基于网络药理学和生物信息学研究莪术有效成分及治疗慢性胰腺炎的潜在靶点

Identification of Effective Components of Curcumae Rhizome and Potential Targets for Chronic Pancreatitis: A Study Based on Network Pharmacology and Bioinformatics Analyses

    摘要
  • 摘要:
    目的 采用网络药理学和生物信息学结合的方法探索莪术有效成分以及治疗慢性胰腺炎(CP)的潜在价值。
    方法 网络药理学方法筛选出莪术的有效活性成分及CP潜在治疗靶点，结合公开数据库中CP组织测序和单细胞测序数据，进一步分析这些靶点在CP中的表达丰度以及在细胞亚群中的分布情况。分子对接分析莪术的活性成分与CP相关靶点的结合情况。最后，通过单细胞测序分析这些核心靶点在PSC激活及相关通路的作用，评估莪术有效成分在CP治疗中抗炎、抗纤维化的潜力。
    结果 通过网络药理学分析识别出莪术中最有效化合物成分三萜皂苷，并确定了其与CP相关的两个治疗靶点基因：LYZ和Rxra。分子对接结果显示三萜皂苷与CP的核心靶点Rxra蛋白有着极强的结合能力(结合能达到-7.392 kcal·mol-1)。单细胞测序分析进一步表明，核心靶点Rxra基因与胰腺星状细胞(PSC)的激活密切相关，并且在PTN和TGF-β信号通路中发挥着重要作用，而这两条通路的激活在慢性炎症和纤维化进展中扮演着至关重要的角色。
    结论 莪术可能可以通过抑制PSC活化治疗CP，为CP的临床治疗提供新思路。

     

    Abstract:
    OBJECTIVE To explore the active components of Curcumae Rhizome as well as its potential value for the treatment of chronic pancreatitis (CP) using a combination of network pharmacology and bioinformatic approaches.
    METHODS Network pharmacology methods were used to screen the active ingredients of Curcumae Rhizome and potential therapeutic targets for CP, and their expression abundance and distribution in different cell types of CP were further analyzed in combination with CP tissue RNA sequencing data from publicly available databases. Molecular docking was performed to analyze the binding of the active components of Curcumae Rhizome to CP-related targets. Finally, the role of these core targets in pancreatic stellate cell (PSC) activation and related pathways was analyzed by single-cell RNA-sequencing to assess the anti-inflammatory and anti-fibrotic potential of the active ingredients of Curcumae Rhizome in CP treatment.
    RESULTS The most effective component of Curcumae Rhizome, Hederagenin, was identified by network pharmacological analysis, and its two therapeutic targets associated with CP were identified: LYZ and Rxra. Molecular docking results demonstrated that Hederagenin had an extremely strong binding capacity to the Rxra protein (affinity score = -7.392 kcal ·mol-1), a core target of CP. Single-cell RNA-sequencing analysis further demonstrated that the hub target Rxra gene was closely associated with PSC activation and played an important role in PTN and TGF-β signaling pathways, the activation of which played a crucial role in the progression of chronic inflammation and fibrosis.
    CONCLUSION Curcumae Rhizome may provide new clues for the treatment of CP by inhibiting PSC activation.

     

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