Daphnetin inhibits α-MSH-induced melanogenesis via PKA and ERK signaling pathways in B16F10 melanoma cells

Nam, Garam; An, Sung Kwan; Park, In-Chul; Bae, Seunghee; Lee, Jae Ho

doi:10.1093/bbb/zbac016

Cited by 16 publications

(11 citation statements)

References 72 publications

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“…Mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK), are deeply involved in melanogenesis. In particular, ERK, through its phosphorylation, is responsible for regulating MITF protein stability, i.e., the phosphorylation of MITF decreases its stability and leads to its degradation in proteasomes, and ERK dephosphorylation paradoxically interrupts MITF degradation, thereby activating melanogenesis [ 35 , 36 , 37 ]. Therefore, we next sought to examine whether imperatorin regulates MITF activity via a MAPK pathway.…”

Section: Resultsmentioning

confidence: 99%

“…The activation of ERK is associated with a reduction in MITF degradation and pigmentation, while the inhibition of ERK increases melanin synthesis. Thus, MAPK signals in melanocytes are promising targets for the development of cosmetics and treatments for skin pigmentation through which MITF expression and stability can be increased [ 35 , 36 , 37 ]. Therefore, we evaluated the effectiveness of imperatorin for the inhibition of the ERK signaling pathway to further explore the molecular mechanisms of melanin synthesis in B16F10 cells.…”

Section: Discussionmentioning

confidence: 99%

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Imperatorin Positively Regulates Melanogenesis through Signaling Pathways Involving PKA/CREB, ERK, AKT, and GSK3β/β-Catenin

Kim

Hyun

2022

Molecules

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The present study investigated the melanogenic effects of imperatorin and isoimperatorin and the underlying mechanisms of imperatorin using a mouse melanoma B16F10 model. Interestingly, treatment with 25 μM of either imperatorin or isoimperatorin, despite their structural differences, did not produce differences in melanin content and intracellular tyrosinase activity. Imperatorin also activated the expression of melanogenic enzymes, such as tyrosinase (TYR) and tyrosinase-related proteins TYRP-1 and TYRP-2. Mechanistically, imperatorin increases melanin synthesis through the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA)/cAMP-responsive element-binding protein (CREB)-dependent upregulation of microphthalmia-associated transcription factor (MITF), which is a key transcription factor in melanogenesis. Furthermore, imperatorin exerted melanogenic effects by downregulating extracellular signal-regulated kinase (ERK) and upregulating phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/glycogen synthesis kinase-3β (GSK-3β). Moreover, imperatorin increased the content of β-catenin in the cell cytoplasm and nucleus by reducing the content of phosphorylated β-catenin (p-β-catenin). Finally, we tested the potential of imperatorin in topical application through primary human skin irritation tests. These tests were performed on the normal skin (upper back) of 31 volunteers to determine whether 25 or 50 µM of imperatorin had irritation or sensitization potential. During these tests, imperatorin did not induce any adverse reactions. Taken together, these findings suggest that the regulation of melanogenesis by imperatorin can be mediated by signaling pathways involving PKA/CREB, ERK, AKT, and GSK3β/β-catenin and that imperatorin could prevent the pathogenesis of pigmentation diseases when used as a topical agent.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Imperatorin Positively Regulates Melanogenesis through Signaling Pathways Involving PKA/CREB, ERK, AKT, and GSK3β/β-Catenin

Kim

Hyun

2022

Molecules

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“…In this investigation, daphnetin, one of the constituents of Daphne odora , accounted for 0.047% of DOE, and effectively inhibited in vitro tyrosinase activity. Recently, the anti-melanogenic effect of daphnetin was exerted by the regulation of the PKA/CREB and the ERK/MSK1/CREB pathways [ 27 ]. Daphnetin has been known to possess notable therapeutic properties against malaria, allergy, inflammatory disorders, and malignant tumors [ 28 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Daphne odora Exerts Depigmenting Effects via Inhibiting CREB/MITF and Activating AKT/ERK-Signaling Pathways

Eom

Jeong

Ryu

et al. 2022

CIMB

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Daphne odora, a blooming shrub, has been traditionally used for various medicinal purposes. However, information on its anti-melanogenic activity and dermal application is limited. In this study, the Daphne odora extract (DOE), with constituents including daphnetin, was used to investigate depigmenting activity and the underlying mechanism of Daphne odora. DOE inhibited in vitro and cellular tyrosinase activity in a dose-dependent manner, and reduced the α-MSH-induced melanin biosynthesis to a control level. The protein expressions of melanin synthesis-related enzymes were also significantly reduced by DOE. Moreover, DOE decreased the phosphorylation of cAMP-response element binding proteins (CREBs) induced by α-MSH in B16F10 cells, while it activated phosphorylated extra-cellular signal-regulated kinases (ERKs) and protein kinase B (AKT) expression. These results suggest that DOE might inhibit the melanogenesis signaling pathways by activating ERK- and AKT-signaling pathways to regulate the expression of CREB and MITF and its downstream pathways. Therefore, DOE could potentially be developed as a depigmenting agent.

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“…DAP downregulated the phosphorylation of kinases such as PKA, ERK, mitogen and stress activated protein kinase (MSK)-1 and cAMP response element binding protein (CREB). It inhibited the melanin synthesis, and exhibited the anti-pigmentation activity by modulating PKA/CREB, and ERK/MSK1/CREB pathways ( Nam et al, 2022 ).…”

Section: Pharmacological Activities Of Daphnetinmentioning

confidence: 99%

Daphnetin: A bioactive natural coumarin with diverse therapeutic potentials

et al. 2022

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Daphnetin (DAP), a coumarin derivative extracted from Daphne species, is biologically active phytochemical with copious bioactivities including anti-inflammatory, anti-oxidant, neuroprotective, analgesic, anti-pyretic, anti-malarial, anti-bacterial, anti-arthritic, neuroprotective, hepatoprotective, nephroprotective, and anti-cancer activities. A wide range of studies have been conducted exploring the significance and therapeutic potential of DAP. This study reviewed various databases such as NCBI, PubMed, Web of Science, Scopus and Google Scholar for published research articles regarding the sources, synthesis, and various bioactivities of DAP using different key words, including but not limited to “pharmacological activities,” “sources,” “neuroprotective effect,” “synthesis,” “cancer,” “anti-inflammatory effect” of “daphnetin.” Furthermore, this review encompasses both in-vivo and in-vitro studies on DAP for treating various diseases. A comprehensive review of the literature revealed that the DAP had a promising pharmacological and safety profile, and could be employed as a pharmaceutical moiety to treat a variety of illnesses including microbial infections, cancer, arthritis, hepatic damage, inflammation and neurological anomalies. The current review intends to provide an in-depth focus on all pharmacological activities and therapeutic approaches for the pharmaceutical and biomedical researchers.

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Daphnetin inhibits α-MSH-induced melanogenesis via PKA and ERK signaling pathways in B16F10 melanoma cells

Cited by 16 publications

References 72 publications

Imperatorin Positively Regulates Melanogenesis through Signaling Pathways Involving PKA/CREB, ERK, AKT, and GSK3β/β-Catenin

Imperatorin Positively Regulates Melanogenesis through Signaling Pathways Involving PKA/CREB, ERK, AKT, and GSK3β/β-Catenin

Daphne odora Exerts Depigmenting Effects via Inhibiting CREB/MITF and Activating AKT/ERK-Signaling Pathways

Daphnetin: A bioactive natural coumarin with diverse therapeutic potentials

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