title: Gallic Acid Enriched Fraction of Phyllanthus emblica Potentiates Indomethacin-Induced Gastric Ulcer Healing via e-NOS-Dependent Pathway.
abstract: The healing activity of gallic acid enriched ethanolic extract (GAE) of Phyllanthus emblica fruits (amla) against the indomethacin-induced gastric ulceration in mice was investigated. The activity was correlated with the ability of GAE to alter the cyclooxygenase- (COX-) dependent healing pathways. Histology of the stomach tissues revealed maximum ulceration on the 3rd day after indomethacin (18 mg/kg, single dose) administration that was associated with significant increase in inflammatory factors, namely, mucosal myeloperoxidase (MPO) activity and inducible nitric oxide synthase (i-NOS) expression. Proangiogenic parameters such as the levels of prostaglandin (PG) E(2), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), von Willebrand Factor VIII, and endothelial NOS (e-NOS) were downregulated by indomethacin. Treatment with GAE (5 mg/kg/day) and omeprazole (3 mg/kg/day) for 3 days led to effective healing of the acute ulceration, while GAE could reverse the indomethacin-induced proinflammatory changes of the designated biochemical parameters. The ulcer healing activity of GAE was, however, compromised by coadministration of the nonspecific NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME), but not the i-NOS-specific inhibitor, L-N6-(1-iminoethyl) lysine hydrochloride (L-NIL). Taken together, these results suggested that the GAE treatment accelerates ulcer healing by inducing PGE(2) synthesis and augmenting e-NOS/i-NOS ratio.
authors.affiliation: Department of Biochemistry, University College of Medicine, I.P.G.M.E&R, 244B A.J.C. Bose Road, West Bengal, Kolkata 700020, India.
authors.forename: Ananya
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Sirshendu
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Angshuman
authors.initials: A
authors.lastname: Biswas
authors.forename: Sayanti
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Subrata
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Sandip K
authors.initials: SK
authors.lastname: Bandyopadhyay