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三种大黄属植物通过调控 PI3K/AKT/NF-B 信号通路抑制血管内皮损伤的比较研究。

Comparison of Three Species of Rhubarb in Inhibiting Vascular Endothelial Injury via Regulation of PI3K/AKT/NF-B Signaling Pathway.

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.

School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China.

出版信息

Oxid Med Cell Longev. 2022 Mar 28;2022:8979329. doi: 10.1155/2022/8979329. eCollection 2022.

DOI:10.1155/2022/8979329
PMID:35387258
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8979719/
Abstract

BACKGROUND/AIM: Rhubarb, a traditional Chinese medicine derived from three species, is commonly used in the prescriptions for promoting blood circulation and removing blood stasis based on its traditional effects of removing blood stasis and dredging the meridians. It has been reported that rhubarb can protect blood vessels by reducing inflammation and inhibiting vascular endothelial injury (VEI), but the effective components and mechanism of rhubarb inhibiting VEI are still unclear. This study aimed to compare the differences in chemical compositions of the three species of rhubarb and their inhibitory effect on VEI, so as to explain the material basis and select the dominant species to inhibit VEI, and to elucidate the mechanism of rhubarb's inhibitory effect on VEI.

METHODS

Plant metabolomics was used to compare the chemical components of three species of rhubarb. The efficacy of three species of rhubarb in inhibiting VEI was compared through cell experiments . At the same time, combined with network pharmacology and molecular docking, the effective components and pathways of rhubarb involved in inhibiting VEI were screened. The mechanism of rhubarb inhibiting VEI was verified by molecular biology.

RESULTS

There were significant differences in the distribution of chemical components among the three species of rhubarb. We identified 36 different chemical components in the positive ion mode and 38 different chemical components in the negative ion mode. Subsequently, the results showed significant differences in inhibiting VEI among the three species of rhubarb based on the contents of inflammatory factors (such as IL-1, IL-6, and TNF-), ROS, and NO and confirmed that had the best inhibitory effect on VEI in the light of the comprehensive efficacy, compared with and . Three species of rhubarb alleviated the inflammatory response in LPS-induced EA.hy926 cells by reducing the contents of inflammatory cytokines IL-6, IL-1, and TNF- and decreasing expressions of PI3K, AKT, NF-B p65, and STAT3 protein in the PI3K/AKT/NF-B pathway and the inhibition of proteins phosphorylation. In addition, three species of rhubarb could lessen the contents of ROS and NO in EA.hy926 cells induced by LPS. All results indicated that the process of inflammation-induced cellular oxidative stress, which resulted in VEI, was obviously improved by three species of rhubarb.

CONCLUSION

was more effective among three species of rhubarb, and it had been proved that gallic acid, gallic-acid--galloyl-glucoside, procyanidin B-2,3,3'-di--gallatein, and other potential components could reduce the contents of inflammatory factors (such as IL-1, IL-6, and TNF-), ROS, and NO by inhibiting the PI3K/AKT/NF-B signaling pathway and protected the vascular endothelium and the blood vessels by improving the inflammation and oxidative stress reaction.

摘要

背景/目的:大黄是一种传统中药,来源于三种植物,其传统功效为活血化瘀、疏通经络,常被用于活血化瘀的方剂中。有报道称,大黄可以通过减轻炎症和抑制血管内皮损伤(VEI)来保护血管,但大黄抑制 VEI 的有效成分和机制仍不清楚。本研究旨在比较三种大黄植物化学成分的差异及其对 VEI 的抑制作用,从而解释物质基础并选择抑制 VEI 的优势种,阐明大黄抑制 VEI 的作用机制。

方法

采用植物代谢组学方法比较三种大黄植物的化学成分。通过细胞实验比较三种大黄植物抑制 VEI 的功效。同时,结合网络药理学和分子对接,筛选大黄抑制 VEI 相关的有效成分和通路。通过分子生物学验证大黄抑制 VEI 的作用机制。

结果

三种大黄植物化学成分的分布存在显著差异。在正离子模式下鉴定出 36 种不同的化学成分,在负离子模式下鉴定出 38 种不同的化学成分。随后,基于炎症因子(如 IL-1、IL-6 和 TNF-)、ROS 和 NO 的含量,我们发现三种大黄植物对 VEI 的抑制作用存在显著差异,并根据综合功效确定 对 VEI 的抑制作用最好,优于 和 。三种大黄植物通过降低 LPS 诱导的 EA.hy926 细胞中炎症因子 IL-6、IL-1 和 TNF-的含量,以及降低 PI3K/AKT/NF-B 通路中 PI3K、AKT、NF-B p65 和 STAT3 蛋白的表达,减轻 LPS 诱导的 EA.hy926 细胞的炎症反应。此外,三种大黄植物还可以降低 LPS 诱导的 EA.hy926 细胞中 ROS 和 NO 的含量。所有结果均表明,三种大黄植物可明显改善由炎症诱导的细胞氧化应激引起的 VEI 过程。

结论

三种大黄植物中,对 VE 的抑制作用最强,已证明没食子酸、没食子酸- - - 二没食子酰葡萄糖、原花青素 B-2,3,3'- 三 - - 没食子酰葡萄糖、表儿茶素没食子酸酯等潜在成分可通过抑制 PI3K/AKT/NF-B 信号通路降低炎症因子(如 IL-1、IL-6 和 TNF-)、ROS 和 NO 的含量,保护血管内皮细胞和血管,通过改善炎症和氧化应激反应来发挥作用。

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