ABSTRACT
The skin barrier prevents moisture evaporation and the entry of foreign substances such as allergens. Ceramides are one of the most important factors for maintaining skin barrier function. Melia toosendan is a plant of the Meliaceae family, and its fruit extracts have been used in Traditional Chinese Medicine as analgesics and anthelmintics; however, its ability to increase ceramide levels has not been reported. In this study, we screened for compounds present in M. toosendan fruit extracts that increase ceramide levels in the skin. We fractionated the extracts based on their activity to identify the active components. Nimbolinins, limonoids such as toosendanin, and hydroxylated unsaturated fatty acids were found to be the major active components. The structure-activity relationship of toosendanin derivatives indicated that the sites around R4 and R5 contributed to the activity. To the best of our knowledge, this is the first report showing that limonoids promote ceramide production in skin cells. Therefore, M. toosendan fruit extracts may be used to develop products for improving the skin barrier function.
Subject(s)
Ceramides/biosynthesis , Fatty Acids, Unsaturated/pharmacology , Keratinocytes/metabolism , Limonins/pharmacology , Melia/chemistry , Cells, Cultured , Drugs, Chinese Herbal , Fruit/chemistry , Humans , Japan , Molecular Structure , Structure-Activity RelationshipABSTRACT
The signaling of stem cell factor (SCF) through its receptor Kit is known to play an important role in regulating cutaneous melanogenesis. In the course of UVB-induced pigmentation, the expression of membrane-bound SCF by epidermal keratinocytes is upregulated at an early phase and subsequently activates neighboring melanocytes via their Kit receptors. In order to identify effective skin-lightening materials, we screened botanical extracts to determine their abilities to diminish Kit expression in melanocytes. A Platycodon root extract was consequently found to have a remarkable inhibitory activity on Kit expression. When the extract was applied to three-dimensional human skin substitutes in vitro and to human skin in vivo after UVB irradiation, their pigmentation was significantly reduced, confirming the substantial contribution of the suppression of SCF/Kit signaling to preventing or inhibiting melanin synthesis. These data demonstrate that a Platycodon root extract is a promising material for a skin-lightening product to improve pigmentation-related diseases.
Subject(s)
Platycodon , Proto-Oncogene Proteins c-kit/metabolism , Skin Lightening Preparations/pharmacology , Skin Pigmentation/drug effects , Animals , Cells, Cultured , Humans , Melanocytes/drug effects , Melanocytes/metabolism , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Stem Cell Factor/pharmacology , Ultraviolet RaysABSTRACT
The objective of this study was to clarify variations of the ceramide (CER) profile in human stratum corneum (SC) in different seasons and in different regions of the body and to estimate the contributions of CERs to the SC barrier and water-holding functions. Based on the information that there are great variations of SC functions among body sites, we compared the CER profiles obtained from ten different anatomical sites in healthy Japanese males in four seasons. Not only the physiological parameters of skin but also the CER profile showed body region and seasonal variations. The total CER level, the CER composition and the C34-CER[NS] species displayed strong correlations with the values of transepidermal water loss and capacitance throughout the body. Especially in the cheek, a strong correlation between the capacitance and the CER profile was observed. There were seasonal variations of the CER profile in the lip, upper arm and palm. Our results indicate that regional and seasonal variations of the CER profile may contribute to SC functions.
