scholarly journals Ethanolic Extract of Hippocampus abdominalis Exerts Anti-Melanogenic Effects in B16F10 Melanoma Cells and Zebrafish Larvae by Activating the ERK Signaling Pathway

Cosmetics ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 1 ◽  
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Yung Hyun Choi ◽  
Seungheon Lee ◽  
Jiwon Sung ◽  
Cho Rong Lee ◽  
...  
Keyword(s):  
Heart Rate ◽  
Signaling Pathway ◽  
Ethanolic Extract ◽  
Adenosine Monophosphate ◽  
Melanoma Cells ◽  
Erk Signaling ◽  
B16f10 Melanoma ◽  
Zebrafish Larvae ◽  
B16f10 Melanoma Cells ◽  
Hippocampus Abdominalis

The big belly seahorse (Hippocampus abdominalis), a well-known ingredient of traditional medicine, possesses anti-inflammatory, anti-aging, anti-fatigue, and anti-thrombotic properties, and also increases male fertility. This study demonstrates that the ethanolic extract of dried H. abdominalis (EEHA) has anti-melanogenic effects in B16F10 melanoma cells and zebrafish larvae. EEHA significantly reduced the α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis in B16F10 melanoma cells without causing cytotoxicity. At a concentration of 200 µg/mL, EEHA had significant anti-melanogenic activity in zebrafish larvae, accompanied by a severe reduction in the heart rate (118 ± 17 heartbeats/min) compared to that of the untreated group (185 ± 8 heartbeats/min), indicating that EEHA induces cardiotoxicity at high concentrations. Below 100 µg/mL, EEHA significantly reduced melanogenesis in zebrafish larvae in the presence or absence of α-MSH, while the heart rate remained unaltered. Additionally, EEHA downregulated the release of cyclic adenosine monophosphate (cAMP) and the phosphorylation of cAMP response element-binding protein (CREB) in B16F10 melanoma cells, which inhibited microphthalmia-associated transcription factor (MITF), leading to the inhibition of tyrosinase activity. EEHA also increased the phosphorylation of extracellular-signal regulated kinase (ERK). The ERK inhibitor PD98059 interfered with the anti-melanogenic activity of EEHA in B16F10 melanoma cells and zebrafish larvae, indicating that the ERK signaling pathway might regulate the anti-melanogenic properties of EEHA. Altogether, we conclude that EEHA represses the cAMP–CREB–MITF axis, which consequently inhibits tyrosinase-mediated melanogenesis. We propose that at low concentrations, EEHA can serve as a promising anti-melanogenic agent that could be used to prepare whitening cosmetics and for treating melanogenic disorders.

New Synthesized Galloyl‐RGD Inhibits Melanogenesis by Regulating the CREB and ERK Signaling Pathway in B16F10 Melanoma Cells

2020 ◽  
Vol 96 (6) ◽  
pp. 1321-1331
Author(s):  
Seo Yeon Shin ◽  
Sang Ouk Sun ◽  
Jae Yeon Ko ◽  
Yun Seo Oh ◽  
Seung‐Sik Cho ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Melanoma Cells ◽  
Erk Signaling ◽  
B16f10 Melanoma ◽  
B16f10 Melanoma Cells

scholarly journals Flavonoid Glycosides from Ziziphus jujuba var. inermis (Bunge) Rehder Seeds Inhibit α-Melanocyte-Stimulating Hormone-Mediated Melanogenesis

2021 ◽  
Vol 22 (14) ◽  
pp. 7701
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Kyoung-Tae Lee ◽  
Athapaththu Mudiyanselage Gihan Kavinda Athapaththu ◽  
Yung-Hyun Choi ◽  
Jaeyoung Hwang ◽  
...  
Keyword(s):  
Biological Activities ◽  
Melanoma Cells ◽  
Flavonoid Glycosides ◽  
B16f10 Melanoma ◽  
Anticancer Activities ◽  
Melanocyte Stimulating Hormone ◽  
Zebrafish Larvae ◽  
B16f10 Melanoma Cells ◽  
Ziziphus Jujuba ◽  
Stimulating Hormone

