Abstract
Hyperpigmentation diseases of the skin require topical treatment with depigmenting agents. We investigated the hypopigmented mechanisms of sargahydroquinoic acid (SHQA) in alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells. SHQA reduced cellular tyrosinase (TYR) activity and melanin content in a concentration-dependent manner and attenuated the expression of TYR and tyrosinase-related protein 1 (TRP1), along with their transcriptional regulator, microphthalmia-associated transcription factor (MITF). SHQA also suppressed α-MSH-induced cellular production of cyclic adenosine monophosphate (cAMP), which inhibited protein kinase A (PKA)-dependent cAMP-responsive element-binding protein (CREB) activation. Docking simulation data showed a potential binding affinity of SHQA to the regulatory subunit RIIβ of PKA, which may also adversely affect PKA and CREB activation. Moreover, SHQA activated ERK1/2 signaling in B16F10 cells, stimulating the proteasomal degradation of MITF. These data suggest that SHQA ameliorated hyperpigmentation in α-MSH-stimulated B16F10 cells by downregulating MITF via PKA inactivation and ERK1/2 phosphorylation, indicating that SHQA is a potent therapeutic agent against skin hyperpigmentation disorders.
Highlights
Skin pigmentation is a physiological process in which melanin pigments are synthesized in epidermal melanocytes, matured, and transferred to the neighboring keratinocytes
Carcinogenic potential [12] and allergic contact dermatitis [13] caused by kojic acid, and hyperpigmentation by higher concentrations of arbutin [14] have been reported in previous studies
Because cyclic adenosine monophosphate (cAMP) plays a pivotal role in melanogenic signaling pathways, we examined whether sargahydroquinoic acid (SHQA) influences the cellular level of cAMP
Summary
Skin pigmentation is a physiological process in which melanin pigments are synthesized in epidermal melanocytes, matured, and transferred to the neighboring keratinocytes. Melanin synthesis is catalyzed by tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and TRP2. Hyperpigmentation occurs due to either increased numbers of melanocytes or melanogenic enzymes [4,5] It is associated with several skin diseases such as melasma, freckles, moles, and lentigo [6,7]. Carcinogenic potential [12] and allergic contact dermatitis [13] caused by kojic acid, and hyperpigmentation by higher concentrations of arbutin [14] have been reported in previous studies. In response to alpha-melanocyte-stimulating hormone (α-MSH) or other cAMP stimulators, increased production of cellular cAMP leads to the activation of protein kinase A (PKA) via dissociating catalytic subunits from a regulatory subunit dimer. We investigated the hypopigmented mechanisms of SHQA in α-MSH-stimulated B16F10 mouse melanoma cells
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