ω-O-Acylceramides but not ω-hydroxy ceramides are required for healthy lamellar phase architecture of skin barrier lipids.

Epidermal omega-O-acylceramides (ω-O-acylCers) are essential components of a competent skin barrier. These unusual sphingolipids with ultralong N-acyl chains contain linoleic acid esterified to the terminal hydroxyl of the N-acyl, the formation of which requires the transacylase activity of patatin-like phospholipase domain containing 1 (PNPLA1). In ichthyosis with dysfunctional PNPLA1, ω-O-acylCer levels are significantly decreased, and ω-hydroxylated Cers (ω-OHCers) accumulate. Here, we explore the role of the linoleate moiety in ω-O-acylCers in the assembly of the skin lipid barrier. Ultrastructural studies of skin samples from neonatal Pnpla1+/+ and Pnpla1-/- mice showed that the linoleate moiety in ω-O-acylCers is essential for lamellar pairing in lamellar bodies, as well as for stratum corneum lipid assembly into the long periodicity lamellar phase. To further study the molecular details of ω-O-acylCer deficiency on skin barrier lipid assembly, we built in vitro lipid models composed of major stratum corneum lipid subclasses containing either ω-O-acylCer (healthy skin model), ω-OHCer (Pnpla1-/- model), or combination of the two. X-ray diffraction, infrared spectroscopy, and permeability studies indicated that ω-OHCers could not substitute for ω-O-acylCers, although in favorable conditions, they form a medium lamellar phase with a 10.8 nm-repeat distance and permeability barrier properties similar to long periodicity lamellar phase. In the absence of ω-O-acylCers, skin lipids were prone to separation into two phases with diminished barrier properties. The models combining ω-OHCers with ω-O-acylCers indicated that accumulation of ω-OHCers does not prevent ω-O-acylCer-driven lamellar stacking. These data suggest that ω-O-acylCer supplementation may be a viable therapeutic option in patients with PNPLA1 deficiency.

Role of hypothalamic de novo ceramides synthesis in obesity and associated metabolic disorders.

BACKGROUND: Sphingolipid-mediated signalling pathways are described as important players in the normal functioning of neurons and nonneuronal cells in the central nervous system (CNS). SCOPE OF REVIEW: This review aims to show role of de novo ceramide synthesis in the CNS in controling key physiological processes, including food intake, energy expenditure, and thermogenesis. The corollary is a condition that leads to a dysfunction in ceramide metabolism in these central regions that can have major consequences on the physiological regulation of energy balance. MAJOR CONCLUSIONS: Excessive hypothalamic de novo ceramide synthesis has been shown to result in the establishment of central insulin resistance, endoplasmic reticulum stress, and inflammation. Additionally, excessive hypothalamic de novo ceramide synthesis has also been associated with changes in the activity of the autonomic nervous system. Such dysregulation of hypothalamic de novo ceramide synthesis forms the key starting point for the initiation of pathophysiological conditions such as obesity - which may or may not be associated with type 2 diabetes.

Structure-dependent absorption of atypical sphingoid long-chain bases from digestive tract into lymph.

BACKGROUND: Dietary sphingolipids have various biofunctions, including skin barrier improvement and anti-inflammatory and anti-carcinoma properties. Long-chain bases (LCBs), the essential backbones of sphingolipids, are expected to be important for these bioactivities, and they vary structurally between species. Given these findings, however, the absorption dynamics of each LCB remain unclear. METHODS: In this study, five structurally different LCBs were prepared from glucosylceramides (GlcCers) with LCB 18:2(4E,8Z);2OH and LCB 18:2(4E,8E);2OH moieties derived from konjac tuber (Amorphophallus konjac), from GlcCers with an LCB 18(9Me):2(4E,8E);2OH moiety derived from Tamogi mushroom (Pleurotus cornucopiae var. citrinopileatus), and from ceramide 2-aminoethyphosphonate with LCB 18:3(4E,8E,10E);2OH moiety and LCB 18(9Me):3(4E,8E,10E);2OH moiety derived from giant scallop (Mizuhopecten yessoensis), and their absorption percentages and metabolite levels were analyzed using a lymph-duct-cannulated rat model via liquid chromatography tandem mass spectrometry (LC/MS/MS) with a multistage fragmentation method. RESULTS: The five orally administered LCBs were absorbed and detected in chyle (lipid-containing lymph) as LCBs and several metabolites including ceramides, hexosylceramides, and sphingomyelins. The absorption percentages of LCBs were 0.10-1.17%, depending on their structure. The absorption percentage of LCB 18:2(4E,8Z);2OH was the highest (1.17%), whereas that of LCB 18:3(4E,8E,10E);2OH was the lowest (0.10%). The amount of sphingomyelin with an LCB 18:2(4E,8Z);2OH moiety in chyle was particularly higher than sphingomyelins with other LCB moieties. CONCLUSIONS: Structural differences among LCBs, particularly geometric isomerism at the C8-C9 position, significantly affected the absorption percentages and ratio of metabolites. This is the first report to elucidate that the absorption and metabolism of sphingolipids are dependent on their LCB structure. These results could be used to develop functional foods that are more readily absorbed.

