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

World Journal of Gastroenterology 2018年第38期24卷 4369-4383页

作者： Larissa Lucena Périco Vinícius Peixoto Rodrigues Rie Ohara Gabriela Bueno Vania Vasti Alfieri Nunes Raquel Cássia dos Santos Ana Carolina Lima Camargo Luis Antuio Justulin Joior Sérgio Faloni de Andrade Viviane Miranda Bispo Steimbach Luísa Mota da Silva Lúcia Regina Machado da Rocha Wagner Vilegas Catarina dos Santos Clélia Akiko Hiruma-Lima Department of Physiology Institute of BiosciencesSa Paulo State University(UNESP)Botucatu 18618-970Sa PauloBrazil Laboratory of Bioactive Compounds Sao Francisco UniversityBraganca Paulista 12916-900Sa PauloBrazil Department of Morphology Institute of BiosciencesSao Paulo State University(UNESP)Botucatu 18618-970Sao PauloBrazil Programa de Po-graduacao em Ciecias Farmaco-ticas Nuleo de Investigacoes Quiico-Farmaceticas(NIQFAR)Universidade do Vale do Itajai-UNIVALIItajai 88302-901Santa CatarinaBrazil Coastal Campus of Sa Vicente Sa Paulo State University(UNESP)Sa Vicente 11330-900Sa PauloBrazil Department of Biological Science Faculty of Sciences and LanguagesSa Paulo State University(UNESP)Assis 19806-900SaPauloBrazil

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.

关键词： eugenia punicifolia Gastric ulcer healing Acetic acid Sex difference Myrtaceae Toxicity

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