Upregulation of Melanogenesis and Tyrosinase Activity: Potential Agents for Vitiligo

Abstract

Melanin, the compound primarily responsible in humans for hair, eye and skin pigmentation, is produced by melanocytes through a complicated process called melanogenesis that is catalyzed by tyrosinase and other tyrosinase-related proteins. The abnormal loss of melanin causes dermatological problems such as vitiligo. Hence the regulation of melanogenesis and tyrosinase activity is very important for treating hypopigmentary disorders. Many melanogenesis stimulators have been discovered during the past decade. This article reviews recent advances in research on extracts and active ingredients of plants, synthesized compounds with stimulating effect on melanin synthesis and tyrosinase activity, as well as their influence on the expression of related proteins and possible signaling pathways for the design and development of novel anti-vitiligo agents.

Keywords: analogues; melanogenesis; natural products; plant extracts; synthesized derivatives; tyrosinase activity; vitiligo.

Figure 1

Vitiligo with typical lesions of the face and trunk [3].

Figure 2

Regulation of melanogenesis through different signaling pathways [18,19].

Scheme 1

Melanogenesis catalyzed by tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2 (TRP-2).

Figure 3

Structures of compounds isolated from Vernonia anthelmintica [47,48].

Figure 4

Structures of flavanones isolated from Citrus.

Figure 5

Model of signalling pathways involved in naringenin-induced melanogenesis [55].

Scheme 2

Synthesis of novel fluorescent flavanone-BODIPY probe 7 [57].

Figure 6

Structures of isosakuranetin and sakuranetin.

Figure 7

Structures of chalcone derivatives and analogues with activator effect on tyrosinase [68,69].

Figure 8

Structures of the benzothiazole and amide chalcones.

Figure 9

Structures of the chalcones derivatives bearing1,2,3-triazole moieties.

Figure 10

Structures of the chalcones derivatives bearing isoxazole moieties.

Figure 11

Structures of the chalcones with activator effect and SAR.

Figure 12

Structures of the compounds isolated from Helminthostachys zeylanica.

Figure 13

Structures of the synthesized quercetin glycosides.

Figure 14

Structures of the synthesized quercetin derivatives.

Figure 15

Structures of three compounds with activator effect on tyrosinase.

Figure 16

Structures of polymethoxylated flavones.

Figure 17

Structures of the4′-O-methylated and corresponding 4′-OH flavonoids.

Figure 18

Structure of puerarin.

Figure 19

Structures of coumarins isolated from seven Umbelliferae crude drugs.

Figure 20

Structures of valproic acid and 5,7-dimethoxycoumarin.

Figure 21

Structures of the coumarin derivatives bearing isoxazole moieties.

Figure 22

Structures of the synthesized furocoumarin derivatives.

Figure 23

Structure of glycyrrhizin isolated from Glycyrrhiza glabra L.

Figure 24

Structure of geniposide isolated from Gardenia jasminoides Ellis fruits.

Figure 25

Structure of lupenone isolated from leaf effects extracts of Erica multiflora.

Figure 26

Structure of triterpene glycosides isolated from aerial parts of Weigela subsessilis.

Figure 27

Structure of triterpenoids and phenolic compound isolated from fruiting bodies of Inonotus hispidus.

Figure 28

Structure of THSG isolated from dried tuber root of Polygonum multiflorum.

Figure 29

Structures of dihydroresveratrol glucosides.

Figure 30

Structure of the synthetic aurones.

Figure 31

Structure of rosmarinic acid.

Figure 32

Structure of epigallocatechin-3-gallate.

Figure 33

Structure of kavalactones and glucosylsterols isolated from the rhizome extract of Piper methysticum.

Figure 34

Structure of (−)-cubebin.

Figure 35

A proposed scheme showing the activation mechanism of cubebin on melanogenesis [107].

Figure 36

Structure of PIP and three analogues.

Figure 37

Structure of JAK inhibitors.