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螺旋贝母提取物可恢复顺铂诱导的肾毒性模型中的肾功能:民族药理学用途、化学和毒理学研究。

Costus spiralis extract restores kidney function in cisplatin-induced nephrotoxicity model: Ethnopharmacological use, chemical and toxicological investigation.

机构信息

Faculdade de Farmácia, Universidade Federal de Minas Gerais, Faculdade de Farmácia, Avenida Antônio Carlos 6627, Campus Pampulha, 31.270-901, Belo Horizonte, MG, Brazil.

Universidade Federal de Minas Gerais, Faculdade de Medicina- Avenida Professor Alfredo Balena, 190, Campus Sáude, 30.130-190, Belo Horizonte, MG, Brazil.

出版信息

J Ethnopharmacol. 2022 Dec 5;299:115510. doi: 10.1016/j.jep.2022.115510. Epub 2022 Jun 27.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Costus spiralis (Jacq.). Roscoe (Costaceae) is traditionally used in Brazil for the treatment of kidney diseases such as pyelonephritis, urethra inflammation, kidney stones, and inflammatory conditions. There are reports of its use by Brazilian Indians since the 17th century when it was known as "pacocatinga." Currently, the use of the Costus species in Brazil is widespread, which was evidenced by the inclusion of the genus in the Brazilian National List of Medicinal Plants of Interest to the Unified Health System (RENISUS).

AIM OF THE STUDY

This study aimed to confirm the ethnopharmacological use of Costus spiralis in the treatment of kidney diseases, toxicity study using animal models, and the phytochemistry of the species.

MATERIALS AND METHODS

The chemical profile of Costus spiralis leaves extract (CSLE) was obtained for the hydroethanolic extract by ultra-performance liquid chromatography coupled to a mass spectrometer and ultraviolet detector with diode array (UPLC-UV/DAD-ESI-MS). The acute oral toxicity of the extract was predicted using the neutral red uptake cytotoxicity assay. Wistar rats were used in a model in vivo for confirmation of acute oral toxicity (2000 mg/kg p.o. for 14 days.) and determination of the effect on a cisplatin-induced nephrotoxicity model.

RESULTS

The analysis by UPLC-UV/DAD-ESI-MS showed that the chemical composition of the extract is mostly di-glycosylated flavones of apigenin. In the extract were identified the flavones vicenin II and schaftoside. The quantification of total flavonoids by spectrometry showed 0.880%. CSLE proved to be safe for acute oral administration (2000 mg/kg) with an IC value of 222.9 μg/mL and predicted oral toxic dose of 523.82 μg/mL in a neutral red uptake cytotoxicity assay. The absence of death allows the classification of the extract in class 5 according to OECD 423 guidelines and therefore it can be considered as a high acute safety product, which is highly relevant, considering the wide popular use of the species. In the cisplatin-induced nephrotoxicity model, C. spiralis extract (5, 15, and 30 mg/kg) significantly improved renal function, reversing almost completely the effects on plasma creatinine levels and creatinine clearance (p < 0.001).

CONCLUSIONS

This study demonstrates that oral administration of Costus spiralis extract leaves is safe and effective in restoring the renal function in rats in a cisplatin-induced nephrotoxicity. It is suggested that the observed activity is related to the flavonoids present. This hypothesis should be confirmed, and the participation of other secondary metabolites should be investigated in the future.

摘要

民族药理学相关性

Costus spiralis(Jacq.)。Roscoe(Costaceae)在巴西传统上用于治疗肾脏疾病,如肾盂肾炎、尿道炎症、肾结石和炎症性疾病。自 17 世纪以来,巴西印第安人就开始使用这种药物,当时它被称为“pacocatinga”。目前,Costus 物种在巴西的使用非常广泛,这从该属被列入巴西国家对统一卫生系统有兴趣的药用植物名录(RENISUS)中可以得到证明。

研究目的

本研究旨在证实 Costus spiralis 治疗肾脏疾病的民族药理学用途、使用动物模型进行毒性研究以及该物种的植物化学研究。

材料和方法

通过超高效液相色谱-串联质谱和紫外检测器与二极管阵列(UPLC-UV/DAD-ESI-MS)获得 Costus spiralis 叶提取物(CSLE)的水-乙醇提取物的化学特征。使用中性红摄取细胞毒性测定法预测提取物的急性口服毒性。在体内急性口服毒性模型(2000mg/kg,po,持续 14 天)和确定对顺铂诱导的肾毒性模型的影响中使用 Wistar 大鼠。

结果

UPLC-UV/DAD-ESI-MS 分析表明,提取物的化学成分主要是芹菜素的二糖苷化黄酮。在提取物中鉴定出黄酮 vicenin II 和 schaftoside。分光光度法测定总黄酮的含量为 0.880%。CSLE 在急性口服给药(2000mg/kg)时被证明是安全的,在中性红摄取细胞毒性测定中,IC 值为 222.9μg/mL,预测口服毒性剂量为 523.82μg/mL。由于没有死亡,根据 OECD 423 指南,提取物可归类为 5 类,因此可被认为是一种高急性安全性产品,这与该物种的广泛普及使用密切相关。在顺铂诱导的肾毒性模型中,C. spiralis 提取物(5、15 和 30mg/kg)显著改善肾功能,几乎完全逆转了对血浆肌酐水平和肌酐清除率的影响(p<0.001)。

结论

本研究表明,口服 Costus spiralis 叶提取物是安全有效的,可恢复顺铂诱导的肾毒性大鼠的肾功能。据推测,观察到的活性与存在的类黄酮有关。这一假设应该得到证实,并在未来研究中调查其他次生代谢物的参与。

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