基于计算生物学的含何首乌中成药药物性肝损伤机制研究

doi:10.3976/j.issn.1002-4026.20240081

摘要/Abstract

摘要：

药物性肝损伤(drug-induced liver injury,DILI)是最常见的药物不良反应之一。基于计算生物学和人工智能模型探索中药复方不良反应的物质基础和作用机制,对于提升临床用药安全性具有重要意义。检索复方首乌地黄丸(CPRP)的化学成分及靶点信息和DILI相关靶点,构建CPRP-DILI蛋白-蛋白相互作用(PPI)网络包含362个节点和1 518条相互作用关系;GO分析表明CPRP-DILI在分子功能主要涉及对化学物质、化学刺激、有机物的反应等,细胞组分定位于细胞外、细胞质膜部分、细胞表面等,生物过程涉及酶、蛋白、小分子及信号受体结合等;KEGG信号通路涉及PI3K-Akt、MAPK信号通路等;miRNA调控网络涉及的关键miRNA包括hsa-mir-34a-5p、has-mir-155-5p;两个核心子网络的HubGene包括AKT1、CTNNB1、MAPK3、HIF1A、JUN、TP53、STAT3;关联临床药物主要为抗肿瘤药、非甾体抗炎药、免疫抑制剂等;预测CPRP中大黄素、大黄酸、没食子酸等14个DILI高风险化合物。复方首乌地黄丸中的化学成分可能影响易感人群某些生物途径,干扰肝脏血管新生和自噬平衡,从而减慢肝脏修复进程加重肝损伤,并可能与嘧啶类抗肿瘤药、非甾体抗炎药、免疫抑制剂等具有交叉肝毒性,提示临床与上述药物联用需要谨慎。

关键词: 药物性肝损伤, 何首乌, 复方首乌地黄丸, 计算生物学, 血管新生

Abstract:

Drug-induced liver injury (DILI) is one of the most common adverse drug reactions. Therefore, using computational biology and artificial intelligence modeling to explore the material basis and mechanisms underlying adverse drug reactions from traditional Chinese medicine compounds is of great significance in enhancing the safety of clinical medication. In this study, we retrieved the chemical composition and target information of Compound Polygonum multiflorum and Rehmannia glutinosa Pills (CPRP), along with DILI-related targets. A CPRP-DILI protein-protein interaction network containing 362 nodes and 1 518 interactions was constructed based on this information. Gene ontology analysis indicated that in terms of molecular function CPRP-DILI primarily involves reactions to chemical substances, chemical stimuli, and organic compounds. Cellular components are primarily localized to the extracellular region, plasma membrane, and cell surface. The biological processes of CPRP-DILI involve the binding of enzymes, proteins, small molecules, and signaling receptors. Kyoto encyclopedia of genes and genomes signaling pathway analysis revealed the involvement of the PI3K-Akt and MAPK signaling pathways. The key miRNAs in the miRNA regulatory network include hsa-mir-34a-5p and has-mir-155-5p. The HubGenes of the two core subnetworks include AKT1, CTNNB1, MAPK3, HIF1A, JUN, TP53, and STAT3. The clinical drugs associated with DILI include antitumor drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), and immunosuppressants. Fourteen high-risk DILI compounds were predicted to be present in CPRP, including emodin, rhein, and gallic acid. The chemical components in CPRP may affect certain biological pathways in susceptible populations, interfering with hepatic angiogenesis and autophagy balance, thereby impeding liver repair processes and exacerbating liver injury. The chemical compounds may also exhibit cross-hepatotoxicity with pyrimidine-containing antitumor drugs, NSAIDs, and immunosuppressants, suggesting that caution is needed when co-administering CPRP with the aforementioned drugs in clinical settings.

Key words: drug-induced liver injury, Polygonum multiflorum, Compound Polygonum multiflorum and Rehmannia glutinosa Pills, computational biology, angiogenesis

中图分类号:

R285

奚玮, 徐龙, 荆凡波, 曹铭晨, 李蕾, 张春辉, 邓睿童. 基于计算生物学的含何首乌中成药药物性肝损伤机制研究[J]. 山东科学, 2025, 38(4): 14-27.

XI Wei, XU Long, JING Fanbo, CAO Mingchen, LI Lei, ZHANG Chunhui, DENG Ruitong. A computational biology-based study on the mechanism of drug-induced liver injury in patients prescribed traditional Chinese medicine treatments containing Polygonum multiflorum[J]. Shandong Science, 2025, 38(4): 14-27.

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