 (online)

Abstract

Myrrh is the oleo-gum resin of mainly Commiphora molmol and as a powdered substance, one compound in the traditional medicinal product Myrrhinil-Intest®, which has been used for the treatment of unspecific, inflammatory intestinal disorders. The aim of the present study was to evaluate the antispasmodic effect of myrrh under healthy and inflamed conditions, and to evaluate a calcium-antagonistic effect as a possible mode of action. Therefore, an ethanolic myrrh extract was tested for its effects on muscle tone and acetylcholine-induced contractions in untreated and inflamed rat ileum/jejunum preparations. Inflammation was experimentally induced by 2,4,6-trinitrobenzene sulfonic acid (10 mM, 30 min). Additionally, the effect of the calcium channel agonist Bay K8644 in the presence of varying myrrh extract concentrations was examined. Myrrh extract (0.99 mg/mL) suppressed the acetylcholine-induced contraction down to 25.8 % in untreated and 15.2 % in inflamed preparations. Myrrh extract (0.15; 0.25 and 0.35 mg/mL) induced a concentration-dependent rightward shift of the Bay K8644 concentration-response curve in untreated and inflamed preparations with a significant EC50 shift. Schild analysis resulted in a pA2 value of 0.93 for untreated preparations. Increasing myrrh extract concentrations induced a concentration-dependent decrease of the agonistic maximum effect in untreated and inflamed preparations down to 15.8 % and 25.8 %, respectively, for the highest concentration leading to a pD2 value of 0.58. Myrrh extract reduced intestinal muscle tone and acetylcholine-induced contraction of untreated and inflamed ileum/jejunum preparations based on dual calcium antagonism characterized by a right shift of the agonistic dose-response curve and a depression of the maximum effect. The resulting reduction of intestinal motility and spasmolytic effects provide a rationale for the symptom treatment of intestinal disorders such as irritable bowel syndrome.

