Melanogenic Effects of Maclurin Are Mediated through the Activation of cAMP/PKA/CREB and p38 MAPK/CREB Signaling Pathways

Abstract

Melanogenesis is the biological process which the skin pigment melanin is synthesized to protect the skin against ultraviolet irradiation and other external stresses. Abnormal biology of melanocytes is closely associated with depigmented skin disorders such as vitiligo. In this study, we examined the effects of maclurin on melanogenesis and cytoprotection. Maclurin enhanced cellular tyrosinase activity as well as cellular melanin levels. We found that maclurin treatment increased the expression of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein- (TRP-) 1, TRP-2, and tyrosinase. Mechanistically, maclurin promoted melanogenesis through cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein-dependent upregulation of MITF. CREB activation was found to be mediated by p38 mitogen-activated protein kinase (MAPK) or cAMP-protein kinase A (PKA) signaling. In addition, maclurin-induced CREB phosphorylation was mediated through the activation of both the cAMP/PKA and the p38 MAPK signaling pathways. Maclurin-induced suppression of p44/42 MAPK activation also contributed to its melanogenic activity. Furthermore, maclurin showed protective effects against H2O2 treatment and UVB irradiation in human melanocytes. These findings indicate that the melanogenic effects of maclurin depend on increased MITF gene expression, which is mediated by the activation of both p38 MAPK/CREB and cAMP/PKA/CREB signaling. Our results thus suggest that maclurin could be useful as a protective agent against hypopigmented skin disorders.

Anti-Melanogenesis Activity of 6-O-Isobutyrylbritannilactone from Inula britannica on B16F10 Melanocytes and In Vivo Zebrafish Models

“…This transition factor is regulated by mitogen-activated protein kinase (MAPK) signaling pathways, such as the ERK pathway, which also subsequently results in increased tyrosinase expression [ 38 , 39 ]. ERK activation signals increase phosphorylated CREB and consequent MITF expression [ 40 , 41 , 42 ]. Thus, we investigated the ways in which IBL affected the phosphorylation of Akt and ERK.…”

Anti-Melanogenesis Effects of Lotus Seedpod In Vitro and In Vivo

“…Consistent with this is the demonstration by Bellei et al, showing a similar response of B16F0 and normal human melanocytes to promote melanogenesis when stimulating with various GSK3β-specific inhibitors [ 33 ]. Hwang et al used the human epidermal melanocytes to explore the possible mechanism of maclurin, a natural xanthone, on melanin synthesis inhibition, including p38- and PKA-mediated signaling [ 34 ]. As the present study was a preliminary one to investigate the effects of LSE on melanogenesis, the effect of the extract upon normal melanocytes and UV irradiation on epidermal melanocytes separated from the dermis would be interesting to validate the photoprotective mechanism and thereby, needs to be explored in the future.…”

Cryptosporidial Infection Suppresses Intestinal Epithelial Cell MAPK Signaling Impairing Host Anti-Parasitic Defense

“…Infected IEC4.1 cells demonstrated a significant alteration in gene expression profile (GEO database: GSE112247) [ 24 ]. Intriguingly, expression levels of MAPK-controlled genes, such as Mef2a / C / D , Znhit1 , Bmi-1 , Usf1 , Creb , Pla2 , and Mnk1 / 2 [ 27 , 28 , 29 , 30 , 31 , 32 , 33 ], were generally either not changed or decreased in infected cells, with a 24.6% to 54.1% decrease compared to that in the non-infected control cells ( Figure 1 A).Consistent with results from previous studies [ 9 , 15 , 23 , 24 ], many other inflammatory genes not directly related to the MAPK signaling were upregulated in the infected cells, such as Ifnb1 , IL20 , Ligp1 , Ido2 , and Celf1 ( Figure 1 A). Therefore, we speculated that C. parvum infection may suppress p38/MAPK signaling activity in infected intestinal epithelial cells.…”