Selaginellin Inhibits Melanogenesis via the MAPK Signaling Pathway

Abstract

Hyperpigmented skin diseases such as melasma, freckles, and melanosis usually mar the appearance of patients. Traditional herbal medicines are highly accepted in inhibiting skin pigmentation, with advantages of high efficiency, low cost, and low side effects. Selaginellin (SEL), one of the active compounds of selaginella, has been proved to be exhibit antineoplastic, antioxidant, antisenescence, and antiapoptosis activities. In this study, we found that SEL can inhibit melanogenesis in vitro and in vivo. A mechanism study found that SEL inhibits melanogenesis through inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway, then down-regulating the expression of microphthalmia-associated transcription factor (MITF) and downstream genes tyrosinase (TYR) and tyrosinase-related protein 2 (TYRP2). UVB-activated paracrine function of fibroblasts and keratinocytes promotes melanogenesis of melanocytes. Interestingly, SEL antagonizes UVB-activated paracrine function of fibroblasts and keratinocytes. These findings indicate that SEL can be a potential whitening compound to inhibit melanogenesis.

Unveiling the Genetic Secrets of Chinese Indigenous Pigs from Guizhou Province: Diversity, Evolution and Candidate Genes Affecting Pig Coat Color

“…Zhou et al reported that Selaginellin (SEL) inhibited the mitogen-activated protein kinase (MAPK) signaling pathway. Then, the expression of microphthalmia-associated transcription factor (MITF ) and the downstream genes tyrosinase ( TYR ) and tyrosinase-associated protein 2 ( TYRP2 ) were downregulated to inhibit melanin production [ 26 ]. Interleukin-10 (IL-10) can activate the PI3K/Akt and JAK/Stat3 pathways, and the former leads to the activation of the classical NF-κB pathway and the inactivation of GSK-3β, further upregulating melanin production [ 27 ].…”

Fraxin inhibits melanogenesis by suppressing the ERK/MAPK pathway and antagonizes oxidative stress by activating the NRF2 pathway

“…Down-regulation of MAPK signaling is a promising way to develop agents for hyperpigmentation disorders [ 15 ]. In previous studies, some herbal extracts, such as selaginellin [ 16 ], isoliquiritigenin [ 17 ], can inhibited melanogenesis by deactivating ERK. Fraxin has also been reported to down-regulate ERK protein phosphorylation to protect hepatocytes from carbon tetrachloride (CCL4)-induced damage and to antagonize cerebral ischemia-reperfusion injury [ 11 , 18 ].…”

Stimulatory effects of Lycium shawii on human melanocyte proliferation, migration, and melanogenesis: In vitro and in silico studies

“…The methanolic extract of L. shawii leaves at the lowest tested concentration (i.e., 7.8 μg/mL), displayed a significant increase in human melanocyte proliferation without causing cytotoxicity at high concentrations (i.e., 500.0 μg/mL), and its effect was evaluated using additional experiments related to melanogenesis. Of note, skin melanocyte functions such as migration, proliferation, and melanogenesis are regulated by a complex network of extrinsic and intrinsic signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway and its downstream effector MITF, a transcription factor of melanogenesis-related gene expression ( Zhou et al, 2022 ). In addition, L. shawii , also known as the Arabian boxthorn, is a thorny shrub mainly found in the Arabian Peninsula.…”