Prado Ligia Carolina da Silva, Silva Denise Brentan, de Oliveira-Silva Grasielle Lopes, Hiraki Karen Renata Nakamura, Canabrava Hudson Armando Nunes, Bispo-da-Silva Luiz Borges
Laboratory of Pharmacology, Institute of Biomedical Sciences, Federal University of Uberlândia.
Biol Pharm Bull. 2014;37(5):722-30. doi: 10.1248/bpb.b13-00514.
We applied a taxonomic approach to select the Eugenia dysenterica (Myrtaceae) leaf extract, known in Brazil as "cagaita," and evaluated its gastroprotective effect. The ability of the extract or carbenoxolone to protect the gastric mucosa from ethanol/HCl-induced lesions was evaluated in mice. The contributions of nitric oxide (NO), endogenous sulfhydryl (SH) groups and alterations in HCl production to the extract's gastroprotective effect were investigated. We also determined the antioxidant activity of the extract and the possible contribution of tannins to the cytoprotective effect. The extract and carbenoxolone protected the gastric mucosa from ethanol/HCl-induced ulcers, and the former also decreased HCl production. The blockage of SH groups but not the inhibition of NO synthesis abolished the gastroprotective action of the extract. Tannins are present in the extract, which was analyzed by matrix assisted laser desorption/ionization (MALDI); the tannins identified by fragmentation pattern (MS/MS) were condensed type-B, coupled up to eleven flavan-3-ol units and were predominantly procyanidin and prodelphinidin units. Partial removal of tannins from the extract abolished the cytoprotective actions of the extract. The extract exhibits free-radical-scavenging activity in vitro, and the extract/FeCl3 sequence stained gastric surface epithelial cells dark-gray. Therefore, E. dysenterica leaf extract has gastroprotective effects that appear to be linked to the inhibition of HCl production, the antioxidant activity and the endogenous SH-containing compounds. These pleiotropic actions appear to be dependent on the condensed tannins contained in the extract, which bind to mucins in the gastric mucosa forming a protective coating against damaging agents. Our study highlights the biopharmaceutical potential of E. dysenterica.
我们采用分类学方法选择了巴西名为“卡盖塔”的番樱桃(桃金娘科)叶提取物,并评估了其胃保护作用。在小鼠中评估了该提取物或甘珀酸保护胃黏膜免受乙醇/盐酸诱导损伤的能力。研究了一氧化氮(NO)、内源性巯基(SH)基团以及盐酸分泌变化对提取物胃保护作用的影响。我们还测定了提取物的抗氧化活性以及单宁对细胞保护作用的可能贡献。该提取物和甘珀酸保护胃黏膜免受乙醇/盐酸诱导的溃疡,并且前者还降低了盐酸分泌。SH基团的阻断而非NO合成的抑制消除了提取物的胃保护作用。提取物中存在单宁,通过基质辅助激光解吸/电离(MALDI)进行分析;通过碎片模式(MS/MS)鉴定的单宁为缩合型B,与多达11个黄烷-3-醇单元偶联,主要是原花青素和原飞燕草素单元。从提取物中部分去除单宁消除了提取物的细胞保护作用。该提取物在体外表现出自由基清除活性,并且提取物/氯化铁序列使胃表面上皮细胞染成深灰色。因此,番樱桃叶提取物具有胃保护作用,这似乎与盐酸分泌的抑制、抗氧化活性以及内源性含硫化合物有关。这些多效作用似乎取决于提取物中含有的缩合单宁,其与胃黏膜中的粘蛋白结合形成针对损伤剂的保护涂层。我们的研究突出了番樱桃的生物制药潜力。