Life Extension Skin Care Sale


LE Magazine September 2008

Foot care

Effects of 1,8-cineole on the dynamics of lipids and proteins of stratum corneum.

The interaction of a potent percutaneous penetration enhancer, 1,8-cineole, with the stratum corneum (SC) and DPPC membranes was investigated by electron paramagnetic resonance spectroscopy (EPR) of spin-labeled analogs of stearic acid (5-DSA) and androstanol (ASL). The EPR spectra of lipid derivatives spin probes structured in stratum corneum tissue of neonatal rat containing of 0.1-10% (v/v) 1,8-cineole in the solvent indicate an abrupt increase in membrane fluidity at around 1% 1,8-cineole. These spectra of stratum corneum membranes are characterized by the presence of two spectral components differing in mobility. Component 1 was attributed to the spin labels H-bonded to the headgroups, while component 2 possibly arose from spin labels H-bonded to water molecules or temporally non-hydrogen-bonded. With the addition of 1,8-cineole, the spin probes were transferred from the motionally more restricted component 1 to the more mobile component 2, suggesting that 1,8-cineole causes ruptures in the hydrogen-bonded network of the membrane-water interface, with consequent displacements of spin probes towards the hydrophobic core. 1,8-Cineole increased the rotational diffusion rates of component 2, whereas no significant mobility changes were observed in component 1. The EPR spectra of maleimide derivative spin label (6-MSL) covalently attached to stratum corneum proteins indicate that 1,8-cineole does not alter the dynamics of protein backbones. Instead, this terpene only increases the solvent’s ability to ‘dissolve’ and mobilize the nitroxide side chain, which is in agreement with its low irritation response.

Int J Pharm. 2007 Dec 10;345(1-2):81-7

Antibacterial, antifungal, and anticancer activities of volatile oils and extracts from stems, leaves, and flowers of Eucalyptus sideroxylon and Eucalyptus torquata.

Eucalyptus species leaves have been traditionally used to heal wounds and fungal infections. Essential oils and extracts of some Eucalyptus species possess antimicrobial and antitumor properties. We sought to determine antimicrobial and cytotoxic activities of oils and extracts of leaves, stems, and flowers of Eucalyptus sideroxylon and Eucalyptus torquata grown in Egypt. An agar diffusion method was used to analyze antimicrobial activities of essential oils and extracts of Eucalyptus against medically important gram-positive and gram-negative bacteria. A sulphorhodamine B assay was used to analyze the in vitro cytotoxic activities of oils and extracts against Human hepatocellular carcinoma cell line (HEPG2), and Human breast adenocarcinoma cell line (MCF7). Gram-positive bacteria were highly susceptible to oils and extracts of both Eucalyptus species. With the exception of Escherichia coli, gram-negative bacteria were resistant to extracts, but susceptible to the oil obtained from at least one organ of E sideroxylon and E torquata. Although Aspergillus flavus and Aspergillus niger were resistant to the extracts, essential oils of E sideroxylon and E torquata generally exhibited moderate to high antifungal activities against Candida albicans, A flavus and A niger. Oils of E torquata stems exhibited cytotoxic activities on MCF7 cells followed by oils of E torquata leaves and E sideroxylon leaves. However, oils from both species failed to exert cytotoxic effects on HEPG2 cells. This is the first report of antimicrobial and antitumor properties of E sideroxylon and E torquata. Results suggest a wider use of Eucalyptus species products in pharmaceutical, cosmetic, and food preparations.

Cancer Biol Ther. 2008 Mar;7(3):1-5

The menthol receptor TRPM8 is the principal detector of environmental cold.

Sensory nerve fibres can detect changes in temperature over a remarkably wide range, a process that has been proposed to involve direct activation of thermosensitive excitatory transient receptor potential (TRP) ion channels. One such channel—TRP melastatin 8 (TRPM8) or cold and menthol receptor 1 (CMR1)—is activated by chemical cooling agents (such as menthol) or when ambient temperatures drop below approximately 26 degrees C, suggesting that it mediates the detection of cold thermal stimuli by primary afferent sensory neurons. However, some studies have questioned the contribution of TRPM8 to cold detection or proposed that other excitatory or inhibitory channels are more critical to this sensory modality in vivo. Here we show that cultured sensory neurons and intact sensory nerve fibres from TRPM8-deficient mice exhibit profoundly diminished responses to cold. These animals also show clear behavioural deficits in their ability to discriminate between cold and warm surfaces, or to respond to evaporative cooling. At the same time, TRPM8 mutant mice are not completely insensitive to cold as they avoid contact with surfaces below 10 degrees C, albeit with reduced efficiency. Thus, our findings demonstrate an essential and predominant role for TRPM8 in thermosensation over a wide range of cold temperatures, validating the hypothesis that TRP channels are the principal sensors of thermal stimuli in the peripheral nervous system.

