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

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 

机构地区：[1]Department of Physiology,Institute of Biosciences,Sa Paulo State University(UNESP),Botucatu 18618-970,Sa Paulo,Brazil [2]Laboratory of Bioactive Compounds,Sao Francisco University,Braganca Paulista 12916-900,Sa Paulo,Brazil [3]Department of Morphology,Institute of Biosciences,Sao Paulo State University(UNESP),Botucatu 18618-970,Sao Paulo,Brazil [4]Programa de Po-graduacao em Ciecias Farmaco-ticas,Nuleo de Investigacoes Quiico-Farmaceticas(NIQFAR),Universidade do Vale do Itajai-UNIVALI,Itajai 88302-901,Santa Catarina,Brazil [5]Coastal Campus of Sa Vicente,Sa Paulo State University(UNESP),Sa Vicente 11330-900,Sa Paulo,Brazil [6]Department of Biological Science,Faculty of Sciences and Languages,Sa Paulo State University(UNESP),Assis 19806-900,SaPaulo,Brazil

出　　处：《World Journal of Gastroenterology》2018年第38期4369-4383,共15页世界胃肠病学杂志（英文版）

基　　金：Supported by the Sao Paulo Research Foundation(FAPESP),No.2015/14797-3 to Périco LL and No.2009/52237-9 to Laboratory of Biological Assays with Natural Products

摘　　要：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.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 

分 类 号：R57[医药卫生—消化系统]