Planta Med 2008; 74(15): 1774-1778
DOI: 10.1055/s-0028-1088336
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Myristica malabarica Heals Stomach Ulceration by Increasing Prostaglandin Synthesis and Angiogenesis

Biswanath Maity1 , Debashish Banerjee1 , Sandip K. Bandyopadhyay1 , Subrata Chattopadhyay2
  • 1Department of Biochemistry, Dr. B.C. Roy Post Graduate Institute of Basic Medical Sciences & IPGME&R, Kolkata, India
  • 2Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai, India
Further Information

Publication History

Received: March 31, 2008 Revised: August 23, 2008

Accepted: September 3, 2008

Publication Date:
18 November 2008 (online)

Abstract

Earlier we had shown that on the 3rd day of its administration to mice, indomethacin (18 mg kg−1, p. o.) produced maximum stomach ulceration with a damage score of 3.46, which was reduced by a 3-day treatment with the methanol extract of Myristica malabarica (40 mg kg−1, p. o.) and omeprazole (3 mg kg−1, p. o.) to 0.95 and 0.82, respectively. Presently, we investigated the possible role of the test samples in modulating PG synthesis and angiogenesis for their healing action. The ulceration was found to be associated with suppression of PGE2, VEGF and vWF VIII, and an increase in EGF and endostatin levels. Treatment with the plant extract reversed all these parameters accounting for its healing activity. However, despite providing similar healing, omeprazole did not alter these parameters.