 
  • References

  • 1 Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine 2009; 16: 97-110
  • 2 Shen T, Li G, Wang X, Lou H. The genus Commiphora: a review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol 2012; 142: 319-330
  • 3 Claeson P, Andersson R, Samuelsson G. T-cadinol: a pharmacologically active constituent of scented myrrh: introductory pharmacological characterization and high field 1H- and 13C-NMR data. Planta Med 1991; 57: 352-356
  • 4 Claeson P, Zygmunt P, Högestätt ED. Calcium antagonistic properties of the sesquiterpene T-cadinol: a comparison with nimodipine in the isolated rat aorta. Pharmacol Toxicol 1991; 69: 173-177
  • 5 Andersson M, Bergendorff O, Shan R, Zygmunt P, Sterner O. Minor components with smooth muscle relaxing properties from scented myrrh (Commiphora guidotti). Planta Med 1997; 63: 251-254
  • 6 Camilleri M, Heading RC, Thompson WG. Clinical perspectives, mechanisms, diagnosis and management of irritable bowel syndrome. Aliment Pharmacol Ther 2002; 16: 1407-1430
  • 7 Spiller RC, Jenkins D, Thornley JP, Hebden JM, Wright T, Skinner M, Neal KR. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 2000; 47: 804-811
  • 8 Bashashati M, Rezaei N, Andrews CN, Chen C, Daryani NE, Sharkey KA, Storr MA. Cytokines and irritable bowel syndrome: where do we stand?. Cytokine 2012; 57: 201-209
  • 9 Barkhordari E, Rezaei N, Ansaripour B, Larki P, Alighardashi M, Ahmadi-Ashtiani HR, Mahmoudi M, Keramati M, Habibollahi P, Bashashati M, Ebrahimi-Daryani N, Amirzargar AA. Proinflammatory cytokine gene polymorphisms in irritable bowel syndrome. J Clin Immunol 2010; 30: 74-79
  • 10 Kanazawa M, Palsson OS, Thiwan SIM, Turner MJ, van Tilburg MAL, Gangarosa LM, Chitkara DK, Fukudo S, Drossman DA, Whitehead WE. Contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits. Am J Gastroenterol 2008; 103: 2550-2561
  • 11 Michael S, Kelber O, Hauschildt S, Spanel-Borowski K, Nieber K. Inhibition of inflammation-induced alterations in rat small intestine by the herbal preparations STW 5 and STW 6. Phytomedicine 2009; 16: 161-171
  • 12 Michael S, Abdel-Aziz H, Weiser D, Müller CE, Kelber O, Nieber K. Adenosine A2A receptor contributes to the anti-inflammatory effect of the fixed herbal combination STW 5 (Iberogast®) in rat small intestinal preparations. Naunyn Schmiedebergs Arch Pharmacol 2012; 385: 411-421
  • 13 Langhorst J, Varnhagen I, Schneider SB, Albrecht U, Rueffer A, Stange R, Michalsen A, Dobos GJ. Randomised clinical trial: a herbal preparation of myrrh, chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis – a double-blind, double-dummy study. Aliment Pharmacol Ther 2013; 38: 490-500
  • 14 Lühr K. Initialtherapie intestinaler Mykosen mit Myrrhe, Kaffeekohle und Kamillenblüten – eine Praxisstudie. EHK 1996; 45: 368-373
  • 15 Thilo-Körner DGS, Thilo-Körner G. Diagnostik und Therapie bei entzündlichen Darmerkrankungen, Divertikulose, Divertikulitis, Asthma bronchiale, Tumor-M2-PK-Erhöhungen und Kolonmetalleinlagerungen. EHK 2006; 55: 312-319 370–377
  • 16 Mercati V, Maidecchi A, Capone L. Formulation for the treatment of IBS.. Patent WO 2013/118099/A1, 2013
  • 17 Vanhoutte PM, Paoletti R. The WHO classification of calcium antagonists. Trends Pharmacol Sci 1987; 8: 4-5
  • 18 De Ponti F, Giaroni C, Cosentino M, Lecchini S, Frigo G. Calcium-channel blockers and gastrointestinal motility: basic and clinical aspects. Pharmacol Ther 1993; 60: 121-148
  • 19 Claeson P, Samuelsson G. Screening of some Somalian medicinal plants for antidiarrhoeal effects in mice. Phytother Res 1989; 3: 180-183
  • 20 Zygmunt PM, Larsson B, Sterner O, Vinge E, Högestätt ED. Calcium antagonistic properties of the sesquiterpene T-cadinol and related substances: structure-activity studies. Pharmacol Toxicol 1993; 73: 3-9
  • 21 Malykhina AP, Akbarali HI. Inflammation-induced “channelopathies” in the gastrointestinal smooth muscle. Cell Biochem Biophys 2004; 41: 319-330
  • 22 Akbarali HI, Pothoulakis C, Castagliuolo I. Altered ion channel activity in murine colonic smooth muscle myocytes in an experimental colitis model. Biochem Biophys Res Commun 2000; 275: 637-642
  • 23 Kinoshita K, Sato K, Hori M, Ozaki H, Karaki H. Decrease in activity of smooth muscle L-type Ca2+ channels and its reversal by NF-kappaB inhibitors in Crohnʼs colitis model. Am J Physiol Gastrointest Liver Physiol 2003; 285: G483-G493
  • 24 Liu X, Rusch NJ, Striessnig J, Sarna SK. Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon. Gastroenterology 2001; 120: 480-489
  • 25 Shi XZ, Sarna SK. Impairment of Ca(2+) mobilization in circular muscle cells of the inflamed colon. Am J Physiol Gastrointest Liver Physiol 2000; 278: G234-G242
  • 26 Poli E, Lazzaretti M, Grandi D, Pozzoli C, Coruzzi G. Morphological and functional alterations of the myenteric plexus in rats with TNBS-induced colitis. Neurochem Res 2001; 26: 1085-1093
  • 27 Khan I. Molecular basis of altered contractility in experimental colitis: expression of L-type calcium channel. Dig Dis Sci 1999; 44: 1525-1530