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Inhibition of melanogenesis by jineol from Scolopendra subspinipes mutilans via MAP-Kinase mediated MITF downregulation and the proteasomal degradation of tyrosinase

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ABSTRACT

In this study, the authors investigated the anti-melanogenic effects of 3,8-dihydroxyquinoline (jineol) isolated from Scolopendra subspinipes mutilans, the mechanisms responsible for its inhibition of melanogenesis in melan-a cells, and its antioxidant efficacy. Mushroom tyrosinase activities and melanin contents were determined in melan-a cells, and the protein and mRNA levels of MITF, tyrosinase, TYRP-1, and TYRP-2 were assessed. Jineol exhibited significant, concentration-dependent antioxidant effects as determined by DPPH, ABTS, CUPRAC, and FRAP assays. Jineol significantly inhibited mushroom tyrosinase activity by functioning as an uncompetitive inhibitor, and markedly inhibited melanin production and intracellular tyrosinase activity in melan-a cells. In addition, jineol abolished the expressions of tyrosinase, TYRP-1, TYRP-2, and MITF, thereby blocking melanin production and interfering with the phosphorylations of ERK1/2 and p38. Furthermore, specific inhibitors of ERK1/2 and p38 prevented melanogenesis inhibition by jineol, and the proteasome inhibitor (MG-132) prevented jineol-induced reductions in cellular tyrosinase levels. Taken together, jineol was found to stimulate MAP-kinase (ERK1/2 and p38) phosphorylation and the proteolytic degradation pathway, which led to the degradations of MITF and tyrosinase, and to suppress the productions of melanin.

No MeSH data available.


Antioxidant properties of jineol as determined by various in vitro antioxidant assays.DPPH radical scavenging activity (A), ABTS radical scavenging activity (B), CUPRAC activity (C), and FRAP activity (D) were analyzed as described in Materials and Methods. Each determination was made in triplicate, and results are represented as means ± SDs. *P < 0.05, **P < 0.01, versus non-treated controls by the Student’s t-test.
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f2: Antioxidant properties of jineol as determined by various in vitro antioxidant assays.DPPH radical scavenging activity (A), ABTS radical scavenging activity (B), CUPRAC activity (C), and FRAP activity (D) were analyzed as described in Materials and Methods. Each determination was made in triplicate, and results are represented as means ± SDs. *P < 0.05, **P < 0.01, versus non-treated controls by the Student’s t-test.

Mentions: Antioxidants protect cells from oxidative stress, and antioxidant capacity may be defined as the ability to scavenge free radicals and reactive oxygen and nitrogen species by hydrogen or electron donation. To determine whether jineol has radical scavenging activities, we examined its ability to scavenge DPPH- and ABTS-radicals. Jineol significantly scavenged DPPH· (a stable organic nitrogen radical) and ABTS•+, in a mixed electron and hydrogen atom transfer assay, in a dose-dependent manner (Fig. 2A and B). To confirm the electron-donating ability of jineol, we assessed its cupric-reducing antioxidant capacity (CUPRAC) and ferric-reducing antioxidant power (FRAP). Jineol was found to have strong reducing capacity and to act in a concentration-dependent manner (Fig. 2C and D), indicating it potently scavenges various free radicals by hydrogen atom transfer and electron donation. Pearson’s correlation analysis was performed to confirm its antioxidant and anti-melanogenic activities. Interestingly, the results obtained showed that antioxidant capacities of jineol ranked remarkable scores by exhibiting Pearson’s score as ρ = 0.989 for anti-tyrosinase activity, and ρ = 0.961 for anti-melanogenic activity (data not shown).


Inhibition of melanogenesis by jineol from Scolopendra subspinipes mutilans via MAP-Kinase mediated MITF downregulation and the proteasomal degradation of tyrosinase
Antioxidant properties of jineol as determined by various in vitro antioxidant assays.DPPH radical scavenging activity (A), ABTS radical scavenging activity (B), CUPRAC activity (C), and FRAP activity (D) were analyzed as described in Materials and Methods. Each determination was made in triplicate, and results are represented as means ± SDs. *P < 0.05, **P < 0.01, versus non-treated controls by the Student’s t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5385534&req=5

f2: Antioxidant properties of jineol as determined by various in vitro antioxidant assays.DPPH radical scavenging activity (A), ABTS radical scavenging activity (B), CUPRAC activity (C), and FRAP activity (D) were analyzed as described in Materials and Methods. Each determination was made in triplicate, and results are represented as means ± SDs. *P < 0.05, **P < 0.01, versus non-treated controls by the Student’s t-test.
Mentions: Antioxidants protect cells from oxidative stress, and antioxidant capacity may be defined as the ability to scavenge free radicals and reactive oxygen and nitrogen species by hydrogen or electron donation. To determine whether jineol has radical scavenging activities, we examined its ability to scavenge DPPH- and ABTS-radicals. Jineol significantly scavenged DPPH· (a stable organic nitrogen radical) and ABTS•+, in a mixed electron and hydrogen atom transfer assay, in a dose-dependent manner (Fig. 2A and B). To confirm the electron-donating ability of jineol, we assessed its cupric-reducing antioxidant capacity (CUPRAC) and ferric-reducing antioxidant power (FRAP). Jineol was found to have strong reducing capacity and to act in a concentration-dependent manner (Fig. 2C and D), indicating it potently scavenges various free radicals by hydrogen atom transfer and electron donation. Pearson’s correlation analysis was performed to confirm its antioxidant and anti-melanogenic activities. Interestingly, the results obtained showed that antioxidant capacities of jineol ranked remarkable scores by exhibiting Pearson’s score as ρ = 0.989 for anti-tyrosinase activity, and ρ = 0.961 for anti-melanogenic activity (data not shown).

View Article: PubMed Central - PubMed

ABSTRACT

In this study, the authors investigated the anti-melanogenic effects of 3,8-dihydroxyquinoline (jineol) isolated from Scolopendra subspinipes mutilans, the mechanisms responsible for its inhibition of melanogenesis in melan-a cells, and its antioxidant efficacy. Mushroom tyrosinase activities and melanin contents were determined in melan-a cells, and the protein and mRNA levels of MITF, tyrosinase, TYRP-1, and TYRP-2 were assessed. Jineol exhibited significant, concentration-dependent antioxidant effects as determined by DPPH, ABTS, CUPRAC, and FRAP assays. Jineol significantly inhibited mushroom tyrosinase activity by functioning as an uncompetitive inhibitor, and markedly inhibited melanin production and intracellular tyrosinase activity in melan-a cells. In addition, jineol abolished the expressions of tyrosinase, TYRP-1, TYRP-2, and MITF, thereby blocking melanin production and interfering with the phosphorylations of ERK1/2 and p38. Furthermore, specific inhibitors of ERK1/2 and p38 prevented melanogenesis inhibition by jineol, and the proteasome inhibitor (MG-132) prevented jineol-induced reductions in cellular tyrosinase levels. Taken together, jineol was found to stimulate MAP-kinase (ERK1/2 and p38) phosphorylation and the proteolytic degradation pathway, which led to the degradations of MITF and tyrosinase, and to suppress the productions of melanin.

No MeSH data available.