Planta Med 2005; 71(2): 120-125
DOI: 10.1055/s-2005-837777
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Presence of Antispasmodic, Antidiarrheal, Antisecretory, Calcium Antagonist and Acetylcholinesterase Inhibitory Steroidal Alkaloids in Sarcococca saligna

Anwar-ul Hassan Gilani1 , Mohammad Nabeel Ghayur1 , Asaad Khalid2 ,  Zaheer-ul-Haq2 , Muhammad Iqbal Choudhary2 ,  Atta-ur-Rahman2
  • 1Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi, Pakistan
  • 2Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical Sciences, University of Karachi, Karachi, Pakistan
Further Information

Publication History

Received: May 17, 2004

Accepted: August 29, 2004

Publication Date:
24 February 2005 (online)

Abstract

The aim of this investigation was to see if the crude extract of Sarcococca saligna (Ss.Cr) contains chemicals with gut function inhibitory activity by using in vitro and in vivo assays. Ss.Cr caused a dose-dependent (0.03 - 3 mg/mL) inhibitory effect on K+-induced contractions in rat stomach fundus, guinea-pig ileum and rabbit jejunum preparations. The calcium channel blocking (CCB) activity was confirmed when Ss.Cr caused a rightward shift in the Ca++ dose-response curves. It also potentiated, at lower doses (0.001 - 0.03 mg/mL), the contractile effect of a fixed dose of acetylcholine (ACh), similar to physostigmine, and suppressed the effect of ACh at higher doses (0.3 - 1.0 mg/mL). Both Ss.Cr and physostigmine inhibited acetylcholinesterase (AChE), in the in vitro assay, confirming the AChE inhibitory activity. In the in vivo studies, Ss.Cr exhibited antidiarrheal and antisecretory activities against castor oil-induced diarrhea and intestinal fluid accumulation in mice. Characteristic steroidal compounds of the plant (saracocine, saracodine, saracorine and alkaloid-C), exhibited a similar combination of AChE inhibitory and CCB activities. Thus this study provides a sound mechanistic base for some of the traditional uses of the plant in hyperactive gut states, in addition to providing the first evidence for verapamil to possess additional AChE inhibitory activity. Furthermore, these characteristic compounds with dual activity may be good candidates for further studies on their usefulness in Alzheimer’s disease.

References

  • 1 Rahman A, Choudhary M I, Khan M R, Anjum S, Farooq A, Iqbal M Z. New steroidal alkaloids from Sarcococca saligna .  Journal of Natural Products. 2000;  63 1364-8
  • 2 Kohli J M, Zaman A, Kidwai A R. Separation and characterization of the alkaloids of Sarcococca pruniformis .  Tetrahedron. 1967;  23 3829-35
  • 3 Rahman A, Feroz F, Haq Z, Nawaz S A, Khan M R, Choudhary M I. New steroidal alkaloids from Sarcococca saligna .  Natural Product Research. 2003;  17 235-41
  • 4 National Research C ouncil. Guide for the care and use of laboratory animals. Washington, DC; National Academy Press 1996: 1-7
  • 5 Gilani A H, Cobbin L B. Cardioselectivity of himbacine: a muscarinic receptor antagonist.  Naunyn Schmiedeberg’s Archives of Pharmacology. 1986;  332 16-20
  • 6 Ellman G L, Courtney K D, Andres V, Featherstone R M. A new and rapid calorimetric determination of acetylcholinesterase activity.  Biochemical Pharmacology. 1961;  7 88-95
  • 7 Izzo A A, Mascolo N, Carlo G D, Capasso F. N G-Nitro-L-arginine methyl ester modulates intestinal secretion and motility produced by carbachol.  European Journal of Pharmacology. 1994;  271 31-5
  • 8 Rao V SN, Santos F A, Sobreira T T, Souza M F, Melo C L, Silveira E R. Investigations on the gastroprotective and antidiarrhoeal properties of tertian, a tetramethoxyflavone from Egletes viscose .  Planta Medica. 1997;  63 146-9
  • 9 Karaki H, Weiss G. Mini-review: Calcium release in smooth muscles.  Life Sciences. 1988;  42 111-22
  • 10 Bolton T B. Mechanism of action of transmitters and other substances on smooth muscles.  Physiological Reviews. 1979;  59 606-718
  • 11 Staneva-Stoytcheva D, Venkova K. Effects of the calcium antagonists diltiazem, verapamil and nitrendipine on the contractile responses of guinea-pig isolated ileum to electrical stimulation or carbachol.  Journal of Pharmacy and Pharmacology. 1992;  44 21-5
  • 12 Mycek M J, Harvey R A, Champe P C. Drugs affecting the autonomic nervous system. In: Harvey RA, Champe PC, editors Lippincott’s Illustrated Reviews-Pharmacology. New York; Lippincott-Raven 1997: 27-9
  • 13 Palmer A M. Pharmacotherapy for Alzheimer’s disease: progress and prospects.  Trends in Pharmacological Sciences. 2002;  23 426-33
  • 14 Vagnucci A H, Li W W. Alzheimer’s disease and angiogenesis.  Lancet. 2003;  361 605-8
  • 15 Arrieta L, Birks J. Nimodipine for primary degenerative, mixed and vascular dementia.  The Cochrane Database of Systematic Reviews. 2001;  1 CD000147
  • 16 Iwao I, Terada Y. On the mechanism of diarrhea due to castor oil.  Japanese Journal of Pharmacology. 1962;  12 137-45
  • 17 Croci T, Landi M, Elmonds-Alt X, Le Fur G, Maffrand J P, Manara L. Role of tachykinins in castor oil induced diarrhoea in rats.  British Journal of Pharmacology. 1997;  121 375-80
  • 18 Katzka D A, Castell D O. Calcium antagonists and the gastrointestinal tract - Implications for therapy. In: Epstein M, editor Calcium antagonists in clinical medicine. Philadelphia; Hanley and Belfus Inc 1992: 231-42

Prof. Dr. Anwar-ul Hassan Gilani

Department of Biological and Biomedical Sciences

The Aga Khan University Medical College

Karachi-74800

Pakistan

Fax: +92-21-493-4294/493-2095

Email: anwar.gilani@aku.edu