Correlation between the Potency of Flavonoids on Mushroom Tyrosinase Inhibitory Activity and Melanin Synthesis in Melanocytes

Abstract

Twenty-seven flavonoids isolated from Dalbergia parviflora with vast structural diversity were screened for inhibitory activity against mushroom and murine tyrosinases using l-DOPA as the substrate. Among the flavonoids tested, only four—khrinone (5), cajanin (9), (3RS)-3′-hydroxy-8-methoxy vestitol (21), and (6aR,11aR)-3,8-dihydroxy-9-methoxy pterocarpan (27)—reacted with mushroom tyrosinase, with IC50 values of 54.0, 67.9, 67.8, and 16.7 μM, respectively, and only compound 27 showed inhibitory activity against murine tyrosinase. With cell-based assays, only compounds 9 and 27 effectively inhibited melanogenesis in B16-F10 melanoma cells (by 34% and 59%, respectively), at a concentration of 15 μM, without being significantly toxic to the cells. However, the crude extract of D. parviflora and some of the flavonoid constituents appeared to increase melanin production in B16-F10 cells, suggesting that there are flavonoids with both inhibitory and stimulatory melanogenesis in the crude extract. Studies on the correlation between the enzyme-based and cell-based assays showed that only the flavonoids with IC50 values below 50 μM against mushroom tyrosinase could inhibit the mammalian tyrosinase, and thus, reduce melanogenesis in B16-F10. Flavonoids with the IC50 values greater than 50 μM, on the other hand, could not inhibit the mammalian tyrosinase, and had either no effect or enhancement of melanogenesis. In conclusion, the tyrosinase enzyme from mushroom is not as selective as the one from mammalian source for the enzyme-based melanogenesis inhibitory screening, and the mammalian cell-based assay appears to be a more reliable model for screening than the enzyme-based one.

Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

“…A pterocarpan (IC50 = 16.7 μM) and some isoflavones and isoflavans isolated from Dalbergia parviflora (Figure 11) have been also recently reported as inhibitors of the diphenolase activity of mushroom tyrosinase [95]. A series of flavonoids derivatives from the root bark of Broussonetia papyrifera, first of all broussoflavonol J (IC 50 = 9.29 µM), have been found to be more active than kojic acid as inhibitors of the monophenolase acitivty of the enzyme [92] (Figure 11).…”

“…Very potent (IC50 values in the range 0.10-7.5 μM) mushroom tyrosinase inhibitors have been isolated from licorice (Figure 12), the most active belonging to the isoflavan class [108][109][110]. A pterocarpan (IC 50 = 16.7 µM) and some isoflavones and isoflavans isolated from Dalbergia parviflora ( Figure 11) have been also recently reported as inhibitors of the diphenolase activity of mushroom tyrosinase [95].…”

“…At present, though a wide range of tyrosinase inhibitors from natural and synthetic sources have been reported, only a few of them, in addition to being effective, are known as safe compounds. No significant advances concerning toxicity issues of tyrosinase inhibitors seem to emerge from the literature survey carried out for this review, the relevant papers just reporting the results of in vitro cytotoxicity experiments [49,52,75,81,95,126,129,[131][132][133]136,137,147,163,[176][177][178]184,185,192,198,202,203,207,210,212,214,215,239,240,242,245] and only a few of in vivo experiments on zebrafish [130,206,209]. Therefore, it is essential to examine the efficacy and safety of inhibitors by checking e.g., whether or not the candidate inhibitor is substrate of tyrosinase being modified on exposure to the enzyme.…”

“…In the last five years, several natural and synthetic phenolic compounds have been described also as inhibitors of tyrosinase from animal and human sources. Most of these studies used B16 murine melanoma cell lines as a model [52,55,75,85,95,96,99,114,122,123,[127][128][129][132][133][134][135]138,139,151,153,155,163,, although some papers using zebrafish as an in vivo whole animal model have also been published [55,116,206]. As to the human sources, data on inhibition of human recombinant or purified tyrosinase [9,207], human melanoma cells [130,136], normal human melanocytes [208][209][210][211], or human skin models consisting of reconstructed three-dimensional human epidermis [212][213][214][215] have been published (Figure 21).…”

Optimization of Ultrasonic Flavonoid Extraction from Saussurea involucrate, and the Ability of Flavonoids to Block Melanin Deposition in Human Melanocytes

“…Arung et al [23] reported that a prenylated flavonoid from the wood of Artocarpus heterophyllus had good activity against melanin synthesis through a reduction in tyrosinase activity. Worrawat et al [24] isolated flavonoids from Dalbergia parviflora and showed that the flavonoids had inhibitory activity against murine tyrosinases and effectively inhibited melanin formation in B16 melanoma cells without being significantly toxic to the cells. These reports collectively suggest that SIFs extract could have good inhibitory activity against tyrosinase.…”