Nature. 2007 Jul 12;448(7150):204-8

Menthol-induced Ca2+ release from presynaptic Ca2+ stores potentiates sensory synaptic transmission.

Menthol and many of its derivatives produce profound sensory and mental effects. The receptor for menthol has been cloned and named cold- and menthol-sensitive receptor-1 (CMR1) or transient receptor potential channel M8 (TRPM8) receptor. Using a dorsal root ganglion (DRG) and dorsal horn (DH) coculture system as a model for the first sensory synapse in the CNS, we studied menthol effects on sensory synaptic transmission and the underlying mechanisms. We found that menthol increased the frequency of miniature EPSCs (mEPSCs). The effects persisted under an extracellular Ca2+-free condition but were abolished by intracellular BAPTA and pretreatment with thapsigargin. Menthol-induced increases of mEPSC frequency were blocked by 2-aminoethoxydiphenylborane (2-APB) but not affected by the phospholipase C inhibitor U73122 [GenBank] or by the cADP receptor inhibitor 8-bromo-cADPR (8Br-cADPR). Double-patch recordings from DRG-DH pairs showed that menthol could potentiate evoked EPSCs (eEPSCs) and change the paired-pulse ratio of eEPSCs. A Ca2+ imaging study on DRG neurons demonstrated that menthol could directly release Ca2+ from intracellular Ca2+ stores. Menthol-induced Ca2+ release was abolished by 2-APB but not affected by U73122 [GenBank] or 8Br-cADPR. Taken together, our results indicate that menthol can act directly on presynaptic Ca2+ stores of sensory neurons to release Ca2+, resulting in a facilitation of glutamate release and a modulation of neuronal transmission at sensory synapses. Expression of TRPM8 receptor on presynaptic Ca2+ stores, a novel localization for this ligand-gated ion channel, is also strongly suggested.

J Neurosci. 2004 Jan 21;24(3):762-71

Analgesic and anti-inflammatory effects of essential oils of Eucalyptus.

Many species of the genus Eucalyptus from the Myrtaceae family are used in Brazilian folk medicine for the treatment of various medical conditions such as cold, flue, fever, and bronchial infections. In the current investigation, we evaluated the analgesic and anti-inflammatory effects of essential oil extracts from three species of Eucalyptus employing various standard experimental test models. Using acetic acid-induced writhes in mice and hot plate thermal stimulation in rats, it was shown that the essential oils of Eucalyptus citriodora (EC), Eucalyptus tereticornis (ET), and Eucalyptus globulus (EG) induced analgesic effects in both models, suggesting peripheral and central actions. In addition, essential oil extracts from the three Eucalyptus species produced anti-inflammatory effects, as demonstrated by inhibition of rat paw edema induced by carrageenan and dextran, neutrophil migration into rat peritoneal cavities induced by carrageenan, and vascular permeability induced by carrageenan and histamine. However, no consistent results were observed for some of the parameters evaluated, both in terms of activities and dose-response relationships, reflecting the complex nature of the oil extracts and/or the assay systems used. Taken together, the data suggest that essential oil extracts of EC, ET, and EG possess central and peripheral analgesic effects as well as neutrophil-dependent and independent anti-inflammatory activities. These initial observations provide support for the reported use of the eucalyptus plant in Brazilian folk medicine. Further investigation is warranted for possible development of new classes of analgesic and anti-inflammatory drugs from components of the essential oils of the Eucalyptus species.

J Ethnopharmacol. 2003 Dec;89(2-3):277-83

More than cool: promiscuous relationships of menthol and other sensory compounds.

Several temperature-activated transient receptor potential (thermoTRP) ion channels are the molecular receptors of natural compounds that evoke thermal and pain sensations. Menthol, popularly known for its cooling effect, activates TRPM8--a cold-activated thermoTRP ion channel. However, human physiological studies demonstrate a paradoxical role of menthol in modulation of warm sensation, and here, we show that menthol also activates heat-activated TRPV3. We further show that menthol inhibits TRPA1, potentially explaining the use of menthol as an analgesic. Similar to menthol, both camphor and cinnamaldehyde (initially reported to be specific activators of TRPV3 and TRPA1, respectively) also modulate other thermoTRPs. Therefore, we find that many “sensory compounds” presumed to be specific have a promiscuous relationship with thermoTRPs.

