Toma Walber, Gracioso Juliano de Souza, de Andrade Fábio Donisete Pezzuto, Hiruma-Lima Clélia Akiko, Vilegas Wagner, Souza Brito Alba Regina Monteiro
Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, São Paulo, Brazil.
Biol Pharm Bull. 2002 Sep;25(9):1151-5. doi: 10.1248/bpb.25.1151.
Quassia amara L., a neotropical forest shrub of the Simaroubaceae family, is widely used in Caribbean folk medicine and in some northern states of Brazil for the treatment of gastric ulcers. This plant is a source of numerous compounds including both beta-carbonile and cantin-6 alkaloids as well as, primarily, the bitter compounds known as quassinoids. We analyzed the possible antiulcerogenic activities of four extracts of different polarities: 70% ethanol (70% EtOH), 100% EtOH, 100% dichloromethane (DCM), and 100% hexane (HEX) obtained from Quassia amara bark. All extracts, administered at doses of 5000 mg/kg orally and 1000 mg/kg intraperitoneally, caused neither toxicity or death. In the indomethacin/bethanechol-induced gastric ulcer, 70% EtOH, 100% EtOH, DCM and HEX extracts, 100 mg/kg, p.o., inhibited the gastric ulcer (22.5, 23.4, 50.5, 46.8%, respectively). 70% EtOH, 100% EtOH, DCM, and HEX extracts reduced the gastric injury induced by the hypothermic restraint-stress test in mice (70.7, 80, 60, 82.7%, respectively). In the pylorus ligature of the mouse stomach, following pre-treatment with a single intraduodenal administration of 100 mg/kg of each extract, only 70% EtOH did not change the biochemical parameters of gastric juice. 100% EtOH, DCM and HEX extracts presented decreased gastric juice content, increased pH values and decreased acid output. We also determined the antiulcerogenic activity on HCl-EtOH-induced gastric ulcers in mice at four doses (25, 50, 75, 100 mg/kg, p.o.), then evaluated the possible dose-dependent relation and calculated the ED50 values. Except for 70% EtOH at a dose of 25 mg/kg, the other extracts showed significantly activity (p<0.05). The free mucous amount in the gastric stomach content was also evaluated. All extracts showed significant increases (p<0.05) of free mucous. This effect was abolished when the animals were pre-treated with indomethacin. Prostaglandin synthesis was evaluated by the administration of HEX extracts by the oral route (100 mg/kg). Prostaglandin synthesis was significantly, increased by 52.3% (p<0.05), and this effect was abolished with prior administration of indomethacin. We concluded that Quassia amara is a probable source for a new drug to treat gastric ulcers, and the mechanism of its activity relates to cytoprotective factors, such as mucous and prostaglandins, but there is still the possibility that antisecretory activity is involved in its antiulcerogenic effect.
苦木(Quassia amara L.)是苦木科一种新热带森林灌木,在加勒比民间医学以及巴西一些北部州被广泛用于治疗胃溃疡。这种植物是多种化合物的来源,包括β-羰基化合物和坎亭-6生物碱,主要是被称为苦木素类的苦味化合物。我们分析了从苦木树皮中获得的四种不同极性提取物的可能抗溃疡活性:70%乙醇(70% EtOH)、100%乙醇、100%二氯甲烷(DCM)和100%己烷(HEX)。所有提取物经口服5000 mg/kg和腹腔注射1000 mg/kg给药后,均未引起毒性或死亡。在吲哚美辛/氨甲酰甲胆碱诱导的胃溃疡中,70% EtOH、100% EtOH、DCM和HEX提取物,100 mg/kg,口服,对胃溃疡有抑制作用(分别为22.5%、23.4%、50.5%、46.8%)。70% EtOH、100% EtOH、DCM和HEX提取物减轻了小鼠低温束缚应激试验诱导的胃损伤(分别为70.7%、80%、60%、82.7%)。在小鼠胃幽门结扎实验中,每种提取物经十二指肠单次给药100 mg/kg预处理后,只有70% EtOH未改变胃液的生化参数。100% EtOH、DCM和HEX提取物呈现胃液含量降低、pH值升高和胃酸分泌减少。我们还在四个剂量(25、50、75、100 mg/kg,口服)下测定了对小鼠盐酸-乙醇诱导的胃溃疡中的抗溃疡活性,然后评估了可能的剂量依赖性关系并计算了半数有效剂量(ED50)值。除25 mg/kg剂量的70% EtOH外,其他提取物均表现出显著活性(p<0.05)。还评估了胃内容物中游离黏液的量。所有提取物均显示游离黏液显著增加(p<0.05)。当动物用吲哚美辛预处理时,这种作用被消除。通过口服途径(100 mg/kg)给予HEX提取物来评估前列腺素合成。前列腺素合成显著增加了52.3%(p<0.05),并且在预先给予吲哚美辛后这种作用被消除。我们得出结论,苦木可能是一种治疗胃溃疡新药的来源,其活性机制与细胞保护因子如黏液和前列腺素有关,但仍有可能其抗溃疡作用涉及抗分泌活性。