Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats

AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia(HEEP) leaves on gastric ulcer healing.METHODS In this rat study involving males, intact(cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity.RESULTS Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males(52.44%), intact females(85.22%), and ovariectomized females(65.47%), confirming that HEEP accelerates the healing of acetic acidinduced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor(intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2(intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed.CONCLUSION In gastric ulcers, HEEP-induced healing(modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration.

Healing effects of heparin on acetic acid-induced gastric ulcers in rats

Abstract Objective To investigate whether or not heparin can accelerate the healing process of acetic acid induced gastric ulcers in rats and to identify the mechanisms for heparin to produce this effect, so that we can develop a new therapeutic application to heparin besides its traditional anticoagulant activity. Methods Male Sprague Dawley rats were used to produce acetic acid induced gastric ulcers. Heparin in the doses of 100, 500, and 1000 U/kg were administered intravenously through the tail vein once daily, starting 1 day after ulcer induction for 7 days in the dose response experiment or heparin 1000 U/kg at a time schedule of 3, 5, and 7 days in the time response study, respectively. The gastric mucosal blood flow (GMBF) was measured using a laser Doppler flowmeter under ether anesthesia. The rats were then sacrificed and the ulcer areas were measured. The gastric mucosa was then scraped for the determinations of mucosal prostaglandin E 2 (PGE 2) level and myeloperoxidase (MPO) activity. Results Heparin in the doses of 500 and 1000 U/kg accelerated the healing of acetic acid ulcers in a dose dependent manner. The highest dose of heparin also reduced the ulcer areas in a time dependent fashion. The effect was accompanied by an increase in gastric mucosal PGE 2 levels. The same dose of heparin not only decreased the gastric mucosal MPO activity but also increased the GMBF in a time related manner. Conclusions Heparin with the doses used in the present study accelerated the healing of acetic acid induced gastric ulcers in rats in a dose and time dependent manner, and this action was related to its effects to increase the levels of gastric mucosal PGE 2 and GMBF as well as to decrease the gastric mucosal MPO activity.