Mol Cell Neurosci. 2006 Aug;32(4):335-43

A review of the bioactivity of South African herbal teas: rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia).

Rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) are popular tisanes in their native South Africa and have a growing worldwide market. Both herbal teas are used traditionally for medicinal purposes and are rich in polyphenols with rooibos a rare source of the dietary dihydrochalcones, aspalathin and nothofagin. The principal polyphenols in honeybush include the xanthone mangiferin and the flavonones hesperitin and isokuranetin. Despite their divergent phytochemical and nutrient compositions, rooibos and honeybush share potent antioxidant and antimutagenic activities in vitro. Animal model studies indicate both herbal teas possess potent antioxidant, immune-modulating and chemopreventive actions. However, human studies of rooibos are limited and of honeybush are absent. No adverse effects of rooibos or honeybush consumption as tisanes have been reported.

Phytother Res. 2007 Jan;21(1):1-16

Studies of the antioxidative effects of green and black tea (Camellia sinensis) extracts in rats.

This paper reports a comparative study of the antioxidative effects of black and green tea extracts in sodium oxalate-challenged rats. A dose of 10 mg/kg of body weight of sodium oxalate was used to induce lipid peroxidation in vivo. Rats treated with sodium oxalate had 42.06 +/- 3.10 nM/hour, 45.39 +/- 9.75 mg/100 mL, 10.95 +/- 1.52%, 15.95 +/- 3.19 mg/dL, 112.25 +/- 5.15 mg/dL, 59.21 +/- 2.95 IU, 39.55 +/- 2.51 IU, and 150.62 +/- 9.62 KA/unit for serum levels of malondialdehyde, reduced ascorbic acid, catalase, cholesterol, phospholipid, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), respectively. These values are significantly (P < .05) different from values obtained from normal rats. Rats pretreated with 100 mg/kg of body weight of green tea had 27.59 +/- 3.56 nM/hour, 79.11 +/- 5.13 mg/100 mL, 4.23 +/- 0.36%, 50.09 +/- 5.24 mg/dL, 97.58 +/- 4.73 mg/dL, 23.10 +/- 1.59 IU, 31.14 +/- 1.26 IU, and 96.48 +/- 2.36 KA/unit for serum levels of malondialdehyde, reduced ascorbic acid, catalase, cholesterol, phospholipid, AST, ALT, and ALP, respectively, compared with 37.28 +/- 2.07 nM/hour, 72.62 +/- 2.10 mg/100 mL, 6.23 +/- 1.52%, 37.25 +/- 2.84 mg/dL, 78.05 +/- 2.36 mg/dL, 36.08 +/- 1.80 IU, 29.00 +/- 3.02 IU, and 109.23 +/- 6.32 KA/unit recorded for the same parameters in rats treated with black tea. The cholesterol to phospholipid ratio was increased from 0.14 +/- 0.04 in control rats to 0.47 +/- 0.02 and 0.51 +/- 0.01 by black and green tea extracts, respectively. These results suggest that tea extracts have antioxidant properties and that green tea extract is more potent.

J Med Food. 2007 Jun;10(2):345-9

The effect of green, black and white tea on the level of alpha and gamma tocopherols in free radical-induced oxidative damage of human red blood cells.

The present study was undertaken to investigate the effect of aqueous tea extracts on lipid peroxidation and alpha and gamma tocopherols concentration in the oxidative damage of human red blood cells (RBC). RBC was taken as the model for study of the oxidative damage was induced by cumene hydroperoxide (cumOOH). The antioxidative property of leaf green tea, leaf and granulate of black tea and white tea at levels 1, 2, 4 g/150 mL of water were evaluated. The correlation was observed between reducing power of tea extract and formation of malondialdehyde--MDA (an indicator of lipid peroxidation) in oxidative damage of RBC. All tea extracts at level of 4 g/150 mL of water significantly decreased concentration of MDA. The extract of green tea in comparison to black and white tea extracts at the same levels seems to be a better protective agent against oxidative stress. The antioxidant synergism between components extracted from leaves of green tea and endogenous alpha tocopherol in the oxidative damage of red blood cells was observed. The consumption of alpha tocopherol in oxidative damage of RBC was the lowest after treatment with the highest dose of green tea extract. All tea extracts did not protect against decrease of gamma tocopherol in human erythrocytes treated with cumOOH.

