甘草次酸和异尿酸原对hmgb1诱导炎症的协同作用的多光谱和分子对接研究

IF 4.6 2区化学 Q1 SPECTROSCOPY

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy Pub Date : 2025-07-21 DOI:10.1016/j.saa.2025.126726

Xuewa Jiang , Shaoyan Yi , Pingping Shen , Richa Raj , Jian Zhang , Haixia Ge

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引用次数: 0

摘要

慢性低度炎症是由循环高迁移性组盒1 （HMGB1）水平升高驱动的，在多种慢性疾病的发病机制中起着至关重要的作用。甘草次酸（Glycyrrhetinic acid， GA）和异甘草素（isoigritigenin， ISL）是甘草中具有代表性的代谢物，对hmgb1介导的慢性炎症具有强有力的调节作用。在这项研究中，我们利用多光谱、表面等离子体共振（SPR）和分子对接研究了GA和ISL与HMGB1的相互作用。荧光光谱显示，GA或ISL与HMGB1结合，导致该蛋白的静态荧光猝灭。此外，GA或ISL的结合改变了色氨酸的微环境，并不同程度地降低了HMGB1 α-螺旋含量。动态光散射（DLS）结果表明，GA诱导HMGB1复合物聚集成大颗粒，而ISL则使HMGB1复合物的粒径减小。SPR分析证实，GA和ISL与HMGB1可逆结合，Kd值分别为53.0±3.6 μM和16.3±0.5 μM。分子对接进一步阐明了GA和ISL在HMGB1上的结合方式和位点，表明GA与HMGB1的B-box结合，ISL与HMGB1的A-box结合，氢键和疏水相互作用是主要驱动力。等线图分析表明，GA和ISL联合使用对hmgb1诱导的RAW264.7细胞炎症具有显著的协同抑制作用，最佳组合比例为1:1。本研究揭示了GA和ISL通过调节HMGB1构象协同发挥抗炎作用，为甘草提取物预防慢性炎性疾病提供了新的思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Insights on the synergistic effects of glycyrrhetinic acid and isoliquiritigenin on HMGB1-induced inflammation by multi-spectroscopic and molecular docking studies

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Insights on the synergistic effects of glycyrrhetinic acid and isoliquiritigenin on HMGB1-induced inflammation by multi-spectroscopic and molecular docking studies

Chronic low-grade inflammation, driven by elevated levels of circulating high mobility group box1 (HMGB1), plays a crucial role in the pathogenesis of multiple chronic diseases. Glycyrrhetinic acid (GA) and isoliquiritigenin (ISL) are representative metabolites in licorice, exhibit potent regulatory effects on HMGB1-mediated chronic inflammation. In this research, we investigated the interactions of GA and ISL with HMGB1 using multi-spectroscopy, surface plasmon resonance (SPR), and molecular docking. Fluorescence spectroscopy revealed that GA or ISL binds to HMGB1, leading to static fluorescence quenching of the protein. Additionally, the binding of GA or ISL altered the microenvironment of tryptophan and decreased the α-helix content of HMGB1 to varying extents. Dynamic light scattering (DLS) showed that GA induced aggregation of the HMGB1 complex into large particles, while ISL reduced the particle size of HMGB1. SPR analysis confirmed that GA and ISL bound reversibly to HMGB1 with K_d values of 53.0 ± 3.6 and 16.3 ± 0.5 μM, respectively. Molecular docking further elucidated the binding modes and sites of GA and ISL on HMGB1, showing that GA binds to the B-box and ISL binds to the A-box of HMGB1, with hydrogen bonding and hydrophobic interactions as the primary driving forces. Isobologram analysis demonstrated that the combination of GA and ISL exhibited a significant synergistic inhibitory effect on HMGB1-induced inflammation on RAW264.7 cells, with an optimal combination ratio of 1:1. This study reveals that GA and ISL synergistically exert anti-inflammatory effect by modulating HMGB1 conformation, offering new insights into licorice extracts for preventing chronic inflammatory diseases.

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来源期刊

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 物理-光谱学

CiteScore

8.40

自引率

11.40%

发文量

1364

审稿时长

40 days

期刊介绍： Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy (SAA) is an interdisciplinary journal which spans from basic to applied aspects of optical spectroscopy in chemistry, medicine, biology, and materials science. The journal publishes original scientific papers that feature high-quality spectroscopic data and analysis. From the broad range of optical spectroscopies, the emphasis is on electronic, vibrational or rotational spectra of molecules, rather than on spectroscopy based on magnetic moments. Criteria for publication in SAA are novelty, uniqueness, and outstanding quality. Routine applications of spectroscopic techniques and computational methods are not appropriate. Topics of particular interest of Spectrochimica Acta Part A include, but are not limited to: Spectroscopy and dynamics of bioanalytical, biomedical, environmental, and atmospheric sciences, Novel experimental techniques or instrumentation for molecular spectroscopy, Novel theoretical and computational methods, Novel applications in photochemistry and photobiology, Novel interpretational approaches as well as advances in data analysis based on electronic or vibrational spectroscopy.