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悬钩子叶提取物、馏分及两种化合物2α,3β,19α-三羟基乌苏-12-烯-28-酸和5-羟基-3,6,7,8,4'-五甲氧基黄酮对大鼠的利尿作用。

Diuretic effect of extracts, fractions and two compounds 2α,3β,19α-trihydroxy-urs-12-en-28-oic acid and 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone from Rubus rosaefolius Sm. (Rosaceae) leaves in rats.

作者信息

de Souza Priscila, Boeing Thaise, Somensi Lincon Bordignon, Cechinel-Zanchett Camile Cecconi, Bastos Jairo Kenupp, Petreanu Marcel, Niero Rivaldo, Cechinel-Filho Valdir, da Silva Luisa Mota, de Andrade Sérgio Faloni

机构信息

Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Itajaí, SC, 88302-901, Brazil.

Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, 14040-903, Brazil.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2017 Apr;390(4):351-360. doi: 10.1007/s00210-016-1333-4. Epub 2016 Dec 24.

DOI:10.1007/s00210-016-1333-4
PMID:28013356
Abstract

Although diuretics have been widely used to treat hypertension along with others cardiovascular and renal disorders, no scientific data have been recorded to support the diuretic properties of Rubus rosaefolius Sm. (Rosaceae), a plant popularly used in Brazil to treat hypertension. Male Wistar rats were orally treated with: vehicle; hydrochlorothiazide; aqueous (AERR) and methanolic (MERR) extracts; dichloromethane (DCM), hexane (HEX) and ethyl acetate (EA) fractions; and the isolated compounds 2α,3β,19α-trihydroxy-urs-12-en-28-oic acid (TUA) and 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone (PMF). At the end of the experiment (after 8 or 24 h), urine volume and other urine or plasma parameters were measured. AERR and MERR, at 100 and 30 mg/kg, respectively, induced diuretic, natriuretic and kaliuretic effect. Additionally, the DCM and HEX, but not EA, at 10 mg/kg, also increased urine volume and Na and K excretion. Both active constituents, TUA and PMF, at doses of 1 and 3 mg/kg, showed an augmented diuretic and natriuretic index. While TUA revealed a kaliuretic action, PMF did not interfere with potassium excretion. The compounds increased urinary creatinine, but not urea, levels. TUA was able to decrease calcium excretion, as well as HCTZ, while PMF effect was associated with increased urinary prostaglandin E levels. The non-selective muscarinic receptor antagonist (atropine) prevented TUA-induced diuresis. In addition, indomethacin (a cyclooxygenase inhibitor) and atropine, exhibited the ability to block the diuretic effects prompted by PMF. Our study demonstrates the diuretic effect of extracts, fractions and two natural compounds obtained from R. rosaefolius leaves in rats.

摘要

尽管利尿剂已被广泛用于治疗高血压以及其他心血管和肾脏疾病,但尚无科学数据支持巴西广泛用于治疗高血压的蔷薇科植物红泡刺藤(Rubus rosaefolius Sm.)的利尿特性。将雄性Wistar大鼠口服给予:赋形剂;氢氯噻嗪;水提取物(AERR)和甲醇提取物(MERR);二氯甲烷(DCM)、己烷(HEX)和乙酸乙酯(EA)馏分;以及分离出的化合物2α,3β,19α-三羟基乌苏-12-烯-28-酸(TUA)和5-羟基-3,6,7,8,4'-五甲氧基黄酮(PMF)。在实验结束时(8或24小时后),测量尿量以及其他尿液或血浆参数。AERR和MERR分别以100和30 mg/kg的剂量诱导利尿、利钠和利钾作用。此外,DCM和HEX(而非EA)以10 mg/kg的剂量也增加了尿量以及钠和钾的排泄。两种活性成分TUA和PMF在1和3 mg/kg的剂量下均显示出利尿和利钠指数增加。虽然TUA显示出利钾作用,但PMF不影响钾排泄。这些化合物增加了尿肌酐水平,但未增加尿素水平。TUA能够减少钙排泄,氢氯噻嗪也有此作用,而PMF的作用与尿前列腺素E水平升高有关。非选择性毒蕈碱受体拮抗剂(阿托品)可预防TUA诱导的利尿作用。此外,吲哚美辛(一种环氧化酶抑制剂)和阿托品能够阻断PMF引发的利尿作用。我们的研究证明了从红泡刺藤叶中获得的提取物、馏分和两种天然化合物在大鼠中的利尿作用。

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