Table I.
Bioactive, naturally occurring compounds and their respective mechanism of action on tyrosinase and MITF expression.
| Structure type | Source | Mechanism of action | (Refs.) |
|---|---|---|---|
| Phenolic compounds | |||
| 2-[4-(3-Hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol | Juglans mandshurica | ERK-associated pathway resulting in the downregulation of MITF | (34) |
| Protocatechuic acid | Pear fruits | Downregulation of the cAMP/CREB signaling pathway | (49) |
| Ethyl acetate fraction of Oroxylum indicum Vent. seeds | Oroxylum indicum | Activation p38, ERK1/2 and JNK phosphorylation and suppression of MITF expression | (47) |
| Hispolon | Phellinus linteus | Downregulation of MITF and activation of caspase-3, -8 and -9 | (51) |
| Heracleum moellendorffii Hance extract | Heracleum moellendorffii | Activation of ERK1/2 and subsequent degradation of MITF | (46) |
| [6]-Shogaol | Ginger rhizome | Acceleration of ERK and PI3K/Akt-mediated MITF degradation | (45) |
| Sesamol | Sesame | Regulation of melanin-related signal transduction | (48) |
| Phenolic extracts | Rape bee pollen | Inhibition of the cAMP/MITF/TYR pathway | (50) |
| Flavonoids | |||
| Isoorientin | Gentiana veitchiorum Hemsl. flowers | Suppression of MITF through CREB | (52) |
| Hesperidin | Rutaceae citrus species | Activation of ERK1/2 and downregulation of MITF | (56) |
| Gallic acid | Gallnut, lacquer tree, tea | Inhibition of PI3K/AKT, MEK/ERK and Wnt/β-Catenin signaling to downregulate MITF | (58) |
| Ethyl acetate fraction of bamboo stems | Phyllostachys nigra f. henosis | PKA/CREB-mediated MITF downregulation | (53) |
| Kaempferol-7-O-D-glucuronide (K7G) and tilianin | Cryptotaenia japonica | CREB- and MAPK-associated signaling pathways | (54) |
| Flavonoids and polyphenolic compounds | |||
| Pomegranate concentrate powder | Pomegranates | Inactivation of p38 and PKA signaling pathways to reduce the phosphorylation of CREB and MITF | (55) |
| Sorghum ethanolic extract | Sorghum | Suppression of PAX3-mediated MITF gene promoter activity | (59) |
| Terpenoids | |||
| Zerumbone | Zingiber officinale | Increased phosphorylation of ERK1/2 to downregulate MITF | (69) |
| Ganodermanondiol | Ganoderma lucidum | Inhibition of the MAPK cascade and cAMP-dependent signal pathway | (68) |
| N-hexane fraction rich in methyl linoleate and methyl linolenate | Sageretia thea | Suppression of the AKT/GSK3β signaling pathway | (61) |
| Hinokitiol | Cupressaceous plants | Inhibition of the AKT/mTOR signaling pathway | (60) |
| Ginsenoside Rg3 | Panax ginseng | Activation of ERK to downregulate MITF | (62) |
| Polysaccharides | |||
| Ganoderma lucidum polysaccharide | Ganoderma lucidum | Inhibition of cAMP/PKA and ROS/MAPK signaling pathways | (65) |
| S. japonicus extracts | Stichopus japonicus | Inhibition of ERK activation and reduction of the expression of MITF | (66) |
| Alkaloids | |||
| Betaine | Crustaceans, beetroot | Inhibition of cAMP/PKA/CREB signaling and activation of AKT-GSK3β signaling, leading to the degradation of MITF | (63) |
| Lignanoids | |||
| Gomisin N | Schisandra chinensis | Inactivation of the PI3K/AKT and MAPK/ERK signaling pathways | (57) |
| Quinolines | |||
| 3,8-Dihydroxyquinoline (jineol) | Scolopendra subspinipes mutilans | Activation of ERK1/2 and p38 MAPK signaling, leading to the proteolytic degradation of MITF | (64) |
| Fatty acids | |||
| Linoleic acid and oleic acid | Spent coffee grounds | Downregulation of cAMP/PKA, PI3K/AKT and MAPK signaling pathways | (67) |
cAMP, cyclic AMP; GSK-3β, glycogen synthase kinase-3β; PKA, protein kinase A; MITF, microphthalmia-associated transcription factor; CREB, cAMP response element binding protein; GSK-3β, glycogen synthase kinase-3β.