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基于转录组学和网络药理学分析，使用含醇提取物对甲状腺功能亢进症诱导的氧化应激通过 AMRK 和 PPAR 信号通路的改善作用。

Ameliorative Effect of Ethanolic against Hyperthyroidism-Induced Oxidative Stress via AMRK and PPAR Signal Pathway Using Transcriptomics and Network Pharmacology Analysis.

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.

出版信息

Int J Mol Sci. 2022 Dec 22;24(1):187. doi: 10.3390/ijms24010187.

DOI:10.3390/ijms24010187
PMID:36613632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9820381/
Abstract

(L.) Moench (EP) is a well-known botanical supplement with antioxidant characteristics. However, the effects of EP on oxidative stress induced by hyperthyroidism have not yet been studied. This study was designed to evaluate the antioxidative effect of ethanolic (EEP) on hyperthyroidism-induced oxidative stress mice using an integrated strategy combining transcriptomics with network pharmacology analysis. Firstly, a hyperthyroidism mice model was induced via thyroxine (160 mg/kg) and EEP (1, 2, or 4 g/kg) once daily for 2 weeks. Body weight, thyroid-stimulating hormones, and oxidative stress markers were tested. Secondly, EEP regulating the potential genes at transcript level were analyzed. Thirdly, a network pharmacology based on the constituents of EEP identified using UPLC-Q-TOF-MS analysis was adopted. Finally, a joint analysis was performed to identify the key pathway. The results showed that EEP significantly changed the thyroid-stimulating hormones and oxidative stress markers. Meanwhile, RT-qPCR and Western Blotting demonstrated that the mechanism of the antioxidant effect of EEP reversed the mRNA expression of EHHADH, HMGCR and SLC27A2 and the protein expression of FABP and HMGCR in AMPK and PPAR signaling pathways. This study integrates transcriptomics with network pharmacology to reveal the mechanism of ameliorative effect of EEP on hyperthyroidism-induced oxidative stress.

摘要

（L.）Moench（EP）是一种具有抗氧化特性的知名植物补充剂。然而，EP 对甲状腺功能亢进引起的氧化应激的影响尚未得到研究。本研究旨在采用转录组学与网络药理学分析相结合的综合策略，评估乙醇提取物（EEP）对甲状腺素（160mg/kg）诱导的氧化应激小鼠的抗氧化作用，EEP（1、2 或 4g/kg）每天一次，持续 2 周。测试体重、甲状腺刺激激素和氧化应激标志物。其次，分析 EEP 在转录水平调节潜在基因。第三，采用基于 UPLC-Q-TOF-MS 分析鉴定的 EEP 成分的网络药理学。最后，进行联合分析以确定关键途径。结果表明，EEP 显著改变了甲状腺刺激激素和氧化应激标志物。同时，RT-qPCR 和 Western Blotting 表明，EEP 抗氧化作用的机制通过 AMPK 和 PPAR 信号通路逆转了 EHHADH、HMGCR 和 SLC27A2 的 mRNA 表达以及 FABP 和 HMGCR 的蛋白表达。本研究将转录组学与网络药理学相结合，揭示了 EEP 改善甲状腺功能亢进引起的氧化应激的作用机制。

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