Tyrosinase inhibitory study of flavonolignans from the seeds of Silybum marianum (Milk thistle)

• Published in: Bioorganic & medicinal chemistry Vol. 27; no. 12; pp. 2499 - 2507
• Main Authors: Kim, Ji Yeong, Kim, Jeong Yoon, Jenis, Janar, Li, Zuo Peng, Ban, Yeong Jun, Baiseitova, Aizhamal, Park, Ki Hun
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-06-2019
• Subjects: Binding affinity; Chromatography, High Pressure Liquid; Flavonoids - analysis; Flavonoids - chemistry; Flavonoids - metabolism; Flavonolignans; Kinetics; Lag time; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - metabolism; Oxidation-Reduction; Plant Extracts - chemistry; Seeds - chemistry; Seeds - metabolism; Silybum marianum; Silybum marianum - chemistry; Silybum marianum - metabolism; Silymarin - analogs & derivatives; Silymarin - analysis; Silymarin - metabolism; Spectrometry, Mass, Electrospray Ionization; Substrate Specificity; Tyrosinase inhibition; Tyrosine - chemistry; Tyrosine - metabolism; Tyrosinase inhibition; Flavonolignans; Lag time; Binding affinity; Silybum marianum
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2019.03.013

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•Milk thistle has a potent potential to tyrosinase inhibition.•First report on full characterization of tyrosinase inhibition by silymarin.•A long prolongation of lag time indicated that silymarin formed Emet·I effectively.•Tyrosinase inhibition of silymarin was doubly confirmed by HPLC analysis.
Anti-melanogenesis effects of silymarin from milk thistle have been reported recently, but detailed tyrosinase inhibition properties of individual components have not been investigated. This study purported to substantiate tyrosinase inhibition and its mechanism based on a single metabolite. The responsible components for tyrosinase inhibition of target source were found out as flavonolignans which consist of isosilybin A (1), isosilybin B (2), silydianin (3), 2,3-dihydrosilychristin (4), silychristin A (5), silychristin B (6) and silybin (7), respectively. The isolated flavonolignans (1–7) inhibited both monophenolase (IC50 = 1.7–7.6 µM) and diphenolase (IC50 = 12.1–44.9 µM) of tyrosinase significantly. Their inhibitions were 10-fold effective in comparison with their mother skeletons (8–10). Inhibitory functions were also proved by HPLC analysis using N-acetyl-l-tyrosine as substrate. The predominant formation of Emet·I was confirmed from a long prolongation of lag time and a decrease of the static state activity of the enzyme. All tested compounds had a significant binding affinity to tyrosinase with KSV values of 0.06–0.27 × 104 L·mol−1, which are well correlated with IC50s. In kinetic study, all flavonolignan (1–7) were mixed type I (KI < KIS) inhibitors, whereas their mother skeletons (8–10) were competitive ones. The UPLC-ESI-TOF/MS analysis showed that the isolated inhibitors are the most abundant metabolites in the target plant.