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基于谱效关系、网络药理学和分子对接,对苗药林兜抗氧化作用的物质基础及作用机制进行了研究。

Based on Spectrum-Effect Relationship, Network Pharmacology, and Molecular Docking, the Material Basis and Mechanism of Antioxidant Effect of Miao Medicine Lindl Were Studied.

作者信息

Liu Gang, Zhou Lingli, Mu Kailang, Peng Leqiang, Ran Fei, Feng Guo, Liu Yuchen

机构信息

Guizhou University of Traditional Chinese Medicine, Guiyang 550025, Guizhou, China.

出版信息

ACS Omega. 2024 Oct 4;9(41):42199-42211. doi: 10.1021/acsomega.4c04212. eCollection 2024 Oct 15.

Abstract

Lindl (Lindl, Xuerensen in Chinese) is a traditional medicine frequently utilized by ethnic minorities; nevertheless, the chemicals responsible for these effects have not been identified. Ultraperformance liquid chromatography (UPLC) was utilized to establish the fingerprints of various origins. Free radical scavenging in 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) and 2,2-biazobis(3-ethyl-phenylpropylthiazole-6-sulfonate) diammonium salt (ABTS) assays was used to evaluate the antioxidant activity. Partial least-squares regression analysis (PLSR) and gray correlation analysis (GRA) were utilized to determine the spectral-effect relationship in order to screen the antioxidant pharmacodynamic components. The corresponding targets were obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Integrated Traditional Chinese Medicine (ITCM). Disease-related targets for antioxidants were collected from GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The PPI interaction network analysis, GO enrichment analysis, and KEGG pathway analysis were established using the online analysis platform, and Autodock software assisted in aligning the components with important targets. The fingerprint profile revealed 32 common peaks, and eight standards were identified using standard comparison, with similarity ranging from 0.920 to 0.995. The primary antioxidant components include proanthocyanidin B1, epicatechin, and proanthocyanidin B3. Important targets include EGFR, CASP3, IL6, PTGS2, and TNF. Important signaling pathways include the AGE-RAGE signaling pathways in diabetic complications, the MAPK signaling pathway, the IL-17 signaling pathway, and the pathways in cancer. The results of molecular docking technology showed that the main active ingredients of the drug could bind well to the core target. In this study, we successfully established the spectral-effect relationship of Lindl and clarified the effective substances of Lindl. Through network pharmacology and molecular docking methods, it was clear that Lindl plays an antioxidant role through multicomponent, multitarget, and multipathway synergy.

摘要

林德勒(中文名为林德勒、雪仁森)是少数民族常用的一种传统药物;然而,产生这些作用的化学成分尚未确定。采用超高效液相色谱(UPLC)建立不同产地的指纹图谱。通过1,1-二苯基-2-三硝基苯肼(DPPH)和2,2-偶氮二(3-乙基苯并噻唑啉-6-磺酸)二铵盐(ABTS)法中的自由基清除能力来评估抗氧化活性。运用偏最小二乘回归分析(PLSR)和灰色关联分析(GRA)来确定谱效关系,以筛选抗氧化药效成分。相应靶点从中药系统药理学(TCMSP)和整合中医(ITCM)中获取。抗氧化剂的疾病相关靶点从GeneCards和人类孟德尔遗传在线(OMIM)数据库中收集。使用在线分析平台进行蛋白质-蛋白质相互作用(PPI)网络分析、基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路分析,Autodock软件协助将成分与重要靶点进行对接。指纹图谱显示有32个共有峰,通过标准对照鉴定出8个标准品,相似度范围为0.920至0.995。主要抗氧化成分包括原花青素B1、表儿茶素和原花青素B3。重要靶点包括表皮生长因子受体(EGFR)、半胱天冬酶3(CASP3)、白细胞介素6(IL6)、前列腺素内过氧化物合酶2(PTGS2)和肿瘤坏死因子(TNF)。重要信号通路包括糖尿病并发症中的晚期糖基化终产物-晚期糖基化终产物受体(AGE-RAGE)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、白细胞介素-17(IL-17)信号通路以及癌症相关通路。分子对接技术结果表明,该药物的主要活性成分能与核心靶点良好结合。在本研究中,我们成功建立了林德勒的谱效关系并阐明了其有效物质。通过网络药理学和分子对接方法明确了林德勒通过多成分多靶点多途径协同发挥抗氧化作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d714/11483384/a8180fdb63ff/ao4c04212_0001.jpg

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