Journal of Natural Medicines

, Volume 66, Issue 2, pp 292–301 | Cite as

Pharmacological explanation for the medicinal use of Juniperus excelsa in hyperactive gastrointestinal and respiratory disorders

  • Munasib Khan
  • Arif-ullah Khan
  • Najeeb-ur-Rehman
  • Anwarul-Hassan GilaniEmail author
Original Paper


Crude extract of Juniperus excelsa (JeExt), which tested positive for the presence of anthraquinone, flavonoids, saponins, sterols, terpenes and tannin, exhibited a protective effect against castor oil-induced diarrhoea in mice at 100–1000 mg/kg. In rabbit jejunum preparations, JeExt (0.01–1.0 mg/mL) caused relaxation of spontaneous and K+ (80 mM)-induced contractions at similar concentrations to papaverine, whereas verapamil was relatively more potent against K+. JeExt (0.03–0.3 mg/mL) shifted Ca2+ concentration–response curves to the right, like papaverine or verapamil. JeExt (0.003–0.01 mg/mL) caused a leftward shift of isoprenaline-induced inhibitory concentration–response curves, similar to papaverine. JeExt (1.0–30 mg/kg) caused suppression of carbachol (CCh, 100 μg/kg)-induced increase in inspiratory pressure of anaesthetized rats. In guinea-pig trachea, JeExt (0.001–3.0 mg/mL) relaxed CCh (1 μM)- and high K+-induced contractions and shifted isoprenaline-induced inhibitory curves to the left. This study suggests that Juniperus excelsa possibly exhibits a combination of Ca2+ antagonist and phosphodiesterase inhibitory effects, which provides a pharmacological basis for its traditional use in disorders of gut and airways hyperactivity, such as diarrhoea, colic and asthma.


Juniperus excelsa Ca2+ channel blocker PDE inhibitor Gut and airways disorders 



This study was partially supported by Higher Education Commission of Pakistan. Munasib Khan was on leave from University of Malakand for the PhD study.