Discovery of deoxyceramide analogs as highly selective ACER3 inhibitors in live cells.

Acid (AC), neutral (NC) and alkaline ceramidase 3 (ACER3) are the most ubiquitous ceramidases and their therapeutic interest as targets in cancer diseases has been well sustained. This supports the importance of discovering potent and specific inhibitors for further use in combination therapies. Although several ceramidase inhibitors have been reported, most of them target AC and a few focus on NC. In contrast, well characterized ACER3 inhibitors are lacking. Here we report on the synthesis and screening of two series of 1-deoxy(dihydro)ceramide analogs on the three enzymes. Activity was determined using fluorogenic substrates in recombinant human NC (rhNC) and both lysates and intact cells enriched in each enzyme. None of the molecules elicited a remarkable AC inhibitory activity in either experimental setup, while using rhNC, several compounds of both series were active as non-competitive inhibitors with Ki values between 1 and 5 µM. However, a dramatic loss of potency occurred in NC-enriched cell lysates and no activity was elicited in intact cells. Interestingly, several compounds of Series 2 inhibited ACER3 dose-dependently in both cell lysates and intact cells with IC50's around 20 µM. In agreement with their activity in live cells, they provoked a significant increase in the amounts of ceramides. Overall, this study identifies highly selective ACER3 activity blockers in intact cells, opening the door to further medicinal chemistry efforts aimed at developing more potent and specific compounds.

Terminaliamide, a new ceramide and other phytoconstituents from the roots of Terminalia mantaly H. Perrier and their biological activities.

Terminaliamide (1), a new ceramide was isolated from the roots of Terminalia mantaly H. Perrier (Combretaceae) along with 4 known compounds (2-5). The structures of the compounds were elucidated using 1D and 2D NMR spectroscopy analysis and mass spectrometry. Compound 1 exhibited moderated antibacterial activity towards Staphylococcus aureus with MIC value of 62.5 µg/mL. The crude MeOH extract (TMr) highly reduced Plasmodium falciparum growth with an IC50 value of 10.11 µg/mL, while hexane fraction (F1) highly reduced Trypanosoma brucei brucei growth with an IC50 value of 5.60 µg/mL. All tested samples presented little or no in vitro cytotoxicity on HeLa cell line. The present work confirms that T. mantaly is medicinally important and may be used effectively as an antimicrobial, an antiplasmodial and an antitrypanosomial with promising therapeutic index.

The impact of EPA and DHA on ceramide lipotoxicity in the metabolic syndrome.

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including obesity, insulin resistance (IR) and dyslipidaemia. Consumption of a high-fat diet (HFD) enriched in SFA leads to the accumulation of ceramide (Cer), the central molecule in sphingolipid metabolism. Elevations in plasma and tissue Cer are found in obese individuals, and there is evidence to suggest that Cer lipotoxicity contributes to the MetS. EPA and DHA have shown to improve MetS parameters including IR, inflammation and hypertriacylglycerolaemia; however, whether these improvements are related to Cer is currently unknown. This review examines the potential of EPA and DHA to improve Cer lipotoxicity and MetS parameters including IR, inflammation and dyslipidaemia in vitro and in vivo. Current evidence from cell culture and animal studies indicates that EPA and DHA attenuate palmitate- or HFD-induced Cer lipotoxicity and IR, whereas evidence in humans is greatly lacking. Overall, there is intriguing potential for EPA and DHA to improve Cer lipotoxicity and related MetS parameters, but more research is warranted.

