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Gastroprotective and anti-secretory mechanisms of 2-phenylquinoline, an alkaloid isolated from Galipea longiflora.
Phytomedicine. 2017 Feb 15; 25:61-70.P

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.

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.

Authors+Show Affiliations

Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil.Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil.Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil.Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil.Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil.Instituto de Investigaciones Fármaco Bioquímicas, Facultad de Ciencias Farmacéuticas y Bioquímicas de la Universidad Mayor de San Andrés, La Paz, Bolivia.Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí, Santa Catarina, Brazil.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28190472

Citation

Breviglieri, Eduardo, et al. "Gastroprotective and Anti-secretory Mechanisms of 2-phenylquinoline, an Alkaloid Isolated From Galipea Longiflora." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 25, 2017, pp. 61-70.
Breviglieri E, Mota da Silva L, Boeing T, et al. Gastroprotective and anti-secretory mechanisms of 2-phenylquinoline, an alkaloid isolated from Galipea longiflora. Phytomedicine. 2017;25:61-70.
Breviglieri, E., Mota da Silva, L., Boeing, T., Somensi, L. B., Cury, B. J., Gimenez, A., Cechinel Filho, V., & de Andrade, S. F. (2017). Gastroprotective and anti-secretory mechanisms of 2-phenylquinoline, an alkaloid isolated from Galipea longiflora. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 25, 61-70. https://doi.org/10.1016/j.phymed.2016.12.016
Breviglieri E, et al. Gastroprotective and Anti-secretory Mechanisms of 2-phenylquinoline, an Alkaloid Isolated From Galipea Longiflora. Phytomedicine. 2017 Feb 15;25:61-70. PubMed PMID: 28190472.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gastroprotective and anti-secretory mechanisms of 2-phenylquinoline, an alkaloid isolated from Galipea longiflora. AU - Breviglieri,Eduardo, AU - Mota da Silva,Luisa, AU - Boeing,Thaise, AU - Somensi,Lincon Bordignon, AU - Cury,Benhur Judah, AU - Gimenez,Alberto, AU - Cechinel Filho,Valdir, AU - de Andrade,Sérgio Faloni, Y1 - 2016/12/24/ PY - 2016/05/16/received PY - 2016/12/19/revised PY - 2016/12/23/accepted PY - 2017/2/14/entrez PY - 2017/2/14/pubmed PY - 2017/5/18/medline KW - 2-phenylquinoline KW - Galipea longiflora KW - Gastric secretion KW - Gastric ulcer KW - Gastrin KW - Histamine SP - 61 EP - 70 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 25 N2 - 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. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/28190472/Gastroprotective_and_anti_secretory_mechanisms_of_2_phenylquinoline_an_alkaloid_isolated_from_Galipea_longiflora_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(16)30264-1 DB - PRIME DP - Unbound Medicine ER -