Kushenol A and 8-prenylkaempferol, tyrosinase inhibitors, derived from Sophora flavescens

Abstract

Tyrosinase is known for an enzyme that plays a key role in producing the initial precursor of melanin biosynthesis. Inhibition of the catalytic reaction of this enzyme led to some advantage such as skin-whitening and anti-insect agents. To find a natural compound with inhibitory activity towards tyrosinase, the five flavonoids of kushenol A (1), 8-prenylkaempferol (2), kushenol C (3), formononetin (4) and 8-prenylnaringenin (5) were isolated by column chromatography from a 95% methanol extract of Sophora flavescens. The ability of these flavonoids to block the conversion of L-tyrosine to L-DOPA by tyrosinase was tested in vitro. Compounds 1 and 2 exhibited potent inhibitory activity, with IC50 values less than 10 µM. Furthermore, enzyme kinetics and molecular docking analysis revealed the formation of a binary encounter complex between compounds 1–4 and the enzyme. Also, all of the isolated compounds (1–5) were confirmed to possess antioxidant activity.

A comprehensive review on tyrosinase inhibitors

“…Recently, 8-prenylkaempferol as a competitive tyrosinase inhibitor along with Kushenol A (noncompetitive) isolated from Sophora flavescens 256 , have been investigated with IC 50 values less than 10 µM. Finally, based on the literature review, many flavonol inhibitors are usually competitive inhibitors due to the 3-hydroxy-4-keto moiety of the flavonol structure, which chelates the copper in the active site 251 .…”

In vitro Anti-Inflammatory and Anti-Oxidative Stress Activities of Kushenol C Isolated from the Roots of Sophora flavescens

“…Kushenol I, kushenol C, kushenol M, leachianone A, and sophoraflavone G were shown to inhibit cytochrome P450 isoform activities in human liver microsomes [3]. Kushenol A and 8-prenylkaempferol exhibited potent tyrosinase inhibitory activities by blocking the conversion of l-tyrosine to l-DOPA by tyrosinase [4]. Despite the well-studied biological activities of S. flavescens and its compounds, very little is known about the anti-oxidant and anti-inflammatory activities of the individual active compounds in different cells of the body.…”

Sesquiterpenoids and 2-(2-phenylethyl)chromones respectively acting as α-glucosidase and tyrosinase inhibitors from agarwood of an Aquilaria plant

“…All the isolated compounds ( 1 – 16 ) were tested for the inhibitory activity against tyrosinase (T3824, Sigma-Aldrich) from mushroom according to the previously reported method 16 with slight modifications. Briefly, 130 µL of tyrosinase (50 U/mL) solvated in 50 mM phosphate buffer (pH: 6.8) were mixed with 20 µL of 2-fold serial dilutions (from 1 mM to 0.03125 mM) of compounds in DMSO, and transferred into a 96-well plate.…”

“…Additionally, 6 known 2-(2-phenylethyl)chromones were also obtained. 2-(2-Phenylethyl)chromones are structurally similar to the flavones except for presence of additional ethyl group and many flavones show intriguing tyrosinase inhibitory activity 16–18 . Tyrosinase, a rate-limiting enzyme for the melanin biosynthesis, involves in pigmentation of skin 19 , browning in fresh vegetables and fruits 20 , cuticle formation in insects 21 , 22 , and neurodegeneration associated with Parkinson’s disease 23 .…”