Inhibition of Tyrosinase and Melanogenesis by Carboxylic Acids: Mechanistic Insights and Safety Evaluation

作者：Yu-Pei Chen, Mingyu Li, Zirong Liu, Jinxiong Wu, Fangfang Chen, Shudi Zhang · 发表于：Molecules · 年份：2025 · DOI：10.3390/molecules30071642 · 被引用次数：11 · 研究领域：melanin and skin pigmentation、Biochemical Analysis and Sensing Techniques、Phytochemicals and Antioxidant Activities

It is well established that certain carboxylic acid compounds can effectively inhibit tyrosinase activity. This study investigated the mechanisms by which four carboxylic acid compounds—3-phenyllactic acid, lactic acid, L-pyroglutamic acid, and malic acid—inhibit tyrosinase and melanogenesis. IC50 values for mushroom tyrosinase inhibition ranged from 3.38 to 5.42 mM, with 3-phenyllactic acid (3.50 mM), lactic acid (5.42 mM), and malic acid (3.91 mM) exhibiting mixed-type inhibition, while L-pyroglutamic acid (3.38 mM) showed competitive inhibition, as determined by enzymatic kinetic analysis. Additionally, the acidification effects of lactic acid, L-pyroglutamic acid, and malic acid contributed to the reduction in tyrosinase activity. Furthermore, all four carboxylic acid compounds effectively inhibited DOPA auto-oxidation (IC50 = 0.38–0.66 mM), ranking in potency as follows: malic acid (0.38 mM) > lactic acid (0.57 mM) > 3-phenyllactic acid (0.63 mM) > L-pyroglutamic acid (0.66 mM). These compounds also demonstrated a dose-dependent reduction in melanin production in B16-F10 cells. Proteomic analysis further revealed that these compounds not only inhibit key proteins involved in melanin synthesis, such as tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2, but also potentially modulate other genes associated with melanogenesis and metabolism, including Pmel, Slc45a2, Ctns, Oca2, and Bace2. Network toxicology analysis indicated that these four compound...