Ziziphus jujuba extracts possess a broad spectrum of biological activities, such as antioxidant and anticancer activities in melanoma cancers. Nevertheless, the compounds contain high antioxidant capacities and anticancer activities in melanoma cells, shown to be effective in hyperpigmentation disorders, but whether flavonoid glycosides from Z. jujuba regulate anti-melanogenesis remains unclear. In this study, we evaluated the anti-melanogenic activity of five flavonoid glycosides from Z. jujuba var. inermis (Bunge) Rehder seeds, including jujuboside A (JUA), jujuboside B (JUB), epiceanothic acid (EPA), betulin (BTL), and 6’’’-feruloylspinosin (FRS), in B16F10 melanoma cells and zebrafish larvae. According to our results, JUB, EPA, and FRS potently inhibited α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis and prevented hyperpigmentation in zebrafish larvae. In particular, under α-MSH-stimulated conditions, FRS most significantly inhibited α-MSH-induced intracellular and extracellular melanin content in B16F10 melanoma cells. Additionally, JUB, EPS, and FRS remarkably downregulated melanogenesis in α-MSH-treated zebrafish larvae, with no significant change in heart rate. Neither JUA nor BTA were effective in downregulating melanogenesis in B16F10 melanoma cells and zebrafish larvae. Furthermore, JUB, EPA, and FRS directly inhibited in vitro mushroom tyrosinase enzyme activity. JUB, EPA, and FRS also downregulated cyclic adenosine monophosphate (cAMP) levels and the phosphorylation of cAMP-response element-binding protein (CREB), and subsequent microphthalmia transcription factor (MITF) and tyrosinase expression. In conclusion, this study demonstrated that JUB, EPA, and FRS isolated from Z. jujuba var. inermis (Bunge) Rehder seeds exhibit potent anti-melanogenic properties by inhibition of the cAMP-CERB-MITF axis and consequent tyrosinase activity.

scholarly journals Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABAA and GABAB Receptors

2021 ◽  
Vol 22 (15) ◽  
pp. 8257
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Mirissa Hewage Dumindu Kavinda ◽  
Hyung Won Ryu ◽  
Yung Hyun Choi ◽  
Jin-Woo Jeong ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Melanoma Cells ◽  
Gabab Receptors ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
B16f10 Melanoma ◽  
Melanocyte Stimulating Hormone ◽  
Zebrafish Larvae ◽  
B16f10 Melanoma Cells ◽  
Gabaa And Gabab Receptors

Gamma-aminobutyric acid (GABA) is considered the primary inhibitory neurotransmitter in the human cortex. However, whether GABA regulates melanogenesis has not been comprehensively elucidated. In this study, we reveal that GABA (20 mM) significantly inhibited α-melanocyte-stimulating hormone (α-MSH)-induced extracellular (from 354.9% ± 28.4% to 126.5% ± 16.0%) and intracellular melanin contents (from 236.7% ± 11.1% to 102.7% ± 23.1%) in B16F10 melanoma cells, without inducing cytotoxicity. In addition, α-MSH-induced hyperpigmentation in zebrafish larvae was inhibited from 246.3% ± 5.4% to 116.3% ± 3.1% at 40 mM GABA, displaying no apparent cardiotoxicity. We also clarify that the GABA-mediated antimelanogenic properties were related to the direct inhibition of microphthalmia-associated transcription factor (MITF) and tyrosinase expression by inhibiting cyclic adenosine monophosphate (cAMP) and cAMP response element-binding protein (CREB). Furthermore, under α-MSH stimulation, GABA-related antimelanogenic effects were mediated through the GABAA and GABAB receptors, with subsequent inhibition of Ca2+ accumulation. In B16F10 melanoma cells and zebrafish larvae, pretreatment with bicuculline, a GABAA receptor antagonist, and CGP 46381, a GABAB receptor antagonist, reversed the antimelanogenic effect of GABA following α-MSH treatment by upregulating Ca2+ accumulation. In conclusion, our results indicate that GABA inhibits α-MSH-induced melanogenesis. Hence, in addition to the health benefits of GABA in the central nervous system, it could ameliorate hyperpigmentation disorders.

scholarly journals GSK-3β-Targeting Fisetin Promotes Melanogenesis in B16F10 Melanoma Cells and Zebrafish Larvae through β-Catenin Activation

