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采用非靶向代谢组学方法研究黄芩酒炙前后对急性肺损伤的作用机制。

An untargeted metabolomics approach to investigate the wine-processed mechanism of Scutellariae radix in acute lung injury.

机构信息

Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.

Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.

出版信息

J Ethnopharmacol. 2020 May 10;253:112665. doi: 10.1016/j.jep.2020.112665. Epub 2020 Feb 11.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Scutellariae radix (SR) is one of the most popular traditional Chinese medicines (TCM). Crude SR (CSR) and wine-processed SR (WSR) are the two most common commercial specifications. According to the theories of TCM, wine-processing increases the inclination and direction of SR's actions, thereby strengthening its efficacy in clearing the upper-energizer lung damp heat. The pharmacological mechanism-related research on WSR for the treatment of lung disease is limited and needs to be expanded.

AIM OF THE STUDY

The aim of this report was to identify the relevant biological pathways by assessing changes in plasma metabolites between CSR and WSR in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model, and thus, revealed the potential mechanism of wine processing in SR.

MATERIALS AND METHODS

Rats with LPS-induced ALI were treated with CSR and WSR. The contents of inflammatory cytokines and histopathological examination were determined to explore the effects of CSR and WSR. Next, the metabolic profiling of rat plasma samples was performed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Then, principal component analysis (PCA) were used to provide an overview for all of the groups and orthogonal partial least squares-discriminant analysis (OPLS-DA) was utilized to maximize the discrimination and present the differences in the metabolite between all of the groups.

RESULTS

WSR exhibited a more remarkable effect on improving ALI than CSR by reducing the levels of inflammatory factors, including nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). On the basis of UPLC-QTOF-MS technology, an unequal curative effect was revealed by nontargeting metabolomics. Sixteen biomarkers were discovered in the plasma of LPS-induced rats. Pathway analysis indicated that CSR acted on ALI by regulating the abnormal sphingolipid metabolism pathways; however, an WSR-mediated cure of ALI was linked primarily to reversing the abnormality of retinol metabolism pathways and tryptophan metabolism pathways.

CONCLUSIONS

This report examined the underlying wine-processing mechanism of SR from the perspective of plasma metabolites. In addition, this work provided a novel and valuable insight into interpretation of the processing mechanisms of TCM in a holistic way.

摘要

草药的相关性

黄芩(SR)是最受欢迎的中药(TCM)之一。生黄芩(CSR)和酒黄芩(WSR)是两种最常见的商业规格。根据中医理论,酒制可增加 SR 的作用倾向和方向,从而增强其清除上焦肺湿热的功效。关于 WSR 治疗肺病的药理机制相关研究有限,需要进一步扩展。

研究目的

本报告旨在通过评估 LPS 诱导的急性肺损伤(ALI)模型中 CSR 和 WSR 之间的血浆代谢物变化,确定相关的生物途径,从而揭示 SR 酒制的潜在机制。

材料与方法

采用 LPS 诱导的 ALI 大鼠模型,分别给予 CSR 和 WSR 进行治疗。测定炎性细胞因子含量和组织病理学检查,探讨 CSR 和 WSR 的作用。然后,采用超高效液相色谱-四极杆飞行时间质谱(UPLC-QTOF-MS)对大鼠血浆样品进行代谢组学分析。采用主成分分析(PCA)对所有组进行概述,正交偏最小二乘判别分析(OPLS-DA)用于最大限度地提高判别能力并呈现各组之间的代谢物差异。

结果

WSR 通过降低一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-8(IL-8)等炎症因子的水平,对改善 ALI 的效果比 CSR 更显著。基于 UPLC-QTOF-MS 技术,非靶向代谢组学揭示了不同的疗效。在 LPS 诱导的大鼠血浆中发现了 16 种生物标志物。通路分析表明,CSR 通过调节异常的鞘脂代谢途径作用于 ALI;然而,WSR 介导的 ALI 治疗主要与逆转视黄醇代谢途径和色氨酸代谢途径的异常有关。

结论

本报告从血浆代谢物的角度探讨了 SR 的酒制机制。此外,这项工作从整体上为解释中药炮制机制提供了新的有价值的见解。

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