Comparative study on the interaction between fibrinogen and flavonoids

• Published in: Journal of molecular structure 2022-08, Vol.1262, p.132963, Article 132963
• Main Authors: Li, Xiangrong, Duan, Hanxiao, Song, Zhizhi, Xu, Ruonan
• Format: Article
• Language: English
• Subjects: Fibrinogen; Flavonoids; Interaction; Molecular docking; Spectroscopy
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.132963

•The quenching mechanism of fibrinogen by flavonoids is static quenching.•The binding constants between flavonoids and fibrinogen are all moderate.•Rutin or genistein has two different binding sites on fibrinogen.•Hydrophobic, electrostatic forces and hydrogen bonds are the main force types.•α-helix structure of fibrinogen decreases with the addition of flavonoids. Fibrinogen is a key component of the inflammation and clotting pathways and an established risk factor for cardiovascular disease. Flavonoids have been shown to be pharmacologically active and for many years they have been used in the treatment of many types of diseases. In this study, the interaction between flavonoids (including myricetin, rutin, naringin, hesperidin, genistein and puerarin) and fibrinogen under physiological conditions was investigated by using multiple spectroscopic and molecular docking methods. Fluorescence data reveal that the fluorescence quenching mechanism of fibrinogen by flavonoids is static quenching in the linear range. Fibrinogen has moderate affinity with flavonoids, and the binding constants (Ka) are 103–104 L mol−1. In addition, there are two different binding sites for the interaction between rutin/genistein and fibrinogen. Thermodynamic parameter analysis shows that the interaction of flavonoids and fibrinogen is synergistically driven by enthalpy and entropy, and hydrophobic interaction, electrostatic force and hydrogen bonds are the main force types. Synchronous fluorescence spectroscopy shows that rutin increases the hydrophobicity of the microenvironment around tryptophan (Trp), while the other five flavonoids have the opposite effect. Myricetin and naringin decrease the hydrophobicity of the microenvironment around tyrosine (Tyr), while the other four flavonoids have no effect on the microenvironment around Tyr. UV-vis and CD spectra show that the interaction between flavonoids and fibrinogen leads to the loosening and unfolding of fibrinogen backbone and the α-helix structure of fibrinogen decreases with the addition of flavonoids. The specific binding sites of flavonoids to fibrinogen are confirmed by molecular docking. [Display omitted]