• Archives of Pharmacal Research
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• v.24 no.2
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• pp.144-149
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• 2001

N-acetylsphingosine (C2-ceramide) is a synthetic water-soluble ceramide mimicking the activity of natural ceramides. By fixing chiral conformation on carbon numbers 2 and 3 in the ceramide structure, four chiral C2-ceramides naming d-erythro-, I-erythro-, d-threo-and 1-three C2-ceramide were synthesized. We have investigated the chiral effects of these C2-ceramides on the sphingolipid metabolism, particularly on both the sphingolipid bio- synthetic pathway and on the degradation pathway. In both HL-60 and U937 cells, the chiral C2-ceramide ($10{\mu}\textrm{m}$) showed sphingosine accumulation monitored fluoromatrically by a high performance liquid chromatographic separation of the sphingoid bases. Most importantly, in HL-60 cells, l-erythro C2-ceramide induced a 50 fold increase in sphingosine as compared to the control, while l-threo C2-ceramide exhibited a minimal 7-fold in-crease. In contrast, sphinganine, another sphingoid base, showed less accumulation by any chiral C2-ceramide tested under the same conditions. These results suggested that chiral C2-ceramide primarilyacts on the sphingolipid degradation pathway rather than on the sphingolipid biosynthetic route. The strong $C_0/G_1$ phase arrest in the cell cycle by treatment of I-erythro C2-ceramide indicates that the blockade of the sphingolipid degradation pathway might be concomitantly involved in the dysfunction of the cell cycle. On the other hand, the fact that all chiral C2-ceramides tested failed to inhibit the activity of sphingosine kinase acting on the removal of sphingosine by producing sphingosine-1 -phosphate demonstrates that chiral C2- ceramides may increase sphingosine by activating various ceramidases by which natural ceramides are divided into sphingosine and free fatty acids. However, the precise steps involved in this interaction are still unknown.

• Journal of Pharmaceutical Investigation
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• v.38 no.5
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• pp.319-323
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• 2008

For transdermal delivery of ceramides, various liposomes formulations were studied and evaluated. Sodium deoxycholate (SDC), Tween 20 and Span 85 were used as edge activators. The skin permeation of ceramides was performed using a Franz cell apparatus with hairless mouse skin. Among edge activators, SDC showed the higher values of deformability index and skin permeation than did others. For optimization of formulations, we varied the ratios of lipids to edge activators and the compositions between phosphatidylcholine (PC) and ceramides. The optimal ratio of lipid to SDC was observed to be 6:1 (w:w) and that of PC and ceramide was 1:1. Our results suggest that the skin permeation of ceramides could be enhanced by optimized deformable formulations of liposomes containing SDC as a major edge activator.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.34 no.1
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• pp.43-50
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• 2008

Ceramides, a constituent of stratum corneum lipids, play a crucial role in the formation and maintenance of the epidermal permeability barrier. As in many other skin disorders, atopic dermatitis and psoriasis show decrease and transformation of the ceramides. The application of ceramide has been demonstrated to be efficient in the repair of these skin disorders. Nevertheless, natural ceramides are still too expensive and small in quantity to be used as a cosmetic ingredient. Although a lot of pseudo-ceramides have been developed and on the market until now, those pseudo-ceramides did not fully meet the consumer's needs, therefore, there is still a demand for a novel pseudo-ceramides. We synthesized a novel pseudo-ceramide BPC-16 from 2-(2-amino-ethylamino)-ethanol(AEEA), which was characterized by structures having both amide bonds and hydroxyl groups as hydrophilic units, as well as two long alkyl chains. We formulated emulsion with BPC-16, cholesterol, stearic acid, and other components to make an emulsion. These emulsion showed a typical optical anisotropy on cross-polarized microscopy. This 'Maltese cross' appearance is a characteristic figure observed in concentric lamellar emulsion under cross-polarized microscopy. In cytotoxicity assay using MTT in monolayer and three dimension(3D) cell culture, a BPC-16 showed only negligible cytotoxicity up to the effective concentration for barrier repair and moisturization(less than 10 mM). In the measurement of TEWL, this BPC-16 showed significant recovery of water-retaining properties when it was topically applied to either SDS-induced dry skin or normal skin compared to that of base cream. This novel pseudo-ceramide BPC-16 showed as effective in skin barrier repair and moisturization as natural ceramides.

