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Bergenin 通过 RNA 测序揭示对异烟肼和利福平诱导的肝损伤的影响。

The Effect of Bergenin on Isonicotinic Acid Hydrazide and Rifampicin-Induced Liver Injury Revealed by RNA Sequencing.

机构信息

Pharmacology Laboratory of Prevention and Treatment of High Incidence of Disease, Guilin Medical University, Guilin 541199, China.

Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin 541199, China.

出版信息

Molecules. 2023 Jul 19;28(14):5496. doi: 10.3390/molecules28145496.

DOI:10.3390/molecules28145496
PMID:37513369
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10386747/
Abstract

Bergenin (BER), a natural component of polyphenols, has a variety of pharmacological activities, especially in improving drug metabolism, reducing cholestasis, anti-oxidative stress and inhibiting inflammatory responses. The aim of this study was to investigate the effects of BER on liver injury induced by isonicotinic acid hydrazide (INH) and rifampicin (RIF) in mice. The mice model of liver injury was established with INH (100 mg/kg)+RIF (100 mg/kg), and then different doses of BER were used to intervene. The pathological morphology and biochemical indicators of mice were detected. Meanwhile, RNA sequencing was performed to screen the differentially expressed genes and signaling pathways. Finally, critical differentially expressed genes were verified by qRT-PCR and Western blot. RNA sequencing results showed that 707 genes were significantly changed in the INH+RIF group compared with the Control group, and 496 genes were significantly changed after the BER intervention. These differentially expressed genes were mainly enriched in the drug metabolism, bile acid metabolism, Nrf2 pathway and TLR4 pathway. The validation results of qRT-PCR and Western blot were consistent with the RNA sequencing. Therefore, BER alleviated INH+RIF-induced liver injury in mice. The mechanism of BER improving INH+RIF-induced liver injury was related to regulating drug metabolism enzymes, bile acid metabolism, Nrf2 pathway and TLR4 pathway.

摘要

没食子酰基 Bergenin(BER)是多酚的一种天然成分,具有多种药理活性,尤其在改善药物代谢、减轻胆汁淤积、抗氧化应激和抑制炎症反应方面。本研究旨在探讨 BER 对异烟肼(INH)和利福平(RIF)诱导的小鼠肝损伤的作用。采用 INH(100mg/kg)+RIF(100mg/kg)建立小鼠肝损伤模型,然后用不同剂量的 BER 进行干预。检测小鼠的病理形态和生化指标。同时,进行 RNA 测序筛选差异表达基因和信号通路。最后,通过 qRT-PCR 和 Western blot 验证关键差异表达基因。RNA 测序结果显示,与对照组相比,INH+RIF 组有 707 个基因显著变化,BER 干预后有 496 个基因显著变化。这些差异表达基因主要富集在药物代谢、胆汁酸代谢、Nrf2 通路和 TLR4 通路。qRT-PCR 和 Western blot 的验证结果与 RNA 测序一致。因此,BER 缓解了 INH+RIF 诱导的小鼠肝损伤。BER 改善 INH+RIF 诱导的肝损伤的机制与调节药物代谢酶、胆汁酸代谢、Nrf2 通路和 TLR4 通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1736/10386747/117f729a9848/molecules-28-05496-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1736/10386747/78690f3e3111/molecules-28-05496-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1736/10386747/b98747406d01/molecules-28-05496-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1736/10386747/117f729a9848/molecules-28-05496-g011.jpg

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