Ethanolic extract of Melia azedarach L. induces melanogenesis through the cAMP-PKA-CREB signaling pathway

Kim, Miok; Park, Se Jin; Park, See‐Hyoung; Oh, Sae Woong; Lee, Seung Eun; Yoo, Ju Ah; Kwon, Ki-Won; Kim, Jangsoon; Kim, Min Hee; Cho, Jae Youl; Lee, Jongsung

doi:10.1007/s13273-019-0009-9

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…However, in this study, TSA reduced PKA/CREB signaling and not MAPK signaling, implying a different mode of action due to a different chemical structure. The ethanolic extract of Melia azedarach L. solely affects the cAMP/PKA/CREB pathway in melanogenesis, while resorcinol from argan oil has an anti-melanogenic effect by suppressing cAMP signaling instead of MAPKs [ 41 , 47 ], implying that structurally similar compounds could be included in these extracts. Hence, natural substances seem to have diverse regulatory mechanisms that affect melanogenesis based on their structural features.…”

Section: Discussionmentioning

confidence: 99%

Antimelanogenesis Effects of Theasinensin A

Lim

Kim

Park

et al. 2021

IJMS

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Theasinensin A (TSA) is a major group of catechin dimers mainly found in oolong tea and black tea. This compound is also manufactured with epigallocatechin gallate (EGCG) as a substrate and is refined after the enzyme reaction. In previous studies, TSA has been reported to be effective against inflammation. However, the effect of these substances on skin melanin formation remains unknown. In this study, we unraveled the role of TSA in melanogenesis using mouse melanoma B16F10 cells and normal human epidermal melanocytes (NHEMs) through reverse transcription polymerase chain reaction (RT-PCR), Western blotting analysis, luciferase reporter assay, and enzyme-linked immunosorbent assay analysis. TSA inhibited melanin formation and secretion in α-melanocyte stimulating hormone (α-MSH)-induced B16F10 cells and NHEMs. TSA down-regulated the mRNA expression of tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1), and Tyrp2, which are all related to melanin formation in these cells. TSA was able to suppress the activities of certain proteins in the melanocortin 1 receptor (MC1R) signaling pathway associated with melanin synthesis in B16F10 cells: cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), protein kinase A (PKA), tyrosinase, and microphthalmia-associated transcription factor (MITF). We also confirmed α-MSH-mediated CREB activities through a luciferase reporter assay, and that the quantities of cAMP were reduced by TSA in the enzyme linked immunosorbent assay (ELISA) results. Based on these findings, TSA should be considered an effective inhibitor of hyperpigmentation.

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Section: Discussionmentioning

confidence: 99%

Antimelanogenesis Effects of Theasinensin A

Lim

Kim

Park

et al. 2021

IJMS

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“…PKA entails phosphorylation at Ser133 of cAMP-response element binding protein (CREB) and subsequent activation of MITF expression. The extracts that up-regulate pigment formation are Melia azedarach bark [ 99 ] and Dalbergia odorifera fruit [ 100 ]. In B16 melanoma cells, they increase the intracellular cAMP level and PKA activity, translating to increased phosphorylation of CREB, its downstream signaling protein, followed by up-regulation of MITF and TYR expression.…”

Section: Mechanisms Of Melanogenesis-related Signaling Pathway Modula...mentioning

confidence: 99%

The Modulation of Melanogenesis in B16 Cells Upon Treatment with Plant Extracts and Isolated Plant Compounds

et al. 2022

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Plants are a rich source of secondary metabolites that exhibit numerous desired properties. The compounds may influence the biology of melanocytes, pigment cells that produce melanin, by modulating numerous signaling pathways, including cAMP/PKA, MAPKs and PI3K/AKT. Its downstream target is microphthalmia-associated transcription factor, responsible for the expression of the tyrosinase enzyme, which plays a major role in melanogenesis. Therefore, this literature review aims to provide insights related to melanogenesis modulation mechanisms of plant extracts and isolated plant compounds in B16 cells. Database searches were conducted using online-based library search instruments from 2012 to 2022, such as NCBI-PubMed and Google Scholar. Upregulation or downregulation of signaling pathways by phytochemicals can influence skin hypo- and hyperpigmentation by changing the level of melanin production, which may pose a significant cosmetic issue. Therefore, plant extracts or isolated plant compounds may be used in the therapy of pigmentation disorders.

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“…The induction of cAMP production induces the activation of PKA, which phosphorylates the cAMP response element-binding protein (CREB) and CREB-binding protein and consequently upregulates the expression of key melanogenic genes, including MITF, TRY, TRP1, and TRP 2. 24 Therefore, we investigated whether chrysoeriol influences the cAMP-PKA signaling pathway in B16F10 cells. Western blotting was performed to confirm the effect of chrysoeriol on PKA phosphorylation.…”

Section: Chrysoeriol Stimulates the Pka Signaling Pathways In B16f10 ...mentioning

confidence: 99%

Chrysoeriol Enhances Melanogenesis in B16F10 Cells Through the Modulation of the MAPK, AKT, PKA, and Wnt/β-Catenin Signaling Pathways

Hyun

2022

Natural Product Communications

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Chrysoeriol is a 3′-O-methoxy flavone, chemically a derivative of luteolin, which is commonly found across the plant kingdom. Chrysoeriol is of great scientific interest because of its promising anti-inflammatory, anti-cancer, antioxidative, anti-lipase, anti-xanthin oxidase, and antimicrobial activities against multidrug-resistant (MDR) bacterial pathogens; however, its effects on melanogenesis have not yet been elucidated. Here, we report a novel effect of chrysoeriol on melanogenesis in B16F10 cells. Chrysoeriol treatment significantly increased the expression of the melanogenic enzymes tyrosinase (TRY), tyrosinase-related protein-1 (TRP-1), and TRP-2 and upregulated the expression of microphthalmia-associated transcription factor (MITF) in a concentration-dependent manner. Furthermore, chrysoeriol suppressed the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) in a concentration-dependent manner. In addition, chrysoeriol treatment increased the phosphorylation of p38 mitogen-activated protein kinase (MAPK), glycogen synthase kinase (GSK)-3β, β-catenin, and protein kinase A (PKA) and decreased the production of β-catenin, which is involved in the transcriptional activation of MITF in melanogenesis. Finally, the structure–activity relationship (SAR) of chrysoeriol and its derivatives, including luteolin and apigenin, with regard to their melanin inhibitory activity was also investigated; we identified the significance of the 4′-OH group and C-3′ methoxylation in melanogenesis. Together, these findings indicate that chrysoeriol promotes melanogenesis in B16F10 cells by upregulating the expression of melanogenic enzymes through the MAPK, phosphatidylinositol 3-kinase (PI3K)/AKT, PKA, and Wnt/β-catenin signaling pathways; thus, chrysoeriol may be used as a cosmetic ingredient to promote melanogenesis or as a therapeutic agent against hypopigmentation disorders.

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Ethanolic extract of Melia azedarach L. induces melanogenesis through the cAMP-PKA-CREB signaling pathway

Cited by 5 publications

References 23 publications

Antimelanogenesis Effects of Theasinensin A

Antimelanogenesis Effects of Theasinensin A

The Modulation of Melanogenesis in B16 Cells Upon Treatment with Plant Extracts and Isolated Plant Compounds

Chrysoeriol Enhances Melanogenesis in B16F10 Cells Through the Modulation of the MAPK, AKT, PKA, and Wnt/β-Catenin Signaling Pathways

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