Acta Pol Pharm. 2007 Mar-Apr;64(2):159-64

Skin photoprotection by green tea: antioxidant and immunomodulatory effects.

Because of a characteristic aroma and health benefits, green tea is consumed worldwide as a popular beverage. The epicatechin derivatives, commonly called polyphenols, present in green tea possess antioxidant, anti-inflammatory and anti-carcinogenic properties. The major and most highly chemopreventive constituent in green tea responsible for the biochemical or pharmacological effects is (-)-epigallocatechin-3-gallate (EGCG). Epidemiological, clinical and biological studies have implicated that solar ultraviolet (UV) light is a complete carcinogen and repeated exposure can lead to the development of various skin disorders including melanoma and nonmelanoma skin cancers. We and others have shown that topical treatment or oral consumption of green tea polyphenols (GTP) inhibit chemical carcinogen- or UV radiation-induced skin carcinogenesis in different laboratory animal models. Topical treatment of GTP and EGCG or oral consumption of GTP resulted in prevention of UVB-induced inflammatory responses, immunosuppression and oxidative stress, which are the biomarkers of several skin disease states. Topical application of GTP and EGCG prior to exposure of UVB protects against UVB-induced local as well as systemic immune suppression in laboratory animals, which was associated with the inhibition of UVB-induced infiltration of inflammatory leukocytes. Prevention of UVB-induced suppression of immune responses by EGCG was also associated with the reduction in immunosuppressive cytokine interleukin (IL)-10 production at UV irradiated skin and draining lymph nodes, whereas IL-12 production was significantly enhanced in draining lymph nodes. Antioxidant and anti-inflammatory effects of green tea were also observed in human skin. Treatment of EGCG to human skin resulted in the inhibition of UVB-induced erythema, oxidative stress and infiltration of inflammatory leukocytes. We also showed that treatment of GTP to human skin prevents UVB-induced cyclobutane pyrimidine dimers formation, which are considered to be mediators of UVB-induced immune suppression and skin cancer induction. The in vitro and in vivo animal and human studies suggest that green tea polyphenols are photoprotective in nature, and can be used as pharmacological agents for the prevention of solar UVB light-induced skin disorders including photoaging, melanoma and nonmelanoma skin cancers after more clinical trials in humans.

Curr Drug Targets Immune Endocr Metabol Disord. 2003 Sep;3(3):234-42

Recipes for reconstituting skin.

Reconstituted Living Skin Equivalent (LSE) is made up of a dermal equivalent (DE) on which keratinocytes are plated where they give rise to a multilayered differentiated epidermis. The dermal equivalent develops through interactions between fibroblasts and collagen fibrils that begin to form after the cell-matrix precursor is cast. The gel that forms as a result of collagen polymerization and fluid trapping is contracted uniformly in all dimensions. By securing it at ends and edges in the mold in which it is cast, the final dimensions, strength and morphology of the forming tissue are altered. The same phenomena are seen in casting tubular tissues for the fabrication of small caliber blood vessel equivalents. The cells of the dermal equivalent are biosynthetically active and enrich the matrix to different degrees with secretory products, depending on how the cells are stimulated and on the presence or absence of an epidermis. Collagen biosynthesis by dermal cells in the DE is sensitive to growth factors, ascorbate concentrations and amino acid pools. Both ascorbate and TGF beta 1 increase total collagen biosynthesis at least two-fold by one week after tissue formation. With TGF beta 1 present, the capacity of cells in the DE to synthesize collagen increases with time, over a two-week period. If ascorbate (200 micrograms/ml) is added just after the tissue is cast and daily thereafter, contraction lattice is blocked, and collagen biosynthesis is enhanced relative to contracted controls that had received 200 micrograms/ml ascorbate once. The increase was nearly an order of magnitude over that of controls and was coordinate with a comparable increase in hyaluronate and sulfated glycosaminoglycan (GAG) production as shown by TCA-precipitable glucosamine in the intercellular matrix of the DE. Both the LSE and the Living Dermal Equivalent (LDE) exhibit complex responses to UV radiation and to various chemicals that are greatly different from responses given by monolayered cells.

J Biomech Eng. 1991 May;113(2):113-9

Lipophilic antioxidants in human sebum and aging.

