International journal of biological macromolecules [Int J Biol Macromol] 2025 Jun; Vol. 311 (Pt 1), pp. 143600. Date of Electronic Publication: 2025 Apr 28.

Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE

Monophenol Monooxygenase*/antagonists & inhibitors , Monophenol Monooxygenase*/chemistry , Monophenol Monooxygenase*/metabolism , Anthocyanins*/chemistry , Anthocyanins*/pharmacology , Arbutin*/chemistry , Arbutin*/pharmacology , Enzyme Inhibitors*/chemistry , Enzyme Inhibitors*/pharmacology, Molecular Docking Simulation ; Kinetics ; Hydrogen Bonding

Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare.
Natural phenolic compounds, such as anthocyanins and arbutin, have demonstrated significant potential as tyrosinase (TYR) inhibitors. However, the application of anthocyanins in biological systems is hindered by their instability under alkaline conditions, elevated temperatures, and light exposure. In contrast, arbutin exhibits superior stability while also functioning as a TYR inhibitor. To overcome these limitations, this study developed an Anthocyanin-α-Arbutin Co-amorphous (AAC) system aimed at enhancing both the stability of anthocyanins and their TYR inhibitory properties. Kinetic studies revealed that anthocyanins, arbutin, and AAC act as reversible mixed-type TYR inhibitors, with competitive inhibition as the predominant mechanism. Each compound exhibited distinct inhibition sites. Fluorescence analysis demonstrated that anthocyanins induce a fluorescence burst in TYR, likely attributed to Tyr residues, whereas α-arbutin and AAC enhance the fluorescence intensity of TYR. Moreover, α-arbutin and AAC were found to decrease the microenvironmental hydrophobicity surrounding tyrosine (Tyr) residues while increasing it around tryptophan (Trp) residues, suggesting potential conformational changes in tyrosinase. Molecular docking analysis indicated that hydrogen bonding and π-π stacking interactions occurred between anthocyanins and arbutin in the AAC system. Specifically, anthocyanins primarily interacted with TYR through π-π and π-alkyl interactions, while α-arbutin predominantly bound to TYR via hydrogen bonding. Consistent with the interaction study, α-arbutin was found to associate with tyrosinase mainly through hydrogen bonding and van der Waals forces. These findings provide novel insights into the interactions between anthocyanins and α-arbutin in the context of food science and lay a foundation for the development of innovative TYR inhibitors.
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