• Journal of Nutrition and Health
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• v.45 no.3
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• pp.211-217
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• 2012

UV-irradiation is a major factor of photo-aged skin, by which pigmentation, wrinkles and laxity are increased. In addition, the epidermal barrier is disrupted, ultimately causing dryness in photo-aged skin. As an effort to search dietary sources for improving the dryness of UV irradiated skin, the dietary effect of red ginseng based functional foods on the epidermal level of ceramides, a major lipid maintaining epidermal barrier, was determined in this study. Albino hairless mice were fed either a control diet [group UV (UV-irradiated control)] or diets with 0.5% (group M0.5) or 1% (group M1.0) of red ginseng extracts mixed with Torilis fructus and Corni fructus (66.7% red ginseng) in parallel with UV irradiation for 5 wks. A normal control group (group C) was fed a control diet without UV irradiation for 5 wks. The epidermal level of ceramides in group UV was significantly lower than that in group C, in which ceramidase, an enzyme involved in ceramide degradation, was highly expressed. In group M0.5, the epidermal level of ceramide was significantly increased to the level even higher than in group C. In addition, protein expression of serine palmitoyl transferase (SPT), a key enzyme involved in de novo ceramide synthesis, was increased in group M0.5. However the epidermal levels of ceramides as well as of ceramidase protein expression in group M1.0 did not differ from those in group UV. In conclusion, we demonstrate that dietary supplementation of red-ginseng extracts mixed with Torilis fructus and Corni fructus at a level of 0.5% level in diet increased the epidermal level of ceramides coupled with the elevated expression of SPT protein.

• Molecules and Cells
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• v.46 no.11
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• pp.688-699
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• 2023

We set up this study to understand the underlying mechanisms of reduced ceramides on immune cells in acute rejection (AR). The concentrations of ceramides and sphingomyelins were measured in the sera from hepatic transplant patients, skin graft mice and hepatocyte transplant mice by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Serum concentrations of C24 ceramide, C24:1 ceramide, C16:0 sphingomyelin, and C18:1 sphingomyelin were lower in liver transplantation (LT) recipients with than without AR. Comparisons with the results of LT patients with infection and cardiac transplant patients with cardiac allograft vasculopathy in humans and in mouse skin graft and hepatocyte transplant models suggested that the reduced C24 and C24:1 ceramides were specifically involved in AR. A ceramide synthase inhibitor, fumonisin B₁ exacerbated allogeneic immune responses in vitro and in vivo, and reduced tolerogenic dendritic cells (tDCs), while increased P3-like plasmacytoid DCs (pDCs) in the draining lymph nodes from allogeneic skin graft mice. The results of mixed lymphocyte reactions with ceranib-2, an inhibitor of ceramidase, and C24 ceramide also support that increasing ceramide concentrations could benefit transplant recipients with AR. The results suggest increasing ceramides as novel therapeutic target for AR, where reduced ceramides were associated with the changes in DC subsets, in particular tDCs.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.23 no.3
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• pp.92-96
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• 1997

Nowadays, ceramides have been found to be an important component in the outermost layer of the skin - the stratum corneum. It is undersrood that ceramides play an important role in structure and maintenance of the interellular lipid lamella structure in the SC layer. Thus, many efforts have been made by the cosmetics and pharmaceutical industries to get human skin-identical ceramides or pseudoceramides which show similar performance with natural ceramides. The purpose of our study was to systhesize new pseudoceramides via an effective and economical systhetic pathway and to show their performance of skin restoratio. Four kinds of the new pseudoceramides were synthesized by the reaction of alcoholic amine and alkyl ketene dimer. First of all, PC-4 and PC-5 were synthesized by the reaction of 3-amino-1,2-propanidiol and serinol with alkyl ketene dimer respectively. After that, PC-4R and PC-5R were produced by changign kitone group at $\beta$-position to amide bond of above synthesized PC-4 and PC-5 into hydroxyl group using NaBH4 respectively. Their expected structures were conformed by the NMR, IR spectra, and elemental analysis. A study to show the restoration effectiveness was performed in which human skin was pretreated with high concentration of SDS surfactant solution. Using 0.5% solution of above synthesized pseudoceramides, there was the significantly faster restoration of the damaged than that of placebe itself treatment.

