Identification of the Anti-ischemia-reperfusion Injury Effect of Baicalein from Scutellaria Baicalensis Georgi in Liver Transplantation.

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Junyan Liu, Shanshan Guo, Junhua Gong, Lue Cheng, Jiefu Luo, Mingxiang Cheng, Shengwei Li, Jianping Gong, Degong Jia
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引用次数: 0

Abstract

Background: The complex etiology of Ischemia-Reperfusion Injury (IRI) induced by liver transplantation (LT) and the "one-target-focused" method limit the development of effective therapeutic interventions. We aimed to reveal the specific active ingredients and mechanisms involved in the Chinese herb Scutellaria baicalensis Georgi (SBG) in alleviating IRI in LT.

Methods: The active ingredients and potential macromolecular targets of SBG were screened through related databases. The differentially expressed genes of LT were obtained from GSE151648. The protein-protein interaction network was constructed by the STRING database, and Cytoscape 3.7.1 was used to construct a compound-target-disease network. GO and KEGG enrichment analyses were performed on the DAVID database. Finally, the main active components of SBG and the corresponding mechanisms were verified in a donation after circulatory death (DCD) rat LT model.

Results: Thirty-two active ingredients of SBG and their targets were identified, and a total of 38 intersection targets were obtained. GO function and KEGG pathway enrichment analyses demonstrated that the plasma membrane and its components play an important role. Molecular docking showed baicalein, the core component of SBG, had a strong binding ability to all hub targets. Next, in DCD rats, baicalein was proven to improve liver function, alleviate pathological injury and apoptosis, and increase the survival rate. Baicalein also significantly affected the expression of 7 hub genes. Furthermore, baicalein could inhibit ferroptosis by inhibiting phospholipid peroxidation.

Conclusion: Baicalein, the main component of SBG, could alleviate IRI, affect the expression of hub genes, and inhibit ferroptosis in LT.

鉴定黄芩中的黄芩素在肝移植中抗缺血再灌注损伤的作用
背景:肝移植(LT)引起的缺血再灌注损伤(IRI)病因复杂,"单靶点 "方法限制了有效治疗干预措施的开发。我们的目的是揭示中草药黄芩(SBG)缓解肝移植IRI的特异性活性成分和机制:方法:通过相关数据库筛选黄芩的活性成分和潜在的大分子靶点。方法:通过相关数据库筛选 SBG 的有效成分和潜在大分子靶标,并从 GSE151648 中获得 LT 的差异表达基因。利用STRING数据库构建蛋白-蛋白相互作用网络,并使用Cytoscape 3.7.1构建化合物-靶标-疾病网络。在 DAVID 数据库中进行了 GO 和 KEGG 富集分析。最后,在循环死亡后捐赠(DCD)大鼠LT模型中验证了SBG的主要活性成分及其相应机制:结果:共鉴定出 32 种 SBG 活性成分及其靶点,获得 38 个交叉靶点。GO功能和KEGG通路富集分析表明,质膜及其组分发挥着重要作用。分子对接显示,SBG的核心成分黄芩素与所有枢纽靶点都有很强的结合能力。其次,黄芩苷被证明能改善 DCD 大鼠的肝功能,减轻病理损伤和细胞凋亡,提高存活率。黄芩苷还能明显影响7个中枢基因的表达。此外,黄芩苷还能通过抑制磷脂过氧化来抑制铁变态反应:结论:黄芩苷的主要成分黄芩素能缓解 LT 的 IRI,影响枢纽基因的表达,抑制铁凋亡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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