1. Academic Validation
  2. Gastroprotective properties of Lupeol-derived ester: Pre-clinical evidences of Lupeol-stearate as a potent antiulcer agent

Gastroprotective properties of Lupeol-derived ester: Pre-clinical evidences of Lupeol-stearate as a potent antiulcer agent

  • Chem Biol Interact. 2020 Apr 25;321:108964. doi: 10.1016/j.cbi.2020.108964.
Lincon Bordignon Somensi 1 Philipe Costa 1 Thaise Boeing 1 Luísa Nathália Bolda Mariano 1 Bruna Longo 1 Cássia Gonçalves Magalhães 2 Lucenir Pain Duarte 3 Aline Teixeira Maciel E Silva 3 Priscila de Souza 1 Sérgio Faloni de Andrade 1 Luisa Mota da Silva 4
Affiliations

Affiliations

  • 1 Programa de Pós-Graduação Em Ciências Farmacêuticas (PPGCF), Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade Do Vale Do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil.
  • 2 Departamento de Química, Centro de Ciências Exatas e Naturais, Universidade Estadual de Ponta Grossa, Ponta Grossa, Paraná, Brazil.
  • 3 Departamento de Química, Centro de Ciências Exatas e Naturais, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
  • 4 Programa de Pós-Graduação Em Ciências Farmacêuticas (PPGCF), Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade Do Vale Do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil. Electronic address: luisa@univali.br.
Abstract

Lupeol (1) was isolated from hexane branch extract of Maytenus salicifolia and the Lupeol stearate (2), Lupeol palmitate (3), Lupeol myristate (4), Lupeol laurate (5) and Lupeol caprylate (6) were obtained reacting 1 with an adequate carboxylic acid. Swiss mice were treated with vehicle, carbenoxolone or Lupeol esters before administration of ethanol/HCl or indomethacin. Additionally, the involvement of nitric oxide (NO), sulfhydryl compounds (NP-SH), α-2 adrenergic receptors (α2-AR) and prostaglandins (PGE) in antiulcer effects was investigated using appropriate inhibitors or antagonist. Oxidative and inflammatory parameters were measured after euthanasia and anti-secretory effects was evaluated in pylorus-ligated rats. Ethanol/HCl ulcerated the gastric mucosa by 64.45 ± 6.58 mm2, which the oral treatment with 1, 4 and 6 (10 mg/kg), and 3 and 5 (30 mg/kg) reduced the lesion area. Interestingly, 2 reduced the gastric ulcer by oral route in a potent and dose-dependent manner (ED50 = 0.40 mg/kg), which was accompanied by the increase in reduced glutathione levels and by the reduction of lipids peroxidation and myeloperoxidase and superoxide dismutase activities. Moreover, 2 (0.1 mg/kg) also prevented the ulcerogenesis by intraperitoneal route. The participation of NO, NP-SH, α2-AR and PGE in 2-mediated gastroprotection was confirmed. In indomethacin-induced ulcer, 2 (1 mg/kg, p.o) also reduced the ulcer area and increased the PGE2 levels. However, 2 did not alter the gastric acid secretion. Therefore, these findings indicate that the obtention of 2 potentiated the antiulcer activity of 1 and that this compound can elicit gastroprotective action due a diversified mode of action.

Keywords

Esterification; Gastric healing; Oxidative stress; Semisynthetic compounds.

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