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小白酒草(Less.)DC. 乙醇可溶部分利尿活性的药理学机制-一项民族药理学研究。

Pharmacological mechanisms involved in the diuretic activity of the ethanol-soluble fraction of Baccharis milleflora (Less.) DC. - An ethnopharmacological investigation.

机构信息

Postgraduate Program in Pharmacology (UFPR), Federal University of Paraná, Curitiba, PR, Brazil; Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados (UFGD), Dourados, MS, Brazil; Department of Pharmaceutical Sciences, State University of Ponta Grossa (UEPG), Ponta Grossa, PR, Brazil.

Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados (UFGD), Dourados, MS, Brazil.

出版信息

J Ethnopharmacol. 2024 Dec 5;335:118629. doi: 10.1016/j.jep.2024.118629. Epub 2024 Jul 24.

DOI:10.1016/j.jep.2024.118629
PMID:39059687
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Baccharis milleflora (Less.) DC. is a plant native to Brazil that is frequently used in traditional medicine as a diuretic and antihypertensive. However, even though it is traditionally used for these purposes, its diuretic and hypotensive effects have not been fully elucidated.

AIM

Investigate the cardiorenal effects of the ethanol-soluble fraction (ESBM) of Baccharis milleflora in normotensive rats.

MATERIALS AND METHODS

Cladodes of B. milleflora were analyzed using light and scanning electron microscopy to provide anatomical data to support quality control. Subsequently, the ESBM was obtained and analyzed using LC-DAD-MS, and its components were annotated. The acute toxicity of ESBM was assessed in female Wistar rats. The acute and prolonged diuretic and hypotensive effects were then studied in Wistar rats. Finally, we assessed the mechanisms responsible for the diuretic effects of ESBM, including the activity of renal Na/K/ATPase, angiotensin-converting enzyme, and erythrocyte carbonic anhydrase. Additionally, we also investigated the involvement of bradykinin, prostaglandins, and nitric oxide.

RESULTS

From LC-DAD-MS data, thirty-three metabolites were identified from ESBM, including chlorogenic acids, glycosylated phenolic derivatives, C-glycosylated flavones, and O-glycosylated flavonols. No signs of acute toxicity were observed in female rats. The findings showed that ESBM had significant diuretic and natriuretic effects, as well as a potassium-sparing effect. The treatment with ESBM was able to significantly decrease serum levels of creatinine and malondialdehyde, and also significantly increase levels of nitrite, an indirect marker of nitric oxide bioavailability. Furthermore, pre-treatment with L-NAME abolished all diuretic effects induced by ESBM.

CONCLUSION

This study presented important morpho-anatomical and phytochemical data that support the quality control of Baccharis milleflora. The ESBM exhibited a significant diuretic and natriuretic effect following acute and seven-days repeated treatment in Wistar rats, without affecting renal potassium elimination. These effects appear to be dependent on the activation of the nitric oxide-cyclic GMP pathway. This study suggests the potential use of B. milleflora preparations in clinical situations where a diuretic effect is needed.

摘要

民族药理学相关性

Baccharis milleflora(Less.)DC. 是一种原产于巴西的植物,常用于传统医学中作为利尿剂和降压药。然而,尽管它被传统用于这些用途,但它的利尿和降压作用尚未完全阐明。

目的

研究 Baccharis milleflora 乙醇可溶部分(ESBM)对正常血压大鼠的心脏肾脏作用。

材料和方法

使用光镜和扫描电子显微镜分析 Baccharis milleflora 的茎,提供解剖学数据以支持质量控制。随后,获得 ESBM 并使用 LC-DAD-MS 进行分析,并注释其成分。在雌性 Wistar 大鼠中评估 ESBM 的急性毒性。然后在 Wistar 大鼠中研究 ESBM 的急性和长期利尿和降压作用。最后,我们评估了 ESBM 利尿作用的机制,包括肾钠钾三磷酸腺苷酶、血管紧张素转换酶和红细胞碳酸酐酶的活性。此外,我们还研究了缓激肽、前列腺素和一氧化氮的参与情况。

结果

从 LC-DAD-MS 数据中,从 ESBM 中鉴定出三十三种代谢物,包括绿原酸、糖基化酚衍生物、C-糖基化黄酮和 O-糖基化黄酮醇。雌性大鼠未出现急性毒性迹象。结果表明,ESBM 具有显著的利尿和利钠作用,以及保钾作用。ESBM 治疗可显著降低血清肌酐和丙二醛水平,同时显著增加亚硝酸盐水平,亚硝酸盐是一氧化氮生物利用度的间接标志物。此外,L-NAME 预处理可消除 ESBM 诱导的所有利尿作用。

结论

本研究提供了重要的形态解剖学和植物化学数据,支持 Baccharis milleflora 的质量控制。ESBM 在 Wistar 大鼠中进行急性和七天重复治疗后表现出显著的利尿和利钠作用,而不影响肾脏钾的排泄。这些作用似乎依赖于一氧化氮-cGMP 途径的激活。该研究表明,Baccharis milleflora 制剂在需要利尿作用的临床情况下具有潜在用途。

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