Elastase inhibition by natural flavonoids: mechanistic insights and potential therapeutic applications

作者：Lihao Lin, H. Yao, Jinfeng Fu, Wenhui Zhang, Yongxue Li, Yan Wang, Haoyu Shen, Jingang Mo, Yi Guan · 发表于：Frontiers in Nutrition · 年份：2025 · DOI：10.3389/fnut.2025.1693869 · 被引用次数：5 · 研究领域：Phytochemicals and Antioxidant Activities、Protein Interaction Studies and Fluorescence Analysis、Computational Drug Discovery Methods

Overproduction of elastase plays an important role in the progression of inflammatory diseases. In this study, we compared the inhibitory effects of structurally similar bioactive flavonoids (quercetin, hyperoside, luteolin, and luteoloside) on elastase activity and elucidated their mechanisms of action. Enzyme inhibition assays and fluorescence, ultraviolet-visible (UV-vis), Fourier transform infrared (FT-IR), and circular dichroism (CD) spectroscopy examinations assessed the interactions among flavonoids, elastase, and elastase conformational changes. Molecular docking analyzed binding interactions. Thermodynamic parameters were calculated to determine the forces that stabilize the flavonoid-elastase complexes. Luteolin strongly inhibited elastase, followed by hyperoside, quercetin, and luteoloside. Fluorescence spectroscopy revealed static quenching of all flavonoids, with binding distances indicating non-radiative energy transfer between the flavonoids and elastase. Thermodynamic analysis revealed that hydrogen bonds and van der Waals forces primarily stabilized hyperoside and luteolin, whereas electrostatic interactions stabilized quercetin and luteoloside. UV-vis, FT-IR, and CD spectroscopy confirmed that flavonoids induced conformational changes in elastase, and increased random coil content was correlated with inhibitory strength. Molecular docking results supported these findings, with strong binding affinities between flavonoids and elastase, particularly luteolin a...