• The Journal of Pediatrics of Korean Medicine
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• v.20 no.3
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• pp.129-141
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• 2006

Objectives : The purpose of this study is to determine clinical efficacy of herbal medicine by evaluating SCORAD Index and total level of ceramaides in the skin of 13 children with atopic dermatitis Methods : Subjects are divided into two groups : Group 1(non-differentiation children treated with Saenghyeoryunbueom) and group 2(differentiation children treated with either pyungwisan, onchungum or gamitongsungsan). We determine SCORAD Index and total level of ceramaides in the skin of 13 children with atopic dermatitis before and after taking each of herbal treatment for 12 weeks. Results : After herbal prescription for 12 weeks, A SCORAD index of both group 1 and group 2 was decreased. However, the total level of ceramides in group 1 and group 2 was not altered after 12 weeks. When the correlation between the alteration of SCORAD index and ceramides levels was determined, the SCORAD index in group 1 was inversely correlated with the total level of ceramides(r=-0.994, p=0.006) In contrast, the alteration of SCORAD index in group 2 was not correlated with ceramide levels. Conclusions : The clinical efficacy of Saenghyeoryunbueom for non-differentiation children with atopic dermatitis is paralleled with the increased level of ceramides in skin. The clinical efficacy of pyungwisan, onchungum or gamitongsungsan for differentiation children with atopic dermatitis is not correlated with ceramide level in skin.

• Molecules and Cells
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• v.43 no.5
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• pp.419-430
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• 2020

The liver is an important organ in the regulation of glucose and lipid metabolism. It is responsible for systemic energy homeostasis. When energy need exceeds the storage capacity in the liver, fatty acids are shunted into nonoxidative sphingolipid biosynthesis, which increases the level of cellular ceramides. Accumulation of ceramides alters substrate utilization from glucose to lipids, activates triglyceride storage, and results in the development of both insulin resistance and hepatosteatosis, increasing the likelihood of major metabolic diseases. Another sphingolipid metabolite, sphingosine 1-phosphate (S1P) is a bioactive signaling molecule that acts via S1P-specific G protein coupled receptors. It regulates many cellular and physiological events. Since an increase in plasma S1P is associated with obesity, it seems reasonable that recent studies have provided evidence that S1P is linked to lipid pathophysiology, including hepatosteatosis and fibrosis. Herein, we review recent findings on ceramides and S1P in obesity-mediated liver diseases and the therapeutic potential of these sphingolipid metabolites.

• Bulletin of the Korean Chemical Society
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• v.26 no.9
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• pp.1457-1460
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• 2005

• Journal of the Society of Cosmetic Scientists of Korea
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• v.24 no.3
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• pp.6-16
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• 1998

Ceramides are currently emerging as the major skin care ingredients due to !heir barrier properties in the stratum corneum of the human skin. Thus, major cosmetic companies have developed synthetic ceramide analogs for their own use. In this study, several ceramide mimic compounds , new skin barrier lipids, were designed and synthesized, and their physical and biological properties were investigated to evaluate their skin care capability. Several structures were designed from the variation of hydrophobic alkyl chain and hydrophilic moiety by the use of molecular modeling software. The selected targets were synthesized, and their properties and activities were studied as the pure form, in the emulsion, or in the lamellar mixture containing cholesterol and fatty acid. Some compounds, such as 1,3-bis(N-(2-hydroxyethyl)-palmitoylamino)-2-hydroxypropane, enhanced the restoration of skin barrier damaged by SDS(sodium dodecyl sulfate), and by acetone treatment. The rate of restoration was comparable to that of natural ceramides. The synthesized compounds alleviated SDS induced skin irritation and facilitated lamellar phase liquid crystal formation. The treatment of 1,3-Dis(N-(2-hydroxyethyl)-palmitoylam ino)-2-hyd roxypropane on the acetone damaged skin revealed that the compound promoted the recovery of intercellular lipid lamellar structure of stratum corneum layer. The replacement of palmitoyl groups of the compound with shorter alkyl chain gave lower emulsion viscosity and liquid crystal density, suggesting easier formulation and poorer barrier activity. Most of the synthesized compounds were non-irritable in various toxicological tests proving that they can be safely introduced to the skin care formulations.