别离胶囊抗肝纤维化的有效成分及分子机理:高分辨质谱分析、网络药理分析及实验验证

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Combinatorial chemistry & high throughput screening Pub Date : 2024-10-14 DOI:10.2174/0113862073338867240930031800
Kefeng Cao, Hui Jiang, Lili Zhang, Chang Fan, Zhigang Feng, Biao Li, Laicheng Song, Qun Zhang
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引用次数: 0

摘要

背景:解热镇痛胶囊(BJRGC)是治疗肝纤维化(LF)的常用中药制剂,但其具体的分子机制尚不清楚。本研究采用质谱分析、网络药理学和实验验证等方法,探讨白果甘草胶囊抗肝纤维化的机制:方法:采用超高效液相色谱-四极杆-非活性-轨道阱质谱(UHPLC-Q-Exactive-Orbitrap-MS)和网络药理学方法鉴定和筛选BJRGC抗LF的潜在成分、靶点和信号通路。通过分子对接验证了活性成分与靶点之间的相互作用。最后,利用 5-乙炔基-2'-脱氧尿苷(EDU)染色、免疫印迹(WB)和流式细胞术(FCM)进一步验证了 BJRGC 抗 LF 的机制:结果:在血清中总共鉴定出 9 种 BJRGC 的原型成分,其中大部分来自于栀子苷(Gardenia jasminoides Ellis)和茵陈蒿(Artemisia scoparia Waldst.et Kit.)中的鸢尾苷和三萜类化合物。网络药理学预测,血清中的药物原型成分大多会影响 CDK2、CDK6 和 PIK3CG 等靶点,其中关键途径是 PI3K/AKT 信号通路。分子对接表明,主要成分与关键靶蛋白具有良好的结合特性。实验结果表明,BJRGC能抑制造血干细胞的增殖,诱导细胞周期停滞,降低CDK2、CDK6和PIK3CG的蛋白表达:结论:BJRGC可通过其原型成分(如金丝桃苷、瘤苷酸和红豆杉苷)靶向抑制PI3K/AKT信号通路中CDK2、CDK6和PIK3CG的蛋白表达,从而抑制造血干细胞的增殖,从而缓解LF疾病。
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Effective Components and Molecular Mechanism of Biejiaruangan Capsule Against Liver Fibrosis: High-resolution Mass Spectrometry, Network Pharmacological Analysis and Experimental Verification.

Background: Biejiaruangan capsule (BJRGC) is a commonly used traditional Chinese medicine preparation for treating oftreating liver fibrosis (LF), but its specific molecular mechanism is unclear. This study used mass spectrometry, network pharmacology and experimental verification to explore the mechanism of BJRGC against LF.

Methods: Ultrahigh-performance liquid chromatography-quadrupole-exactive-orbitrap-mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS) and network pharmacology were employed to identify and screen the potential components, targets, and signaling pathways of BJRGC against LF. The interaction between the active ingredients and targets was validated using molecular docking. Finally, 5-ethynyl-2'-deoxyuridine (EDU) staining, western blotting (WB), and flow cytometry (FCM) were utilized to further verify the mechanism of BJRGC against LF.

Results: A total of 9 prototype components of BJRGC were identified in serum, most derived from iridoid glycosides and triterpenes in Gardenia jasminoides Ellis and Artemisia scoparia Waldst.et Kit. Network pharmacology predicts that medicine prototype components in serum mostly influence targets such as CDK2, CDK6, and PIK3CG, with the key route being the PI3K/AKT signaling pathway. Molecular docking showed that the major components have good binding properties with key target proteins. The experimental results showed that BJRGC could inhibit the proliferation of HSCs, induce cell cycle arrest and reduce the protein expression of CDK2, CDK6 and PIK3CG.

Conclusions: BJRGC can inhibit the proliferation of HSCs by targeting the protein expression of CDK2, CDK6, and PIK3CG in the PI3K/AKT signaling pathway through its prototype components, such as hyperoside, tumulosic acid, and hederagenin, thereby alleviating LF disease.

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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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