title: Hexane Extracts ofCalophyllum brasilienseInhibit the Development of Gastric Preneoplasia inHelicobacter felisInfected INS-Gas Mice.
abstract: Objectives:Indigenous Latin American populations have used extracts fromCalophyllum brasiliense, a native hardwood, to treat gastrointestinal symptoms for generations. The hexane extract ofCalophyllum brasiliensestem bark (HECb) protects against ethanol-mediated gastric ulceration in Swiss-Webster mice. We investigated whether HECb inhibits the development of gastric epithelial pathology followingHelicobacter felisinfection of INS-Gas mice.Materials and Methods:Groups of five male, 6-week-old INS-Gas mice were colonized withH. felisby gavage. From 2 weeks after colonization their drinking water was supplemented with 2% Tween20 (vehicle), low dose HECb (33 mg/L, lHECb) or high dose HECb (133 mg/L, hHECb). Equivalent uninfected groups were studied. Animals were culled 6 weeks afterH. feliscolonization. Preneoplastic pathology was quantified using established histological criteria. Gastric epithelial cell turnover was quantified by immunohistochemistry for Ki67 and active-caspase 3. Cytokines were quantified using an electrochemiluminescence assay.Results:Vehicle-treatedH. felisinfected mice exhibited higher gastric atrophy scores than similarly treated uninfected mice (mean atrophy score 5.6 ± 0.87 SEM vs. 2.2 ± 0.58, p< 0.01). The same pattern was observed following lHECb. Following hHECb treatment,H. felisstatus did not significantly alter atrophy scores. Gastric epithelial apoptosis was not altered byH. felisor HECb administration. Amongst vehicle-treated mice, gastric epithelial cell proliferation was increased 2.8-fold in infected compared to uninfected animals (p< 0.01). Administration of either lHECb or hHECb reduced proliferation in infected mice to levels similar to uninfected mice. A Th17 polarized response toH. felisinfection was observed in all infected groups. hHECb attenuated IFN-γ, IL-6, and TNF production followingH. felisinfection [70% (p< 0.01), 67% (p< 0.01), and 41% (p< 0.05) reduction vs. vehicle, respectively].Conclusion:HECb modulates gastric epithelial pathology followingH. felisinfection of INS-Gas mice. Further studies are indicated to confirm the mechanisms underlying these observations.
authors.affiliation: Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of LiverpoolLiverpool, UK; Department of Basic Sciences in Health, Federal University of Mato GrossoMato Grosso, Brazil.
authors.forename: Larissa M S
authors.initials: LM
authors.lastname: Lemos
authors.affiliation: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of LiverpoolLiverpool, UK; Group of Neuropharmacology, Drug Research and Development Center, Federal University of CearáFortaleza, Brazil.
authors.forename: Fabio
authors.initials: F
authors.lastname: Miyajima
authors.affiliation: Department of Basic Sciences in Health, Federal University of Mato Grosso Mato Grosso, Brazil.
authors.forename: Geovane R C
authors.initials: GR
authors.lastname: Castilho
authors.affiliation: Department of Basic Sciences in Health, Federal University of Mato Grosso Mato Grosso, Brazil.
authors.forename: Domingos Tabajara O
authors.initials: DT
authors.lastname: Martins
authors.affiliation: Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool Liverpool, UK.
authors.forename: D Mark
authors.initials: DM
authors.lastname: Pritchard
authors.affiliation: Gastroenterology Research Unit, Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool Liverpool, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Burkitt
keywords: Helicobacter; chemoprevention; chromanones; preneoplasia; stomach neoplasms