Assembly pattern of multicomponent supramolecular oleogel composed of ceramide and lecithin in sunflower oil: self-assembly or self-sorting?

Ceramide (CER) is a novel food-grade organogelator with beneficial health effects. Lecithin (LEC) is not an effective gelator; however, it may alter the crystal morphology of the host gelator in a multicomponent system. In this paper, LEC and CER were mixed at various molar ratios in sunflower oil leading to different gelation behaviors. It was interesting since in this multicomponent system, gels formed when there was more less-effective gelator (LEC), while gels hardly formed when there was more effective gelator (CER). This drew our attention since there might not be only one kind of assembly mode between the LEC and the CER. A comprehensive rheological investigation was conducted. It was found that at specific ratios (6L4C and 5L5C), strong gels (G' > 1.0 × 105 Pa) formed with superior oil binding capacity (up to 99.84%). Meanwhile, these gels exhibited higher tolerance level to permanent deformation than the monocomponent gel. However, weak gels were observed off the optimal ratio (8L2C, 7L3C, 4L6C and 3L7C). The crystal morphology of gels drastically changed with change in gelator proportion. Short needle-like crystals and small rosette crystals were observed in 6L4C and 5L5C, respectively, while other samples exhibited spherulite-shaped crystals (8L2C, 7L3C, 4L6C, and 3L7C), which differed from any of the monocomponent gel structures (10L0C and 0L10C). Results from differential scanning calorimetry and polarized light microscopy suggested that the macroscopic properties are determined by the morphology and distribution of crystals rather than the crystallinity of the matrix. Fourier transform infrared spectroscopy results indicated the presence of van der Waals forces and the formation of hydrogen bonding between the phosphate of the LEC and the amide group of the CER. The above results indicated that the LEC and CER co-assembled at approximately equal molar ratio, and the redundant LEC or CER at other ratios self-sorted to combine with the co-assembled fibers by lateral association, leading to potentially different underlying microstructures. These multicomponent supramolecular oleogels with high tunability may further broaden their applicability in various healthy lipid-based product formats.

Lecithin-Based Dermal Drug Delivery for Anti-Pigmentation Maize Ceramide.

Ceramides have several well-known biological properties, including anti-pigmentation and anti-melanogenesis, which make them applicable for use in skincare products in cosmetics. However, the efficacy of ceramides is still limited. Dermal or transdermal drug delivery systems can enhance the anti-pigmentation properties of ceramides, although there is currently no systemic evaluation method for the efficacy of these systems. Here we prepared several types of lecithin-based emulsion of maize-derived glucosylceramide, determining PC70-ceramide (phosphatidylcholine-base) to be the safest and most effective anti-pigmentation agent using zebrafish larvae. We also demonstrated the efficacy of PC70 as a drug delivery system by showing that PC70-Nile Red (red fluorescence) promoted Nile Red accumulation in the larval bodies. In addition, PC70-ceramide suppressed melanin in mouse B16 melanoma cells compared to ceramide alone. In conclusion, we developed a lecithin-based dermal delivery method for ceramide using zebrafish larvae with implications for human clinical use.

Engineering water-induced ceramide/lecithin oleogels: understanding the influence of water added upon pre- and post-nucleation.

