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

Abstract

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.

Rapid screening of novel tyrosinase inhibitory peptides from a pearl shell meat hydrolysate by molecular docking and the anti-melanin mechanism

“…In the MC1R/α-MSH signaling pathway, FLF downregulated the expression of CREB, indicating that FLF also had a certain regulatory effect on the MC1R/α-MSH signaling pathway. 39 In the MAPK signaling pathway, phosphorylation of ERK and JNK triggers MITF degradation and downregulates melanin production. 40 In the MAPK signaling pathway, phosphorylation of ERK and JNK triggers MITF degradation and downregulates melanin production.…”

Anti-Pigmentary Natural Compounds and Their Mode of Action

“…JMS activated CaMKKβ (calcium/calmodulin-dependent protein kinase β), which then activated AMPK (5 adenosine monophosphate-activated protein kinase). AMPK blocks α-MSH-induced MAPKs (mitogen-activated protein kinase) and PKA (Protein kinase A) signaling pathways, resulting in the inhibition of Tyrosinase activity, melanin secretion, and melanogenesis-related gene expression [41]. Pandina boryana extracts regulated the phosphorylation of ERK and inhibited the expression of melanogenesis-related protein via the MAPK pathway [42].…”

Suppression of Matrix Metallopeptidase-3 Expression in Human Dermal Fibroblasts by Decursin from Angelica gigas Nakai Root Extracts Fermented with Jeju Lava Seawater

“…http://dx.doi.org/10.20402/ajbc.2020.0120 으로 인해 심혈관 질환, 당뇨병, 비만, 암 증상에 긍정적인 영향을 끼 친다는 연구 보고가 있다 (Song et al, 2020). 본 연구에 사용된 제주 용암해수는 심해수와 유사한 광물 성분을 가지는 한편, 약 100-200 m의 지하에서 얻어지기에 심해수에 비해 더 경제적으로 이점을 가 진다 (Noh et al, 2010;Lee et al, 2019).…”