Screening and Characterizing Tyrosinase Inhibitors fromSalvia miltiorrhizaandCarthamus tinctoriusby Spectrum-Effect Relationship Analysis and Molecular Docking

Abstract

Tyrosinase (TYR) is a rate-limiting enzyme in the synthesis of melanin, while direct TYR inhibitors are a class of important clinical antimelanoma drugs. This study established a spectrum-effect relationship analysis method and high-performance liquid chromatography-mass spectrometry (LC-MS) analysis method to screen and identify the active ingredients that inhibited TYR in Salvia miltiorrhiza–Carthamus tinctorius (Danshen–Honghua, DH) herbal pair. Seventeen potential active compounds (peaks) in the extract of DH herbal pair were predicted, and thirteen of them were tentatively identified by LC-MS analysis. Furthermore, TYR inhibitory activities of five pure compounds obtained from the DH herbal pair were validated in the test in which kojic acid served as a positive control drug. Among them, three compounds including protocatechuic aldehyde, hydroxysafflor yellow A, and tanshinone IIA were verified to have high TYR inhibitory activity (IC50 value of 455, 498, and 1214 μM, resp.) and bind to the same amino acid residues in TYR catalytic pocket according to the results of the molecular docking test. However, the other two compounds lithospermic acid and salvianolic acid A had a weak effect on TYR, as they do not combine with the active amino acid residues or act on the active center of TYR. Therefore, the developed methods (spectrum-effect relationship analysis and molecular docking) could be used to effectively screen TYR inhibitors in complex mixtures such as natural products.

A comprehensive review on tyrosinase inhibitors

“…In searching effective tyrosinase inhibitors from natural products, many flavonoid compounds have been isolated and evaluated for their inhibitory activity on mushroom tyrosinase from different natural sources such as Trifolium nigrescens Subsp . Petrisavi 227 , mung bean ( Vigna radiatae L.) 228 , calamondin peel 229 , Morus yunnanensis 230 , Bhagwa and Arakta cultivar 231 , Tibouchina semidecandra L 232 , Maackia faurie 232 , Pleurotus ostreatus 233 , Potentilla bifurca 234 , Alpinia officinarum 235 , roots of Morus lhou 236 , Garcinia subelliptica 160 , Artocapus altilis 190 , Myrsine africana 237 , Pulsatilla cernua 238 , Salvia miltiorrhiza - Carthamus tinctorius (Danshen-Honghua, DH) herbal pair 239 and other various medicinal plants 240 .…”

“…The quinones are a class of small molecules that are mostly derived from aromatic compounds such as benzene or naphthalene. Among these compounds, Aloin, an anthraquinone-C-glycoside from Aloe vera 349 , anthraquinones from Polygonum cuspidatum 350 and tanshinone IIA (IC 50 = 1214 µ M) have been verified as tyrosinase inhibitors 239 .…”

Capillary electrophoresis in phytochemical analysis (2014–2017)

“…However, there might be some problems in CE‐IMER for evaluating the inhibitory potency of TCM extracts, which contain various compounds with strong UV absorption could effect on the detection of product of substrate, even though dual‐wavelength UV detection was used in some cases. A spectrum‐effect relationship analysis and LC‐MS analysis method was developed by us to screen and identify the TYR inhibitors in Salvia miltiorrhiza ‐ Carthamus tinctorius herbal pair . Among the thirteen predicted compounds, protocatechuic aldehyde, hydroxysafflor yellow A and tanshinone IIA were verified to have high TYR inhibitory activity.…”

Selecting and Characterizing Tyrosinase Inhibitors from Atractylodis macrocephalae Rhizoma Based on Spectrum-Activity Relationship and Molecular Docking

“…Tyrosinase (TYR), also nominated as polyphenol oxidase, is a polyfunctional glycosylated copper-containing enzyme which exists in the organism of animal, plant, and microorganism widely [1][2][3]. In the presence of molecular oxygen, tyrosine is firstly catalyzed by TYR to oxidize to dopa, and then further oxidized to dopaquinone, which isomerized to form dopa pigment.…”