A mixture of ceramide (CER) and lecithin (LEC) at specific ratios was capable of forming oleogels in sunflower oil triggered by adding a trace amount of water. It was noted that the addition of water at different temperatures (TW) resulted in different gelation behaviors and microstructures. To better illuminate the assembly mechanism at different TW, samples with water added at different TW (20 °C, 45 °C, 70 °C and 95 °C) were prepared. The viscoelastic properties, microstructures, and the crystal packing of these samples were investigated. It was observed that all samples prepared at TW of 20 °C and 95 °C formed gels, while most samples prepared at TW of 45 °C and 70 °C were too weak to form gels. Gels prepared at 95 °C were stronger but more fragile in texture compared to gels produced at 20 °C. The crystal morphology of gels drastically changed with TW. Spindle-shaped crystals were observed in gels prepared at low TW (20 °C), while gels prepared at high TW (95 °C) exhibited a network with packed oil droplets stabilized by lamellar shells together with fibrillar crystals in the bulk phase. X-ray diffractograms showed a different reflection peak (d-spacing of 14.5 Å) in gel prepared at 20 °C, compared to the d-spacing in oleogels with a single gelator (13.14 Å and 15.33 Å, respectively, for CER and LEC). Gel prepared at 95 °C showed two long-spacing characteristic peaks, which correspond to the characteristic peaks of CER gel (∼13 Å) and LEC gel (∼12 Å). Fourier transform infrared spectroscopy results indicated that the different gelation behaviors at different TW were mainly caused by vibrational changes in the amide bond of CER. Our hypothesized assembly mechanism can be concluded as: increasing TW resulted in the conversion of CER and LEC crystallization from co-assembly (TW = 20 °C) to self-sorting by individual gelators (TW = 95 °C). In this study, novel water-induced oleogels were produced by manipulating TW, and such information further assists the rational design of lipid-based healthy fat products.

Changes in IR band areas and band shifts during water adsorption to lecithin and ceramide.

Adsorption of water to a phospholipid (lecithin) and a ceramide were studied by IR microspectroscopy equipped with a humidity control system and quartz crystal microbalance (QCM). The water weight ratios increase up to 12.2 wt% for lecithin and 1.2 wt% for ceramide at RH ~80%, with linear correlations with infrared OH (+NH) band areas. For lecithin, the 1230 cm-1 band (PO2-) and the 1735 cm-1 band (CO) shift to lower wavenumbers, while the 1060 cm-1 band (PO2-, POC) shift to higher wavenumber with RH. Band areas of phosphates (1230 and 1060 cm-1) increase with RH showing positive relations with the band area of bound water. Bound water molecules with shorter H bonds might be bound to these phosphate groups. Band areas of aliphatic CHs are negatively correlated with the increasing adsorption of free water. Free water molecules with longer H bonds might interact loosely with aliphatic chains of lecithin. For ceramide, only the 1045 cm-1 band (CO) shows a small red shift at higher RHs than 60%, indicating adsorption of bound water to CO bonds. Amounts of water molecules adsorbed to ceramide are very limited due to few adsorption of free water.

Water-induced self-assembly of mixed gelator system (ceramide and lecithin) for edible oil structuring.

Ceramide (CER) is a highly effective organogelator with numerous health implications. Lecithin (LEC) is often used as a crystal modifier to improve gel properties. It was found in this study that in the presence of a small amount of water, CER and LEC self-assembled at specific ratios and form oleogels in sunflower oil (SFO), and the structure of which differed from any of the mono-component gel structures. To the best of our knowledge, this is the first water-induced multi-component oleogelation reported to date. To clarify when gelation occurs, a phase diagram of the four-component system SFO/CER/LEC/water was established and characterized. In the gel region, confocal laser scanning microscopy revealed that water was evenly distributed in the self-assembled microstructure. To clarify the vital role of water in formation of stable gel, a series of samples with varying ratios in CER and LEC with and without water were explored. The thermal properties, viscoelastic properties, microstructures, as well as crystal packing were investigated. With water added, the microscopic structures of CER/LEC gels changed from three-dimensional dendritic crystals to two-dimensional rod-like or platelet-like crystals, which are more effective at structuring liquid oil. A different reflection was observed (d-spacing of 14.9 Å), suggesting the rearrangement in crystal packing of ceramide and lecithin molecules, compared to the d-spacing in oleogels with single gelator (13.1 Å and 15.3 Å, respectively for ceramide and lecithin). Fourier transform infrared spectroscopy results indicated the presence of interaction between water and gelators, which confirmed the importance of water in self-assembly of this mixed-gelator system. Water-induced conversion of oleogelation provides alternatives in producing hard-stock fat replacers as well as possibilities to incorporate water-soluble nutrients into oil-based products.

Isolation of Ceramides from Tagetes patula L. Yellow Flowers and Nematicidal Activity of the Fractions and Pure Compounds against Cyst Nematode, Heterodera zeae.

