Periploca root oils as potent, diphenolase-selective tyrosinase inhibitors: chemotype profiling and non-competitive mechanism of 4-methoxy-2-hydroxybenzaldehyde.

IF 3.5 2区农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY

Journal of the Science of Food and Agriculture Pub Date : 2025-10-06 DOI:10.1002/jsfa.70241

Na-Hyun Lee, Hoi-Seon Lee

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引用次数: 0

Abstract

Background: Safer, plant-derived alternatives to hydroquinone are needed for managing hyperpigmentation. Steam-distilled oils of Periploca sepium (China) and Periploca angustifolia (Tunisia) were obtained in yields of 2.0 g kg^-1 (w/w) and chemically profiled as phenolic chemotypes dominated by 4-methoxy-2-hydroxybenzaldehyde (788 and 746 g kg^-1, respectively). The aldehyde was isolated at 970 g kg^-1 purity with an overall yield of 1.5 g kg^-1 for mechanistic studies.

Results: Both Periploca root oils selectively and near-completely inhibited mushroom-tyrosinase diphenolase at ≤ 50 μg mL^-1 while preserving ≥ 75% monophenolase activity at the same doses. The Chinese oil was more potent (half-maximal inhibitory concentration (IC₅₀) of 9.8 μg mL^-1)) than the Tunisian oil (IC₅₀ of 11.2 μg mL^-1), consistent with its higher 4-methoxy-2-hydroxybenzaldehyde content and lower n-alkane fraction. The purified aldehyde (970 g kg^-1) exhibited strong, non-competitive inhibition of diphenolase (IC₅₀ of 9.6 μg mL^-1; the Michaelis-Menten constant (K_m) unchanged, maximum rate of reaction (V_max) reduced) and was eight-fold more potent than arbutin under identical conditions. Structure-activity relationships indicated an optimal ortho-hydroxy/para-methoxy pharmacophore, whereas added hydroxy groups diminished potency. Acute toxicity data support a wide safety margin (oral median lethal dose (LD₅₀) > 3000 mg kg^-1 in rodents), and in silico ADMET predicted favorable dermal absorption, low cytochrome P450 inhibition liability, and cosmetic suitability.

Conclusion: Periploca sepium chemotypes, standardized to ≥ 700 g kg^-1 4-methoxy-2-hydroxybenzaldehyde and ≤ 50 g kg^-1 total n-alkanes, are potent, diphenolase-selective tyrosinase inhibitors with promising safety attributes. These findings support development as clean-label actives for skin-whitening or food anti-browning, contingent on chemotype-directed quality control, confirmation on human tyrosinase/cellular models, and comprehensive chronic safety assessment. © 2025 Society of Chemical Industry.

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作为有效的二酚酶选择性酪氨酸酶抑制剂：4-甲氧基-2-羟基苯甲醛的化学型分析和非竞争性机制。

背景：对苯二酚需要更安全的植物源替代品来治疗色素沉着。蒸汽蒸馏油的产率为2.0 g kg-1 (w/w)，化学特征为以4-甲氧基-2-羟基苯甲醛为主的酚类化学型（分别为788和746 g kg-1）。该醛的纯度为970 g kg-1，总收率为1.5 g kg-1，用于机理研究。结果：在≤50 μg mL-1的剂量下，两种根精油都能选择性和几乎完全抑制蘑菇酪氨酸酶二酚酶，同时在相同剂量下保持≥75%的单酚酶活性。中国油的半最大抑制浓度（IC50）为9.8 μg mL-1)高于突尼斯油（IC50为11.2 μg mL-1），这与突尼斯油较高的4-甲氧基-2-羟基苯甲醛含量和较低的正构烷烃含量相一致。纯化后的醛（970 g kg-1）对二酚酶表现出较强的非竞争性抑制作用（IC50为9.6 μg mL-1， Michaelis-Menten常数（Km）不变，最大反应速率（Vmax）降低），在相同条件下比熊果苷强8倍。构效关系表明，最佳的邻羟基/对甲氧基药效团，而添加羟基会降低药效团的效价。急性毒性数据支持较宽的安全范围（啮齿动物口服中位致死剂量（LD50）为3000 mg kg-1），并且在计算机上ADMET预测良好的皮肤吸收，低细胞色素P450抑制能力和化妆品适用性。结论：鬼参化学型标准化为≥700 g kg-1 4-甲氧基-2-羟基苯甲醛和≤50 g kg-1总正构烷烃，是有效的二酚酶选择性酪氨酸酶抑制剂，具有良好的安全性。这些发现支持开发作为皮肤美白或食品抗褐变的清洁标签活性物质，这取决于化学型导向的质量控制，人类酪氨酸酶/细胞模型的确认，以及全面的慢性安全性评估。©2025化学工业协会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of the Science of Food and Agriculture 工程技术-农业综合

CiteScore

8.10

自引率

4.90%

发文量

634

审稿时长

3.1 months

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