Abstract
Objectives: Indigenous Latin American populations have used extracts from Calophyllum brasiliense, a native hardwood, to treat gastrointestinal symptoms for generations. The hexane extract of Calophyllum brasiliense stem bark (HECb) protects against ethanol-mediated gastric ulceration in Swiss–Webster mice. We investigated whether HECb inhibits the development of gastric epithelial pathology following Helicobacter felis infection of INS-Gas mice.Materials and Methods: Groups of five male, 6-week-old INS-Gas mice were colonized with H. felis by 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 after H. felis colonization. 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-treated H. felis infected 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. felis status did not significantly alter atrophy scores. Gastric epithelial apoptosis was not altered by H. felis or 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 to H. felis infection was observed in all infected groups. hHECb attenuated IFN-γ, IL-6, and TNF production following H. felis infection [70% (p < 0.01), 67% (p < 0.01), and 41% (p < 0.05) reduction vs. vehicle, respectively].Conclusion: HECb modulates gastric epithelial pathology following H. felis infection of INS-Gas mice. Further studies are indicated to confirm the mechanisms underlying these observations.
Highlights
Gastric cancer is the third commonest cause of cancer death worldwide (Ferlay et al, 2013)
We investigated whether hexane extract of Calophyllum brasiliense stem bark (HECb) inhibits the development of gastric epithelial pathology following Helicobacter felis infection of INS-Gas mice
HECb Protects against H. felis Induced Pre-neoplasia in INS-Gas Mice
Summary
Gastric cancer is the third commonest cause of cancer death worldwide (Ferlay et al, 2013). Established chemotherapeutic agents are available for patients with gastric cancer, but their efficacy is limited (Bauer et al, 2015). Another strategy that could be employed to reduce the burden of gastric cancer would be to develop chemopreventative strategies that retard the development of gastric cancer in at risk populations. The only effective treatment strategy to achieve this is to eradicate H. pylori, but this strategy is becoming more challenging due to the emergence of antibiotic resistant organisms (Shiota et al, 2015), and is relatively ineffective in people who have established preneoplastic pathology (Ford et al, 2014), novel therapeutic agents are needed. As 70% of novel chemotherapeutic agents are derived from plant materials (Newman and Cragg, 2012), the extraction and characterization of novel, naturally occurring compounds is an important strategy for the identification of potentially important new drugs
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