title: Gastroprotective and anti-secretory mechanisms of 2-phenylquinoline, an alkaloid isolated from Galipea longiflora.
abstract: 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.
  
  
  OBJECTIVE
  To evaluate the mechanisms underlying the gastroprotective effects of 2-PQ.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  2-PQ provides gastroprotection by reducing oxidative damage and inhibiting acid secretion mediated by histaminergic and gastrinergic regulatory pathways.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Breviglieri
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil.
authors.forename: Luisa
authors.initials: L
authors.lastname: Mota da Silva
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil.
authors.forename: Thaise
authors.initials: T
authors.lastname: Boeing
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil.
authors.forename: Lincon Bordignon
authors.initials: LB
authors.lastname: Somensi
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil.
authors.forename: Benhur Judah
authors.initials: BJ
authors.lastname: Cury
authors.affiliation: Instituto de Investigaciones Fármaco Bioquímicas, Facultad de Ciencias Farmacéuticas y Bioquímicas de la Universidad Mayor de San Andrés, La Paz, Bolivia.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gimenez
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil.
authors.forename: Valdir
authors.initials: V
authors.lastname: Cechinel Filho
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil. Electronic address: sfaloni@gmail.com.
authors.forename: Sérgio Faloni
authors.initials: SF
authors.lastname: de Andrade
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000897:Anti-Ulcer Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D000431:Ethanol / Q000009:adverse effects; D005744:Gastric Acid / Q000378:metabolism; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D006851:Hydrochloric Acid; D007213:Indomethacin; D008297:Male; D051379:Mice; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011804:Quinolines / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D017208:Rats, Wistar; D027821:Rutaceae / Q000737:chemistry*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C541577:2-phenylquinoline; D000470:Alkaloids; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D010936:Plant Extracts; D011804:Quinolines; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D017506:H(+)-K(+)-Exchanging ATPase; D005978:Glutathione; D006851:Hydrochloric Acid; D007213:Indomethacin
keywords: 2-phenylquinoline; Galipea longiflora; Gastric secretion; Gastric ulcer; Gastrin; Histamine