State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, Macau University of Science and Technology, Taipa, Macau, China.
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, Macau University of Science and Technology, Taipa, Macau, China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Food Chem. 2024 Oct 15;455:139814. doi: 10.1016/j.foodchem.2024.139814. Epub 2024 May 26.
Persimmon (Diospyros kaki) leaf is widely used as a tea substitute in East Asia, offering potential health benefits. Although studies have highlighted their effects on hyperpigmentation disorders, the active components remain unidentified. This study introduces a novel approach combining LC-MS/MS-based molecular networking with AlphaFold2-enabled virtual screening to expedite the identification of bioactive components in persimmon leaf. A total of 105 compounds were identified by MS/MS analysis. Further, virtual screening identified five flavonoids with potential anti-melanogenic properties. Bioassays confirmed myricetin, quercetin, and kaempferol inhibited melanogenesis in human melanocytes in a dose-dependent manner. Biolayer interferometry assays revealed strong binding affinity between these flavonols and hsTYR, with K values of 23.26 ± 11.77 for myricetin, 12.43 ± 0.37 for quercetin, and 14.99 ± 3.80 μM for kaempferol. Molecular dynamics simulations provided insights into the binding interactions of these flavonols with hsTYR, particularly highlighting the essential role of the 3-OH group on the C-ring. This study elucidates the bioactive components responsible for the anti-melanogenic effects of persimmon leaf, supporting their use in product development.
柿子（Diospyros kaki）叶在东亚被广泛用作茶的替代品，具有潜在的健康益处。尽管已有研究强调了其对色素沉着异常的作用，但活性成分仍未确定。本研究采用基于 LC-MS/MS 的分子网络与 AlphaFold2 支持的虚拟筛选相结合的新方法，加速鉴定柿子叶中的生物活性成分。通过 MS/MS 分析鉴定出 105 种化合物。此外，虚拟筛选鉴定出五种具有潜在美白作用的类黄酮。生物测定证实，杨梅素、槲皮素和山奈酚以剂量依赖的方式抑制人黑素细胞中的黑色素生成。生物层干涉测定法显示这些黄酮醇与 hsTYR 之间具有很强的结合亲和力，杨梅素的 K 值为 23.26±11.77μM，槲皮素为 12.43±0.37μM，山奈酚为 14.99±3.80μM。分子动力学模拟提供了这些黄酮醇与 hsTYR 结合相互作用的见解，特别是突出了 C 环上 3-OH 基团的重要作用。本研究阐明了柿子叶抗黑色素形成作用的生物活性成分，支持其在产品开发中的应用。
