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

Author(s):Show less -

Perico, Larissa Lucena ^[1] ; Rodrigues, Vinicius Peixoto ^[1] ; Ohara, Rie ^[1] ; Bueno, Gabriela ^[1] ; Alfieri Nunes, Vania Vasti ^[1] ; dos Santos, Raquel de Cassia ^[2] ; Lima Camargo, Ana Carolina ^[3] ; Justulin Junior, Luis Antonio ^[3] ; de Andrade, Sergio Faloni ^[4] ; Bispo Steimbach, Viviane Miranda ^[4] ; da Silva, Luisa Mota ^[4] ; Machado da Rocha, Lucia Regina ^[1] ; Vilegas, Wagner ^[5] ; dos Santos, Catarina ^[6] ; Hiruma-Lima, Clelia Akiko ^[1]

Affiliation

^[1] Sao Paulo State Univ, Inst Biosci, Dept Physiol, UNESP, BR-18618970 Botucatu, SP - Brazil

^[2] Sao Francisco Univ, Lab Bioact Compounds, BR-12916900 Braganca Paulista, SP - Brazil

^[3] Sao Paulo State Univ, UNESP, Dept Morphol, Inst Biosci, BR-18618970 Botucatu, SP - Brazil

^[4] Univ Vale Itajai UNIVALI, Nucleo Invest Quimicofarmaceut NIQFAR, Programa Posgrad Ciencias Farmaceut, BR-88302901 Itajai, SC - Brazil

^[5] Sao Paulo State Univ, UNESP, Coastal Campus Sao Vicente, BR-11330900 Sao Vicente, SP - Brazil

^[6] Sao Paulo State Univ, UNESP, Fac Sci & Languages, Dept Biol Sci, BR-19806900 Assis, SP - Brazil

• Document type: Journal article
• Source: WORLD JOURNAL OF GASTROENTEROLOGY; v. 24, n. 38, p. 4369-4383, OCT 14 2018.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 09/52237-9 - Standardized herbal medicines for the treatment of chronic diseases
• Grantee: Wagner Vilegas
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 15/14797-3 - The role of the hydroalcoholic extract from the leaves of Eugenia punicifolia (Kunth) DC on experimental peptic ulcer disease: characterization of mechanisms of action anti-inflammatory, healing and antiapoptotic.
• Grantee: Larissa Lucena Périco
• Support Opportunities: Scholarships in Brazil - Doctorate