Investigation of yellow flower extract of Tagetes patula L. led to the identification of an aggregate of five phytoceramides. Among them, (2R)-2-hydroxy-N-[(2S,3S,4R,8E)-1,3,4-trihydroxyicos-8-en-2-yl]icosanamide, (2R)-2-hydroxy-N-[(2S,3S,4R,8E)-1,3,4-trihydroxyicos-8-en-2-yl]heneicosanamide, (2R)-2-hydroxy-N-[(2S,3S,4R,8E)-1,3,4-trihydroxyicos-8-en-2-yl]docosanamide, and (2R)-2-hydroxy-N-[(2S,3S,4R,8E)-1,3,4-trihydroxyicos-8-en-2-yl]tricosanamide were identified as new compounds and termed as tagetceramides, whereas (2R)-2-hydroxy-N-[(2S,3S,4R,8E)-1,3,4-trihydroxyicos-8-en-2-yl]tetracosanamide was a known ceramide. A steroid (ß-sitosterol glucoside) was also isolated from the subsequent fraction. The structures of these compounds were determined on the basis of spectroscopic analyses, as well as chemical method. Several other compounds were also identified by GC/MS analysis. The fractions and some commercial products, a ceramide HFA, ß-sitosterol, and stigmasterol were evaluated against an economically important cyst nematode, Heterodera zeae. Ceramide HFA showed 100 % mortality, whereas, ß-sitosterol and stigmasterol were 40-50 % active, at 1 % concentration after 24 h of exposure time, while ß-sitosterol glucoside revealed no activity against the nematode.

Efficacy of a moisturizer containing a pseudo-ceramide and a eucalyptus extract for Japanese patients with mild atopic dermatitis in the summer.

BACKGROUND: Skin moisturizing is advocated to take care of the skin of patients with atopic dermatitis (AD). However, many patients stop using moisturizers in the summer because of excessive sweating and high humidity. OBJECTIVES: To examine the efficacy of a moisturizing gel containing a pseudo-ceramide and a eucalyptus extract, which enhances epidermal ceramide synthesis of patients with mild AD in the summer. METHODS: We performed a single-blinded 4-week clinical trial of body care on 44 Japanese subjects who had mild AD. They had not applied any moisturizer on their body in the summer. Twenty-seven subjects used the moisturizing gel containing a pseudo-ceramide and a eucalyptus extract twice a day and the 17 other subjects did not use any moisturizer. Prior to and at the end of weeks 2 and 4, the skin conditions of each subject were evaluated. RESULTS: During the test period, the atmospheric temperature increased and skin dryness and scaling significantly improved with or without application of the moisturizing gel. However, the improvement in dryness of the treated group was significantly higher than that of the nontreated group. Erythema and itchiness were significantly improved only in the treated group. The skin hydration on the forearm increased significantly only in the treated group. Accompanying those improvements, the quality of life of the subjects, evaluated by Skindex-16® , was significantly improved. CONCLUSION: The usage of a moisturizer containing a pseudo-ceramide and a eucalyptus extract is effective for care of the skin of AD subjects even in the summer.

Strawberry seed extract and its major component, tiliroside, promote ceramide synthesis in the stratum corneum of human epidermal equivalents.

The activation of peroxisomeproliferator-activated receptor (PPAR) α can stimulate the expression of ceramide-related enzymes, and a major component of strawberry seed extract (SSE) tiliroside enhances the expression of PPARα. We determined whether SSE and tiliroside may stimulate ceramide synthesis in the stratum corneum (SC) of the human epidermal equivalents (HEEs) culture model. Treatment with SSE at 1.0 and 3.0 µg/mL elicited a significant increase in the total ceramide content in the SC, which was accompanied by a significant increase in almost all ceramide species except for ceramide [EOS] and [AP]. Treatment with tiliroside at 0.3 µg/mL slightly accentuated the total ceramide content in the SC together with a significant increase in the ceramide [NS, NDS] content. Messenger RNA analysis demonstrated that SSE at 1 or 3 µg/mL significantly stimulated the gene expression of serine palmitoyltransferase (SPT) 2, ceramide synthase (CerS) 3, glucosylceramide synthase (GCS), and ß-glucocerebrosidase (GBA) but not of SPT1, sphingomyelin synthase (SMS) 1/2 and acid sphingomyelinase (ASM). In contrast, tiliroside elicited significant increases in the gene expression levels of GCS and GBA only at 0.3 and/or 0.1 µg/mL. Western blotting analysis revealed that both SSE and tiliroside enhanced the protein expression levels of GCS and GBA but not of SPT2 at 1 or 3 and 0.1 or 0.3 µg/mL, respectively. These findings suggested that both SSE and tiliroside have a distinct potential to stimulate the level of ceramide [NS, NDS] in the SC by enhancing the expression of GCS and GBA. The higher stimulatory effect with SSE than tiliroside on SC ceramide synthesis correlates with the significant increase observed with SSE but not tiliroside in the gene expression levels of SPT2 and CerS3. Therefore, it is anticipated that SSE is effective in improving skin barrier function and moisture retention in several ceramide-deficit skin conditions, including surfactant-induced roughened skin, xerosis, and atopic dermatitis.

