Tyrosinase inhibitory study of flavonolignans from the seeds of Silybum marianum (Milk thistle).
Bioorg Med Chem
; 27(12): 2499-2507, 2019 06 15.
Article
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| MEDLINE
| ID: mdl-30871862
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 (IC50â¯=â¯1.7-7.6⯵M) and diphenolase (IC50â¯=â¯12.1-44.9⯵M) 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 0.06-0.27â¯×â¯104â¯L·mol-1, which are well correlated with IC50s. In kinetic study, all flavonolignan (1-7) were mixed type I (KIâ¯<â¯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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Flavonoides
/
Monofenol Monooxigenasa
/
Silybum marianum
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article
Pais de publicación:
Reino Unido