Discovery of anti-melanogenic components in persimmon (Diospyros kaki) leaf using LC-MS/MS-MN, AlphaFold2-enabled virtual screening and biological validation

  • Food Chem. 2024 May 26:455:139814. doi: 10.1016/j.foodchem.2024.139814.
Jiazheng Liu  1 ,  Ting Xu  2 ,  Jianjun Ding  3 ,  Haoyue Wen  1 ,  Jieru Meng  1 ,  Qing Liu  1 ,  Xiaomei Liu  1 ,  Wei Zhang  1 ,  Guo-Yuan Zhu  1 ,  Zhi-Hong Jiang  4 ,  Jin Gao  5 ,  Li-Ping Bai  6
Affiliations
  • 1. 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.
  • 2. 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.
  • 3. School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.
  • 4. 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. Electronic address: [email protected].
  • 5. Increasepharm (Hengqin) Institute Co., Ltd., Zhuhai, Guangdong, China. Electronic address: [email protected].
  • 6. 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. Electronic address: [email protected].
PMID: 38824735 DOI: 10.1016/j.foodchem.2024.139814
Abstract

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 KD 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.

Keywords
Anti-melanogenic; Bioactive components; Biological validation; LC-MS/MS-MN; Persimmon leaf; Virtual screening.
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