Isolation and Structure Determination of Antiproliferative Secondary Metabolites from the Potato Earthball Mushroom, Scleroderma bovista (Agaricomycetes).

Mycochemical examination of a methanol extract of Scleroderma bovista Fr. (Agaricomycetes) led to the isolation of 7 compounds, which were, to our knowledge, identified for the first time in this species. The chemical structures of these compounds were determined through extensive spectroscopic methods (nuclear magnetic resonance and mass spectrometry). The fungal metabolites were identified as steroids based on ergostane (compounds 1-4) and lanostane (compounds 6 and 7) skeletons, whereas compound 5 was a ceramide derivative. We evaluated the antiproliferative activity of compounds 4-7 against human cancer cell lines (HeLa, A2780, MDA-MB-231, and MCF-7) using the MTT assay. The lanostane-type derivatives (compounds 6 and 7) and ergosterol peroxide 3-glucoside (compound 4) exerted significant antiproliferative property on 1 or more human cancer cell lines.

Delivery of oat-derived phytoceramides into the stratum corneum of the skin using nanocarriers: Formulation, characterization and in vitro and ex-vivo penetration studies.

Deficiency or altered composition of stratum corneum (SC) lipids such as ceramides (CERs), causing skin barrier dysfunction and skin dryness, have been associated with skin diseases such as atopic dermatitis and psoriasis, and ageing. Replenishing the depleted native CERs with exogenous CERs has also been shown to have beneficial effects in restoring the skin barrier. Phyto-derived CERs such as oat CERs were shown to be potential for skin barrier reinforcement. To effect this, however, the oat CERs should overcome the SC barrier and delivered deep into the lipid matrix using the various novel formulations. In an attempt to demonstrate the potential use of oat CERs, lecithin-based microemulsions (MEs) and starch-based nanoparticles (NPs) were formulated and characterized. Besides, ME gel and NP gel were also prepared using Carbopol®980 as a gelling agent. The in vitro release and penetration (using artificial four-layer membrane system) and ex vivo permeation (using excised human skin) of oat CERs from the various formulations were investigated. The results revealed ME enhanced the in vitro release and penetration oat CERs compared to the other formulations. On the other hand, the NPs retarded the release of oat CERs and small quantities of oat CERs incorporated into NP gel penetrated into the deeper layers of the multilayer membranes. The penetration-enhancing effect of ME was also observed in the ex vivo permeation studies where significant quantities of oat CERs were found in the acceptor compartment. Compared to the ME, the ME gel exhibited reduced depth and extent of oat CERs permeation. As compared to NP gel, ME gel enhanced the degree of permeation of oat CERs into the deeper layer of the skin. Generally the gel formulations were effective in concentrating oat CERs in the SC where they are needed to be.

Potential Applications of Phyto-Derived Ceramides in Improving Epidermal Barrier Function.