  1. 1.
    Shanjani PS (2003) Nitrogen effect of callus induction and plant regeneration of Juneiperus excels. Int J Agr Biol 4–5:419–422Google Scholar
  2. 2.
    Emami SA, Asili J, Mohagheghi Z, Hassanzadeh MK (2007) Antioxidant activity of leaves and fruits of Iranian conifers. Evidence Based Complem Altern Med 4:313–319CrossRefGoogle Scholar
  3. 3.
    Kaul MK (1997) Medicinal plants of Kashmir and Ladakh: temperate and cold acrid Himalaya. Indus Publishing Company, New Delhi, p 173Google Scholar
  4. 4.
    Nadkarni KM (1976) Indian materia medica, 3rd edn. Popular Prakashan, Bombay, p 713Google Scholar
  5. 5.
    Baquar SR (1989) Medicinal and poisonous plants of Pakistan. Printas, Karachi, pp 248–249Google Scholar
  6. 6.
    Usmanghani K, Saeed A, Alam MT (1997) Indusyunic medicine. University of Karachi Press, Karachi, pp 468–469Google Scholar
  7. 7.
    Thappa RK, Aggarwal SG, Kapahi BK, Sarin YK (1987) Juniperus excelsa leaf oil, a new source of cedrol. J Nat Prod 50:323–324CrossRefGoogle Scholar
  8. 8.
    Adam RP (1990) The chemical composition of leaf oils of Juniperus excelsa M. Bieb. J Essent Oil Res 2:45–48Google Scholar
  9. 9.
    Unlu M, Unlu GV, Vural N, Donmez E, Akmak O (2008) Composition and antibacterial activity of juniperus excelsa essential oil. Chem Nat Comp 44:129–131CrossRefGoogle Scholar
  10. 10.
    Muhammad I, Mossa JS, Al-Yahya MA, Ramadan AF, El-Feraly FS (2006) Further antibacterial diterpenes from the bark and leaves of Juniperus procera Hochst. ex Endl. Phytother Res 9:584–588CrossRefGoogle Scholar
  11. 11.
    Marina D, Sokovi J, Risti M, Grubi A (2004) Chemical composition and antifungal activity of the essential oil from Juniperus excelsa berries. Pharm Biol 42:328–334CrossRefGoogle Scholar
  12. 12.
    Williamson EM, Okpako DT, Evans FJ (1998) Selection preparation and pharmacological evaluation of plant material. Wiley, Chichester, pp 15–23Google Scholar
  13. 13.
    Edeoga HO, Okwu DE, Mbaebie BO (2005) Phytochemical constituents of some Nigerian medicinal plants. Afr J Biotechnol 4:685–688Google Scholar
  14. 14.
    National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington, pp 1–7Google Scholar
  15. 15.
    Khan A, Gilani AH (2011) Antidiarrheal and bronchodilatory activities of olive extract. Lat Am J Pharm 30:5–9Google Scholar
  16. 16.
    Gilani AH, Shah AJ, Ghayur MN, Majeed K (2005) Pharmacological basis for the use of turmeric in gastrointestinal and respiratory disorders. Life Sci 76:3089–3105PubMedCrossRefGoogle Scholar
  17. 17.
    Farre AJ, Columbo M, Fort M, Gutierrez B (1991) Differential effects of various Ca++ antagonists. Gen Pharmacol 22:177–181PubMedGoogle Scholar
  18. 18.
    Godfraind T, Miller R, Wibo M (1986) Calcium antagonism and calcium entry blockade. Pharmacol Rev 38:321–416PubMedGoogle Scholar
  19. 19.
    Lorenz KL, Wells JN (1983) Potentiation of the effects of sodium nitroprusside and isoproterenol by selective phosphodiesterase inhibitors. Mol Pharmacol 23:424–430PubMedGoogle Scholar
  20. 20.
    Gilani AH, Khan A, Subhan F, Khan M (2005) Antispasmodic and bronchodilator activities of St. John’s wort are putatively mediated through dual inhibition of calcium influx and phosphodiesterase. Fundam Clin Pharmacol 19:695–705PubMedCrossRefGoogle Scholar
  21. 21.
    Gilani AH, Khan A, Ali T, Ajmal S (2008) Mechanisms underlying the antispasmodic and bronchodilatory properties of Terminalia bellerica fruit. J Ethnopharmacol 116:528–538PubMedCrossRefGoogle Scholar
  22. 22.
    Shah AJ, Gilani AH (2010) Bronchodilatory effect of Acorus calamus is mediated through multiple pathways. J Ethnopharmacol 131:471–477PubMedCrossRefGoogle Scholar
  23. 23.
    Reynolds IJ, Gould RJ, Snyder SH (1984) Loperamide: blockade of calcium channels as a mechanism for antidiarrhoeal effects. J Pharmacol Exp Ther 231:628–632PubMedGoogle Scholar
  24. 24.
    Croci T, Landi M, Elmonds-Alt X, Le-Fur G, Maffrand JP, Manara L (1997) Role of tachykinins in castor oil-induced diarrhoea in rats. Br J Pharmacol 121:375–380PubMedCrossRefGoogle Scholar
  25. 25.
    Bashir S, Memon R, Gilani AH (2011) Antispasmodic and antidiarrheal activities of Valeriana hardwickii rhizome are putatively mediated through calcium channel blockade. Evidence Based Complem Altern Med 1:6Google Scholar
  26. 26.
    Rang HP, Dale MM, Ritter JM (1999) Pharmacology, 4th edn. Churchill Livingstone, New York, pp 289–290Google Scholar
  27. 27.
    Fleckenstein A (1977) Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu Rev Pharmacol Toxicol 17:149–166PubMedCrossRefGoogle Scholar
  28. 28.
    Smith BV, Spina D, Page CP (2006) Phosphodiesterase inhibitors. Br J Pharmacol 47:252–257Google Scholar
  29. 29.
    Sopory S, Kaur T, Visweswariah SS (2004) The cGMP-binding, cGMP-specific phosphodiesterase (PDE5): intestinal cell expression, regulation and role in fluid secretion. Cell Signal 16:681–692PubMedCrossRefGoogle Scholar
  30. 30.
    Evans WV, Monie RD, Crimmins J, Seton A (1980) Aminophylline, salbutamol and combined intravenous infusions in acute severe asthma. Br J Dis Chest 74:385–389PubMedCrossRefGoogle Scholar
  31. 31.
    Nielsen-Kudsk JE, Karlsson JA, Persson CGA (1986) Relaxant effects of xanthines, a β2-receptor agonist and Ca++ antagonists in guinea-pig tracheal preparations contracted by potassium or carbachol. Eur J Pharmacol 128:33–40PubMedCrossRefGoogle Scholar
  32. 32.
    Rabe KF, Magnussen H, Dent G (1995) Theophylline and selective PDE inhibitors as bronchodilators and smooth muscle relaxants. Eur Respir J 8:637–642PubMedGoogle Scholar
  33. 33.
    Murthy KS (2006) Signaling for contractions and relaxation in smooth muscle of the gut. Annu Rev Physiol 68:345–374PubMedCrossRefGoogle Scholar
  34. 34.
    Schwarz ER, Kapur V, Rodriguez J, Rastogi S, Rosanio S (2007) The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems. Int J Impot Res 19:139–148PubMedCrossRefGoogle Scholar
  35. 35.
    Lipworth BJ (2005) Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. Lancet 365:167–175PubMedCrossRefGoogle Scholar
  36. 36.
    Chung KF (2006) Phosphodiesterase inhibitors in airways disease. Eur J Pharmacol 533:110–117CrossRefGoogle Scholar
  37. 37.
    Nawarth H (1981) Action potential, membrane currents and force of contraction in cat ventricular heart muscle treated with papaverine. J Pharmacol Exp Ther 218:544–549Google Scholar
  38. 38.
    Twiss MA, Harman E, Chesrown S, Handeles L (2002) Efficacy of calcium channel blockers as maintenance therapy for asthma. Br J Clin Pharmacol 53:243–249CrossRefGoogle Scholar
  39. 39.
    Billman GE (1992) The antiarrhythmic effects of the calcium antagonists. In: Epstein M (ed) Calcium antagonists in clinical medicine. Hanley and Belfus, Philadelphia, pp 183–212Google Scholar
  40. 40.
    Gilani AH, Atta-ur-Rahman (2005) Trends in ethnopharmacology. J Ethnopharmacol 100:43–49PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer 2011

Authors and Affiliations

  • Munasib Khan
    • 1
    • 2
  • Arif-ullah Khan
    • 3
  • Najeeb-ur-Rehman
    • 1
  • Anwarul-Hassan Gilani
    • 1
    Email author
  1. 1.Natural Products Research Unit, Department of Biological and Biomedical SciencesAga Khan University Medical CollegeKarachiPakistan
  2. 2.Department of Pharmacology, Faculty of PharmacyUniversity of KarachiKarachiPakistan
  3. 3.Institute of Pharmaceutical SciencesKohat University of Science and TechnologyKohatPakistan

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