Ellagic acid facilitates indomethacin-induced gastric ulcer healing via COX-2 up-regulation

Abstract

The mechanism of indomethacin-induced gastric ulcer healing by ellagic acid (EA) in experimental mice model is described in our study. Ulcer index (UI) and myeloperoxidase (MPO) activity of the stomach tissues showed maximum ulceration on the third day after indomethacin (18 mg/kg, single dose) administration. Preliminary observation of UI and MPO activity suggests that EA possesses ulcer-healing activity. Other anti-ulcer parameters such as the levels of prostaglandin E(2), cyclooxygenase (COX) 1 and 2 enzymes, anti-inflammatory cytokines [interleukin (IL)-4 and -5], pro-angiogenic factors, e.g. vascular endothelial growth factor, hepatocyte growth factor (HGF), and endothelial growth factor (EGF) were down-regulated by indomethacin. EA (7 mg/kg/day) treatment for 3 days shifted the indomethacin-induced pro-inflammatory biochemical parameters to the healing side. These activities were correlated with the ability of EA to alter the COX-2-dependent healing pathways. The ulcer-healing activity of EA was, however, compromised by pre-administration of the specific COX-2 inhibitor, celecoxib, and NS-398. Taken together, these results suggested that the EA treatment accelerates ulcer healing by inducing IL-4, EGF/HGF levels and enhances COX-2 expression.

Prostaglandin E2Up-regulation and Wound Healing Effect of the Ethanol Extract of Eriobotryae Folium in Human Keratinocyte

“…Determination of extracellular and intracellular PGE 2 levels PGE 2 has been known as an important mediator of healing of gastric ulcer, dermal wound and so on (Chatterjee et al, 2012;Yamamoto et al, 2012;Choi et al, 2013;Li et al, 2011). It is reported that 15-PGDH is inhibited by a variety of pharmacological agents including NSAIDs such as indomethacin, anti-paltelet aggregatory drugs such as panaxynol (Moustafa et al, 2013;Fujimoto et al, 1998), anti-allergic drugs such as flavonoid baicalein (Iijima et al, 1980), and so on.…”

“…After acting via its PGE 2 receptor (EPR), pericellular PGE 2 is cleared via re-uptake by PG transporter (PGT) and then rapidly metabolized by cytosolic enzyme named NAD + -dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) (Schuste, 1998). PGE 2 has been identified as an important mediator for gastric ulcer healing (Chatterjee et al, 2012;Yamamoto et al, 2012;de-Faria et al, 2012), dermal wound healing (Choi et al, 2013;Wilgus et al, 2004) and anti-fibrotic activity (Zhou et al, 2012).…”

Quercetin and Ellagic Acid in Gastric Ulcer Prevention: An Integrated Scheme of the Potential Mechanisms of Action From in Vivo Study

“…EA is able to accelerate healing in indomethacin GU model [32]. Thus, EA may promote GU healing by increasing collagen and FN production.…”

“…EA showed the ability to potentiate healing of indomethacininduced GU in mice due to its capability to reduce neutrophils infiltration. The modulation of COX-pathway by EA helps in amplifying mucosal growth factors levels and preserving the balance of pro-/antiinflammatory cytokines levels to aggravate ulcer healing [32].…”

“…Rats were allowed to adapt to these conditions for 2 weeks before the commencement of the experiment. After the acclimatization period, rats were distributed into: Group 1: Control group, Group 2: GU group induced by a single dose of aspirin (150 mg/kg b.wt) [29], Group 3: Omeprazol group which orally received Omeprazol (20 mg/kg b.wt) [30] daily for 1 week before induction of GU, Group 4: QU group which orally received Qu (50 mg/kg b.wt) [31] daily for 1 week before induction of GU, and Group 5: EA group which received orally EA (7 mg/kg b.wt) [32] daily for 1 week before induction of GU. After 6 h from aspirin administration, all animals were subjected to light anesthesia by diethyl ether according to the method of Van Herck et al [33] Then, the blood samples were collected using orbital sinus technique.…”