Abbreviations

EGF:epidermal growth factor

PG:prostaglandin

BEGF:vascular endothelial growth factor

vWF:von Willebrand factor

K:kinetin

AS:adenine sulfate

References

  • 1 Dr. K. M. Nadkarni’s Indian Materia Medica. Mumbai; Popular Prakashan 1954
  • 2 Palani V, Senthilkumaran R K, Govindasamy S. Biochemical evaluation of antitumor effect of muthu maranthu (a herbal formulation) on experimental fibrosarcoma in rats.  J Ethnopharmacol. 1999;  65 257-65.
  • 3 Patro B S, Bauri A K, Mishra S, Chattopadhyay S. Antioxidant activity of Myristica malabarica extracts and their constituents.  J Agric Food Chem. 2005;  53 6912-8.
  • 4 Khanom F, Kayahara H, Tadasa K. Superoxide-scavenging and prolyl endopeptidase inhibitory activities of Bangladeshi indigenous medicinal plants.  Biosci Biotechnol Biochem. 2000;  64 837-40.
  • 5 Banerjee D, Maity B, Bandyopadhyay S K, Bauri A K, Chattopadhyay S. Gastroprotective properties of Myristica malabarica against indomethacin-induced stomach ulceration: a mechanistic exploration.  J Pharm Phamacol. 2007;  59 1555-65.
  • 6 Banerjee D, Bauri A K, Guha R K, Bandyopadhyay S K, Chattopadhyay S. Healing properties of malabaricone B and malabaricone C, against indomethacin-induced gastric ulceration and mechanism of action.  Eur J Pharmacol. 2008;  578 300-12
  • 7 Miller T A. Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms.  Am J Physiol. 1983;  245 G601-G23.
  • 8 McGrath M H, Emery J MI. The effect of inhibition of angiogenesis in granulation tissue on wound healing and the fibroblast.  Ann Plast Surg. 1985;  15 106-19.
  • 9 Ma L, Soldato P D, Wallace J L. Divergent effects of new cyclooxygenase inhibitors on gastric ulcer healing: Shifting the angiogenic balance.  Proc Natl Acad Sci USA. 2002;  99 13 243-7.
  • 10 Yokoi K, Thaker P H, Robert S Y, Rebhun R, Nam D H, He J. et al . Dual inhibition of epidermal growth factor receptor and vascular endothelial growth factor receptor phosphorylation by AEE 788 reduces growth and metastasis of human colon carcinoma in an orthotopic nude mouse model.  Cancer Res. 2005;  65 3716-25.
  • 11 Weidner N, Semple J P, Welch W R, Folkman J. Tumor angiogenesis and metastasis: correlation in invasive breast carcinoma.  New Engl J Med. 1991;  324 1-8
  • 12 Wallace J L. Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years.  Gastroenterology. 1997;  112 1000-16.
  • 13 Halter F, Schamassman A, Peskar B M, Tarnawski A S. Cyclooxygenase-2 implications on maintenance of gastric mucosal integrity and ulcer healing: controversies and perspectives.  Gut. 2001;  49 443-53
  • 14 Jones M K, Wang H, Peskar B M, Levin E, Itani R M, Sarfeh I J. et al . Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing.  Nat Med. 1999;  5 1418-23
  • 15 Wallace J L. Recent advances in gastric ulcer therapeutics.  Curr Opin Pharmacol. 2005;  5 573-7
  • 16 Hassan S, Kinoshita Y, Min D, Nakata H, Kishi K, Matsushima Y. et al . Presence of prostaglandin EP4 receptor gene expression in a rat gastric mucosal cell line.  Digestion. 1996;  57 196-200
  • 17 Schmassmann A. Mechanisms of ulcer healing and effects of nonsteroidal anti-inflammatory drugs.  Am J Med. 1998;  104 43S-51S
  • 18 Coffey R J, Romano M, Goldenring J. Roles for transforming growth factor-alpha in the stomach.  J Clin Gastroenterol. 1995;  2 ( 1) S36-9
  • 19 Pai R, Tarnawski A S. Signal transduction cascades triggered by EGF Receptor activation: relevance to gastric injury repair and ulcer healing.  Dig Dis Sci. 1998;  43 (9 Suppl.) 14S-22S
  • 20 Szabo S, Vincze A. Growth factors in ulcer healing: lessons from recent studies.  J Physiol (London). 2000;  94 77-81
  • 21 O’Reilly M S, Boehm T, Shing Y, Fukai N, Vasios G, Lane W S. et al . Endostatin: An endogenous. inhibitor of angiogenesis and tumour growth.  Cell. 1997;  88 277-85
  • 22 Yamaguchi N, Anand-Apte B, Lee M, Sasaki T, Fukai N, Shapiro R. et al . Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding.  EMBO J. 1999;  18 4414-23
  • 23 Dejana E, Lampugnani M G, Giorgi M, Gaboli M, Federici A B, Ruggeri Z M. et al . Von Willebrand factor promotes endothelial cell adhesion via an Arg-Gly-Asp-dependent mechanism.  J Cell Biol. 1989;  109 367-75
  • 24 Ma L, Del Soldato P, Wallace L. Divergent effects of new cyclooxigenase inhibitors on gastric ulcer healing: shifting the angiogenic balance.  Proc Natl Acad Sci USA. 2002;  99 13 243-7
  • 25 Han J A, Ha K S, Kwon Y G, Kim Y M. Prostaglandin E2 stimulates angiogenesis by activating the nitric oxide/cGMP pathway in human umbilical vein endothelial cells.  Exp Mol Med. 2005;  37 588-600
  • 26 Schmassmann A, Peskar B M, Stettler C, Netzer P, Stroff T, Flogerzi B. et al . Effects of inhibition of prostaglandin endoperoxide synthase-2 in chronic gastro-intestinal ulcer models in rats.  Br J Pharmacol. 1998;  123 795-804
  • 27 Miura S, Tatsuguchi A, Wada K, Takeyama H, Shinji Y, Hiratsuka T. et al . Cyclooxygenase-2-regulated vascular endothelial growth factor release in gastric fibroblasts.  Am J Physiol Gastrointest Liver Physiol. 2004;  287 G444-G51
  • 28 Ng K M, Cho C H, Chang F Y, Luo J C, Lin H C, Lin H Y. et al . Omeprazole promotes gastric epithelial cell migration.  J Pharm Pharmacol. 2008;  60 655-60

Dr. Subrata Chattopadhyay

Bio-Organic Division

Bhabha Atomic Research Centre

Mumbai – 400 085

India

Phone: +91-22-2559-3703

Fax: +91-22-2550-5151

Email: schatt@barc.gov.in

>