ABSTRACT
Skin cancer is the most common human malignancy worldwide and solar ultraviolet (UV) radiation is known to serve an important role in its pathogenesis. Natural candidate compounds with antioxidant, photoprotective and antimelanogenic effects were investigated against the background of skin photoprotective and antimelanogenic properties. Gomisin D, J and O are dibenzocyclooctadiene lignans present in Kadsura medicinal plants and possess several pharmacological activities. In this study, the functions and mechanisms underlying the effects of gomisin D, J and O in UVAand UVBirradiated keratinocytes and αmelanocyte stimulating hormone (αMSH)stimulated melanocytes were explored. Following UVA and UVB irradiation, keratinocytes were treated with gomisin D, J and O, and keratinocyte viability, lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) production and apoptosis were examined. The results demonstrated that gomisin D and J improved keratinocyte viability and reduced LDH release under UVA and UVB irradiation. Intracellular ROS production induced by UVA and UVB irradiation was suppressed by gomisin D and J. In addition, Annexin V and TUNEL staining analysis indicated that gomisin D and J have significant antiapoptotic effects on UVAand UVBirradiated keratinocytes. After αMSH stimulation, melanocytes were treated with gomisin D, J and O, and the changes in melanocyte viability, intracellular melanin content, intracellular tyrosinase activity, and mechanisms underlying these changes were examined. Gomisin D markedly inhibited the αMSHinduced increase in intracellular melanin content and tyrosinase activity. Mechanistically, gomisin D reduced the protein and mRNA expression levels of microphthalmiaassociated transcription factor (MITF), tyrosinase, tyrosinaserelated protein (TRP)1 and TRP2 in αMSHstimulated melanocytes. In addition, gomisin D markedly downregulated αMSHinduced phosphorylation of protein kinase A and cAMP response element binding protein, which are known to be present upstream of the MITF, tyrosinase, TRP1 and TRP2 genes. Overall, gomisin D has photoprotective and antimelanogenic effects; these findings provide a basis for the production of potential brightening and photoprotective agents using natural compounds such as gomisin D.
Subject(s)
Dioxoles/pharmacology , Lignans/pharmacology , Polycyclic Compounds/pharmacology , Radiation-Protective Agents/pharmacology , Apoptosis/drug effects , Cell Survival/drug effects , China , HaCaT Cells , Humans , Kadsura/metabolism , Keratinocytes/metabolism , Melanins/metabolism , Melanocytes/metabolism , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , Skin Neoplasms/metabolismABSTRACT
Kadsura coccinea (KC), a beneficial plant for human health, has been used for centuries in China, Thailand, and Korea in folk medicine and food. There is evidence supporting the biological effects of highly bioactive ingredients in KC such as lignans, triterpenoids, flavonoids, phenolic acids, steroids, and amino acids. In this study, we aimed to explore the effects, functions, and mechanisms of the extracts from KC root (KCR), stem (KCS), leaf (KCL), and fruit (KCF) in UVA and UVB-irradiated keratinocytes and α-melanocyte stimulating hormone (α-MSH)-stimulated melanocytes. First, the total polyphenol and flavonoid contents of KCR, KCS, KCL, and KCF and their radical scavenging activities were investigated. These parameters were found to be in the following order: KCL > KCR > KCS > KCF. UVA and UVB-irradiated keratinocytes were treated with KCR, KCS, KCL, and KCF, and keratinocyte viability, LDH release, intracellular ROS production, and apoptosis were examined. Our results demonstrated that KC extracts improved keratinocyte viability and reduced LDH release, intracellular ROS production, and apoptosis in the presence UVA and UVB irradiation. The overall photoprotective activity of the KC extracts was confirmed in the following order: KCL > KCR > KCS > KCF. Moreover, KC extracts significantly decreased the intracellular melanin content and tyrosinase activity in α-MSH-stimulated melanocytes. Mechanistically, KC extracts reduced the protein and mRNA expression levels of tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2) in α-MSH-stimulated melanocytes. In addition, these extracts markedly downregulated myophthalmosis-related transcription factor expression and cAMP-related binding protein phosphorylation, which is upstream of the regulation of Tyrosinase, TRP-1, and TRP-2. The overall anti-melanogenic activity of the KC extracts was established in the following order. KCL > KCR > KCS > KCF. Overall, the KC extracts exert photoprotective and anti-melanogenic effects, providing a basis for developing potential skin-whitening and photoprotective agents.