Skin surface lipids (SSL), a very complex mixture of sebum mixed to small amounts of epidermal lipids, mantle the human epidermis, thus representing the outermost protection of the body against exogenous oxidative insults. The present work is a systematic and quantitative analysis of upper-chest SSL and their content in antioxidants in 100 healthy volunteers, divided into five age groups using TLC, HPLC, and GC-MS methods. Further, the effect of exposing SSL in vitro to increasing doses of UV irradiation was examined. Straight monounsaturated and diunsaturated as well as branched monounsaturated fatty acids of triglycerides and pooled fractions were found to be higher at maturity than in childhood and in advancing age. Diunsaturated fatty acids were below 3% of the total and constituted exclusively of C18:2delta5,8, C20:2delta7,10, C18:2delta9,12. Squalene, vitamin E (vit. E) and Coenzyme Q10 (CoQ10) were found to increase from childhood to maturity to decrease again significantly in old age. Vitamin E and CoQ10 were the only known lipophilic antioxidants present in SSL. In spite of their low levels they were found to synergically inhibit the UV induced depletion of squalene, cholesterol and of unsaturated fatty acids of SSL. In fact, exposure of SSL to increasing amounts of UV irradiation led preferentially to lowering of the levels of vit. E and CoQ10. Four minimal erythema dose (MED) (5.6J/cm2) were able to deplete 84% vit. E and 70% ubiquinone, and only 13% squalene. Diunsaturated and monounsaturated fatty acids as well as cholesterol were unaffected even following 10 MED UV exposures, which produced a 26% loss of squalene. The same UV dose when applied in the absence of vit. E and CoQ10 produced a 90% decrease of squalene.

Free Radic Res. 2002 Apr;36(4):471-7

Palmitoleic acid isomer (C16:1delta6) in human skin sebum is effective against gram-positive bacteria.

The percent lipid composition of pooled human sebum analyzed by thin-layer chromatography was: ceramides (13%), fatty acid (47%), cholesterol (7%), cholesterol esters (2%), squalene (11%), triglycerides (3%), and wax esters (17%). Total sebum lipids (2- 4 mg/ml), sonicated into bacterial culture medium, caused 4- to 5-fold log reduction in growth of gram-positive bacteria, Staphylococcus aureus, Streptococcus salivarius and the anaerobe Fusobacterium nucleatum, but was ineffective against most gram-negative bacteria. Fractionation of the sebum lipids showed that both saturated and unsaturated fatty acids contained the bulk of the antimicrobial activity. Lauric acid (C12:0) was the most active saturated fatty acid. The unsaturated fatty acid, palmitoleic acid (C16:1delta6, cPA) was both the most predominant monoene and the most active antimicrobial fatty acid. Purified cPA (>99%) yielded typical minimal inhibitory concentration (MIC) values of 10-20 microg/ml against gram-positive bacteria. Organically synthesized cPA isomer gave MIC values comparable to the natural material. Both natural and synthetic cPA were found to be the most active sebum lipid fraction in blocking the adherence of a pathogenic strain of Candida albicans to porcine stratum corneum. Ethanol in combination with cPA exerts a synergistic bactericidal activity against gram-negative pathogenic bacteria, including Pseudomonas aeruginosa, Propionibacterium acnes, Escherichia coli, and several methacillin-resistant strains of S. aureus. Palmitoleic acid may be useful in topical formulations for treatment of secondary gram-positive bacterial infections, as a gram-positive bacteria antimicrobial in wound dressings, and as a natural gram-positive antimicrobial preservative in skin and hair care products.

Skin Pharmacol Appl Skin Physiol. 2003 May-Jun;16(3):176-87

Coconut fats.

In many areas of Sri Lanka the coconut tree and its products have for centuries been an integral part of life, and it has come to be called the “Tree of life”. However, in the last few decades, the relationship between coconut fats and health has been the subject of much debate and misinformation. Coconut fats account for 80% of the fat intake among Sri Lankans. Around 92% of these fats are saturated fats. This has lead to the belief that coconut fats are ‘bad for health’, particularly in relation to ischaemic heart disease. Yet most of the saturated fats in coconut are medium chain fatty acids whose properties and metabolism are different to those of animal origin. Medium chain fatty acids do not undergo degradation and re-esterification processes and are directly used in the body to produce energy. They are not as ‘bad for health’ as saturated fats. There is the need to clarify issues relating to intake of coconut fats and health, more particularly for populations that still depend on coconut fats for much of their fat intake. This paper describes the metabolism of coconut fats and its potential benefits, and attempts to highlight its benefits to remove certain misconceptions regarding its use.

Ceylon Med J. 2006 Jun;51(2):47-51