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黄芩素通过抑制细胞凋亡和代谢紊乱来保护 PC12 细胞免受 Aβ诱导的细胞毒性。

Baicalein protects PC12 cells from Aβ-induced cytotoxicity via inhibition of apoptosis and metabolic disorders.

机构信息

Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China.

Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, PR China; College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, PR China.

出版信息

Life Sci. 2020 May 1;248:117471. doi: 10.1016/j.lfs.2020.117471. Epub 2020 Feb 26.

Abstract

AIMS

This study aimed to explore the protective effects and possible mechanisms of baicalein on Aβ-induced toxicity.

MAIN METHODS

Thioflavin-T (Th-T) dye was used to determine the effects of baicalein on Aβ aggregation in vitro. PC12 cells were stimulated with Aβ, then the effects of baicalein on apoptosis, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), mitochondrial respiratory complex I, reactive oxygen species (ROS) and nitric oxide (NO) levels were determined. Moreover, LC-MS metabolomics approach was used to detect metabolic changes induced by baicalein in Aβ-injured PC12 cells.

KEY FINDINGS

The results showed that baicalein could inhibit the aggregation of Aβ in vitro. Furthermore, pretreatment with baicalein significantly prevented Aβ-induced cell apoptosis, as manifested by increasing the levels of MMP, ATP and mitochondrial respiratory complex I, decreasing the contents of ROS and NO. LC-MS metabolomics revealed that baicalein can regulate 5 metabolites, mainly involving two metabolic pathways, arginine and proline metabolism, nicotinate and nicotinamide metabolism.

SIGNIFICANCE

Our study revealed that baicalein has a protective effect on Aβ-induced neurotoxicity in PC12 cells, which may be related to inhibition of apoptosis and metabolic disorders.

摘要

目的

本研究旨在探讨黄芩素对 Aβ诱导毒性的保护作用及其可能机制。

主要方法

采用硫代黄素-T(Th-T)染料测定黄芩素对 Aβ体外聚集的影响。用 Aβ刺激 PC12 细胞,然后测定黄芩素对细胞凋亡、线粒体膜电位(MMP)、三磷酸腺苷(ATP)、线粒体呼吸复合物 I、活性氧(ROS)和一氧化氮(NO)水平的影响。此外,采用 LC-MS 代谢组学方法检测黄芩素对 Aβ损伤的 PC12 细胞中代谢变化的影响。

主要发现

结果表明,黄芩素可抑制 Aβ在体外的聚集。此外,黄芩素预处理可显著防止 Aβ诱导的细胞凋亡,表现为 MMP、ATP 和线粒体呼吸复合物 I 水平升高,ROS 和 NO 含量降低。LC-MS 代谢组学显示,黄芩素可调节 5 种代谢物,主要涉及两条代谢途径,精氨酸和脯氨酸代谢、烟酸和烟酰胺代谢。

意义

本研究表明,黄芩素对 Aβ诱导的 PC12 细胞神经毒性具有保护作用,这可能与抑制细胞凋亡和代谢紊乱有关。

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