The outer most layer of the skin, the stratum corneum, consists of corneocytes which are coated by a cornified envelope and embedded in a lipid matrix of ordered lamellar structure. It is responsible for the skin barrier function. Ceramides (CERs) are the backbone of the intercellular lipid membranes. Skin diseases such as atopic dermatitis and psoriasis and aged skin are characterized by dysfunctional skin barrier and dryness which are associated with reduced levels of CERs. Previously, the effectiveness of supplementation of synthetic and animal-based CERs in replenishing the depleted natural skin CERs and restoring the skin barrier function have been investigated. Recently, however, the barrier function improving effect of plant-derived CERs has attracted much attention. Phyto-derived CERs (phytoCERs) are preferable due to their assumed higher safety as they are mostly isolated from dietary sources. The beneficial effects of phytoCER-based oral dietary supplements for skin hydration and skin barrier reinforcement have been indicated in several studies involving animal models as well as human subjects. Ingestible dietary supplements containing phytoCERs are also widely available on the market. Nonetheless, little effort has been made to investigate the potential cosmetic applications of topically administered phytoCERs. Therefore, summarizing the foregoing investigations and identifying the gap in the scientific data on plant-derived CERs intended for skin-health benefits are of paramount importance. In this review, an attempt is made to synthesize the information available in the literature regarding the effects of phytoCER-based oral dietary supplements on skin hydration and barrier function with the underlying mechanisms.

Soft coral Cespitularia stolonifera: New cytotoxic ceramides and gastroprotective activity.

In the present study, a new ceramide, namely 2S, 3R-4E, 8E-2-(heptadecanoylamino)-heptadeca-4, 8-diene-1, 3-diol (1), along with four known steroids, including 24-methylcholesta-5, 24(28)-diene-3ß-ol (2), 24-methylcholesta-5, 24(28)-diene-3ß-acetate (3), 4-methyl-24-methylcholesta-22-ene-3-ol (4), and cholesterol, was isolated and characterized from CH2Cl2/MeOH extract of Cespitularia stolonifera. A new acetate derivative of compound 1, termed 2S, 3R-4E, 8E-2-(heptadecanoylamino)-heptadeca-4, 8-diene-1, 3-diacetate (1a), was also prepared in the present study. All the structures were established on the basis of modern spectroscopic techniques, including FT-IR, 1D, 2D-NMR, HRESI-MS, and GC-MS, in addition of chemical methods. (-)-Alloaromadendren, ledane, (1)-alloaromadendren oxide, isoaromadendrene epoxide and (-)-caryophellen oxide were identified from the n-hexane fraction using GC-MS. The extract and the two ceramides (1) and (1a) exhibited significant cytotoxic activity against lung cancer A549 cells, while the extract and the two steroids (2) and (3) exhibited significant cytotoxic activity against breast cancer MCF-7 cells. The CH2Cl2/MeOH extract exhibited significant antiulcer activity in both ethanol and acetic acid induced ulcer models in rats, as evidenced by histopathological, histochemical, and biochemical examinations.

Production of Rare Phyto-Ceramides from Abundant Food Plant Residues.

Ceramides (Cers) are major components of the outermost layer of the skin, the stratum corneum, and play a crucial role in permeability barrier functions. Alterations in Cer composition causing skin diseases are compensated with semisynthetic skin-identical Cers. Plants constitute new resources for Cer production as they contain glucosylceramides (GluCers) as major components. GluCers were purified from industrial waste plant materials, apple pomace (Malus domestica), wheat germs (Triticum sp.), and coffee grounds (Coffea sp.), with GluCer contents of 28.9 mg, 33.7 mg, and 4.4 mg per 100 g of plant material. Forty-five species of GluCers (1-45) were identified with different sphingoid bases, saturated or monounsaturated α-hydroxy fatty acids (C15-28), and ß-glucose as polar headgroup. Three main GluCers were hydrolyzed by a recombinant human glucocerebrosidase to produce phyto-Cers (46-48). These studies showed that rare and expensive phyto-Cers can be obtained from industrial food plant residues.

Self gelating isoracemosol A, new racemosaceramide A, and racemosol E from Barringtonia racemosa.

Phytochemical investigation into the CHCl3 extract of the fruits of Barringtonia racemosa resulted in the isolation of two new metabolites along with isoracemosol A and betulinic acid as known metabolites. The new compounds were characterised as phytosphingosine-type ceramide [(2S,3S,4R)-2-[(2R)-2-hydroxyhexadecanoyl amino]-hexacos-8(E)-ene-1,3,4-triol, 1] and racemosol E [21ß-acetoxy-22α-(2-methylbutyroxy)-olean-12-ene-3ß,16α,28-triol, 2] on the basis of extensive spectroscopic data analysis and chemical modifications. In addition, the self-gelating property of isoracemosol A (3) was investigated for the first time, which leads to the unexpected agglomerated porous-like morphology.