Identification and Molecular Mechanism of COX-2 Inhibitors From Anisodus tanguticus: Ligand Fishing, In Vitro Validation, Molecular Docking, Molecular Dynamics, and ADMET Analysis

IF 1.8 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Rong Su, Yue Wang, Nixia Tan, Honglun Wang, Qi Dong
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引用次数: 0

Abstract

Anisodus tanguticus (Maxim.) Pascher has demonstrated remarkable inhibitory effects on cyclooxygenase-2 (COX-2); however, the effective substances and molecular mechanism remain ambiguous. In this study, surface plasmon resonance (SPR) ligand fishing technology coupled with UPLC-Q-TOF-MS analysis were applied to identify two COX-2 binders, atropine and fabiatrin, from A. tanguticus extracts. In vitro assays verified their potent COX-2 inhibitory effects, with IC50 values of 16.63 and 10.66 mM, respectively. To elucidate the molecular mechanism underlying their inhibitory effects, we conducted molecular docking and molecular dynamics simulations. Interaction analysis revealed that both atropine and fabiatrin exhibit strong binding affinity and structural stability with COX-2. Subsequent ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions indicated that atropine and fabiatrin had favorable pharmacokinetic properties and low toxicity, suggesting their potential as anti-inflammatory agents. Notably, this is the first study to demonstrate the inhibitory effect of fabiatrin on COX-2. Overall, the integrated approach developed here provides an efficient and reliable strategy for identifying bioactive components from complex traditional Chinese medicine (TCM) systems, which may offer a new perspective and scientific basis for the research and development of naturally targeted drugs.

唐古山莨菪中COX-2抑制剂的鉴定及分子机制:配体捕捞、体外验证、分子对接、分子动力学和ADMET分析
山莨菪碱(格言)Pascher对环氧合酶-2 (COX-2)有明显的抑制作用;然而,其有效物质和分子机制尚不清楚。本研究采用表面等离子体共振(SPR)配体捕捉技术结合UPLC-Q-TOF-MS分析,对唐古古提取物中的两种COX-2结合物阿托品和fabiatrin进行了鉴定。体外实验证实了它们对COX-2的抑制作用,IC50值分别为16.63和10.66 mM。为了阐明其抑制作用的分子机制,我们进行了分子对接和分子动力学模拟。相互作用分析表明,阿托品和fabiatrin均与COX-2具有较强的结合亲和力和结构稳定性。随后的ADMET(吸收、分布、代谢、排泄和毒性)预测表明,阿托品和fabiatrin具有良好的药代动力学特性和低毒性,表明它们具有抗炎药的潜力。值得注意的是,这是第一个证明fabiatrin对COX-2抑制作用的研究。综上所述,该方法为复杂中药体系中生物活性成分的鉴定提供了一种高效、可靠的策略,为天然靶向药物的研究和开发提供了新的视角和科学依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomedical Chromatography
Biomedical Chromatography 生物-分析化学
CiteScore
3.60
自引率
5.60%
发文量
268
审稿时长
2.3 months
期刊介绍: Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.
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