2020 ◽  
Vol 21 (1) ◽  
pp. 312 ◽  
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Wisurumuni Arachchilage Hasitha Maduranga Karunarathne ◽  
Sang Rul Park ◽  
Yung Hyun Choi ◽  
Eui Kyun Park ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Glycogen Synthase ◽  
Melanoma Cells ◽  
Functional Assay ◽  
Mushroom Tyrosinase ◽  
B16f10 Melanoma ◽  
Zebrafish Larvae ◽  
B16f10 Melanoma Cells ◽  
Gsk 3Β

Fisetin is found in many fruits and plants such as grapes and onions, and exerts anti-inflammatory, anti-proliferative, and anticancer activity. However, whether fisetin regulates melanogenesis has been rarely studied. Therefore, we evaluated the effects of fisetin on melanogenesis in B16F10 melanoma cell and zebrafish larvae. The current study revealed that fisetin slightly suppressed in vitro mushroom tyrosinase activity; however, molecular docking data showed that fisetin did not directly bind to mushroom tyrosinase. Unexpectedly, fisetin significantly increased intracellular and extracellular melanin production in B16F10 melanoma cells regardless of the presence or absence of α-melanocyte stimulating hormone (α-MSH). We also found that the expression of melanogenesis-related genes such as tyrosinase and microphthalmia-associated transcription factor (MITF), were highly increased 48 h after fisetin treatment. Pigmentation of zebrafish larvae by fisetin treatment also increased at the concentrations up to 200 µM and then slightly decreased at 400 µM, with no alteration in the heart rates. Molecular docking data also revealed that fisetin binds to glycogen synthase kinase-3β (GSK-3β). Therefore, we evaluated whether fisetin negatively regulated GSK-3β, which subsequently activates β-catenin, resulting in melanogenesis. As expected, fisetin increased the expression of β-catenin, which was subsequently translocated into the nucleus. In the functional assay, FH535, a Wnt/β-catenin inhibitor, significantly inhibited fisetin-mediated melanogenesis in zebrafish larvae. Our data suggested that fisetin inhibits GSK-3β, which activates β-catenin, resulting in melanogenesis through the revitalization of MITF and tyrosinase.

scholarly journals Jeju Magma-Seawater Inhibits α-MSH-Induced Melanogenesis via CaMKKβ-AMPK Signaling Pathways in B16F10 Melanoma Cells

Marine Drugs ◽  
2020 ◽  
Vol 18 (9) ◽  
pp. 473
Author(s):  
Minhyeok Song ◽  
Jihyun Lee ◽  
Young-Joo Kim ◽  
Dang Hieu Hoang ◽  
Wonchae Choe ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Skin Pigmentation ◽  
Adenosine Monophosphate ◽  
Melanoma Cells ◽  
Mitogen Activated Protein Kinase ◽  
B16f10 Melanoma ◽  
Ampk Signaling ◽  
Calcium Calmodulin Dependent ◽  
B16f10 Melanoma Cells

Melanin protects skin from ultraviolet radiation, toxic drugs, and chemicals. Its synthesis is sophisticatedly regulated by multiple mechanisms, including transcriptional and enzymatic controls. However, uncontrolled excessive production of melanin can cause serious dermatological disorders, such as freckles, melasma, solar lentigo, and cancer. Moreover, melanogenesis disorders are also linked to neurodegenerative diseases. Therefore, there is a huge demand for safer and more potent inhibitors of melanogenesis. In the present study, we report novel inhibitory effects of Jeju magma-seawater (JMS) on melanogenesis induced by α-melanocyte stimulating hormone (α-MSH) in B16F10 melanoma cells. JMS is the abundant underground seawater found in Jeju Island, a volcanic island of Korea. Research into the physiological effects of JMS is rapidly increasing due to its high contents of various minerals that are essential to human health. However, little is known about the effects of JMS on melanogenesis. Here, we demonstrate that JMS safely and effectively inhibits α-MSH-induced melanogenesis via the CaMKKβ (calcium/calmodulin-dependent protein kinase β)-AMPK (5′ adenosine monophosphate-activated protein kinase) signaling pathway. We further demonstrate that AMPK inhibits the signaling pathways of protein kinase A and MAPKs (mitogen-activated protein kinase), which are critical for melanogenesis-related gene expression. Our results highlight the potential of JMS as a novel therapeutic agent for ameliorating skin pigmentation-related disorders.

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