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基于网络药理学、分子对接及实验验证探究芍药总苷对辐射诱导脑损伤的作用及机制

Investigation of the effects and mechanism of Total Glycosides of paeony against Radiation-Induced brain injury through network Pharmacology, molecular docking and experimental Verification.

作者信息

Zhao Zhongfang, He Xiaohan, Gan Lu, Xu Dan, Zhang Taofeng, Wang Hongyu, Cui Zhencun, Zhang Hong, Liu Bin

机构信息

School of Nuclear Science and Technology, Lanzhou University, Gansu Lanzhou 730000, China; School of Stomatology, Lanzhou University, Gansu Lanzhou 730000, China; Gansu Key Laboratory of Dental and Maxillofacial Reconstruction and Bio-intelligent Manufacturing, School of Stomatology, Lanzhou University, Gansu Lanzhou 730000, China.

School of Stomatology, Lanzhou University, Gansu Lanzhou 730000, China.

出版信息

Int Immunopharmacol. 2025 Feb 20;148:114178. doi: 10.1016/j.intimp.2025.114178. Epub 2025 Jan 30.

DOI:10.1016/j.intimp.2025.114178
PMID:
39884083
Abstract

BACKGROUND

Total glucosides of paeony (TGP), derived from the dried root of Paeonia, is a popular treatment for immune diseases. Radiation induced brain injury (RBI) is a common side effect of brain radiation therapy, but the efficacy of TGP in treating RBI remains uncertain.

PURPOSE

To evaluate the protective effects of TGP against RBI and elucidate its underlying mechanisms using pharmacological network analysis, molecular docking, and experimental validation.

METHODS

The potential targets of TGP and RBI were identified using network pharmacology. Overlapping targets were analyzed for KEGG pathway enrichment and gene ontology (GO) investigations. The therapeutic effectiveness of TGP and the precision of key target genes were assessed in the mouse model of RBI, alongside observations of behavioral changes and experimental techniques.

RESULTS

Network pharmacology identified 43 targets associated with RBI that intersect with TGP. Protein-Protein Interaction (PPI) analysis highlighted key targets, including EGFR, TNF, and IL-6. Experimental outcomes demonstrated that TGP can mitigate oxidative stress damage and inflammation while enhancing memoryand learning abilities in RBI mice. Additionally, TGP dramatically decreased the activation of astrocytes and microglia, as well as the expression of key targets like EGFR, TNF, and IL-6.

CONCLUSION

TGP effectively mitigates RBI by targeting key therapeutic targets such as EGFR, TNF, and IL-6.

摘要

背景

芍药总苷(TGP)来源于芍药干燥根,是一种常用于治疗免疫性疾病的药物。放射性脑损伤(RBI)是脑放射治疗常见的副作用,但TGP治疗RBI的疗效仍不明确。

目的

通过药理网络分析、分子对接和实验验证,评估TGP对RBI的保护作用并阐明其潜在机制。

方法

利用网络药理学确定TGP和RBI的潜在靶点。对重叠靶点进行KEGG通路富集分析和基因本体(GO)研究。在RBI小鼠模型中评估TGP的治疗效果和关键靶基因的准确性,并观察行为变化和采用实验技术。

结果

网络药理学确定了43个与RBI相关且与TGP相交的靶点。蛋白质-蛋白质相互作用(PPI)分析突出了关键靶点,包括表皮生长因子受体(EGFR)、肿瘤坏死因子(TNF)和白细胞介素-6(IL-6)。实验结果表明,TGP可减轻RBI小鼠的氧化应激损伤和炎症,同时增强其记忆和学习能力。此外,TGP显著降低星形胶质细胞和小胶质细胞的活化,以及EGFR、TNF和IL-6等关键靶点的表达。

结论

TGP通过靶向EGFR、TNF和IL-6等关键治疗靶点有效减轻RBI。

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