Gastroprotective and anti-secretory mechanisms of 2-phenylquinoline, an alkaloid isolated from Galipea longiflora

Eduardo Breviglieri, Luisa Mota da Silva, Thaise Boeing, Lincon Bordignon Somensi, Benhur Judah Cury, Alberto Gimenez, Valdir Cechinel Filho, Sérgio Faloni de Andrade

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

16 Citas (Scopus)

Resumen

Background We previously described the gastroprotective effect of 2-phenylquinoline (2-PQ), the main alkaloid isolated from the bark of Galipea longiflora (Rutaceae). However, despite the significant and promising results, the pharmacological mechanisms of the gastroprotection induced by 2-PQ have not been investigated. Purpose To evaluate the mechanisms underlying the gastroprotective effects of 2-PQ. Study design We used an in vivo mouse ulcer model and in vitro methodologies involving H⁺/K⁺-ATPase and L929 murine fibroblasts. Methods The gastroprotective activity of 2-PQ (10–100 mg/kg, orally, p.o) was assessed against gastric ulcer induced by 60% ethanol/0.03 M hydrochloric acid (HCl) in mice or that induced by indomethacin (80 mg/kg, p.o) in rats. The cytotoxicity was assessed in L929 murine fibroblasts. Ulcerated tissues were analyzed histologically, histochemically, and biochemically. The antisecretory activity of 2-PQ was evaluated in vivo and in vitro. Results 2-PQ showed no cytotoxicity, reduced the lesion area induced by ethanol/HCl (log half-maximal effective dose, ED50 = 1.507), and the histological evaluation supported these results. Furthermore, 2-PQ reduced indomethacin-induced gastric ulceration. The gastroprotection was accompanied by normalization of superoxide dismutase (SOD) and glutathione-S-transferase (GST) activity, an intense increase in reduced glutathione (GSH) levels, and reduction in lipid peroxide (LPO) and tumor necrosis factor (TNF)-α levels in the gastric mucosa. The antisecretory properties of 2-PQ were confirmed by the decreased volume and total acidity of the gastric juice, and it reduced histamine- or pentagastrin-stimulated gastric acid secretion. However, 2-PQ did not change the in vitro H⁺/K⁺-ATPase activity or the content of gastric-adhered mucous in mice. In addition, pretreatment with N-ethylmaleimide, NG-nitro-L-arginine methyl esters, yohimbine, or indomethacin reversed the gastroprotective effect of 2-PQ, suggesting nitric oxide, nonprotein sulfhydryl compounds, α-2-receptors, and prostaglandin were involved. Conclusion 2-PQ provides gastroprotection by reducing oxidative damage and inhibiting acid secretion mediated by histaminergic and gastrinergic regulatory pathways.

Idioma originalInglés
Páginas (desde-hasta)61-70
Número de páginas10
PublicaciónPhytomedicine
Volumen25
DOI
EstadoPublicada - 15 feb. 2017

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© 2016 Elsevier GmbH

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