Skin Changes During Ageing.

The skin provides the primary protection for the body against external injuries and is essential in the maintenance of general homeostasis. During ageing, resident cells become senescent and the extracellular matrix, mainly in the dermis, is progressively damaged affecting the normal organization of the skin and its capacity for repair. In parallel, extrinsic factors such as ultraviolet irradiation, pollution, and intrinsic factors such as diabetes or vascular disease can further accelerate this phenomenon. Indeed, numerous mechanisms are involved in age-induced degradation of the skin and these also relate to non-healing or chronic wounds in the elderly. In particular, the generation of reactive oxygen species seems to play a major role in age-related skin modifications. Certainly, targeting both the hormonal status of the skin or its surface nutrition can slow down age-induced degradation of the skin and improve healing of skin damage in the elderly. Skin care regimens that prevent radiation and pollution damage, and reinforce the skin surface and its microbiota are among the different approaches able to minimize the effects of ageing on the skin.

Two New Stilbenoids from the Aerial Parts of Arundina graminifolia (Orchidaceae).

Two new phenanthrene derivatives, a phenanthrenequinone named arundiquinone (1) and a 9,10-dihydrophenanthrene named arundigramin (2) together with a known lignin dimer (3) and seven known stilbenoids (4-10) were isolated from the aerial parts of the Asian orchid Arundina graminifolia. The structures of the isolated compounds were elucidated by spectroscopic methods, including extensive 1D, 2D NMR (heteronuclear single quantum coherence (HSQC), heteronuclear multiple-bond correlation spectroscopy (HMBC), and HR-ESI-MS techniques, as well as comparison with respective literature reports. The cytoprotective activity of the isolated compounds were evaluated for their ability to reduce beta amyloid induced toxicity on undifferentiated PC12 cells. Compound 8 showed moderate cytoprotective activity at 0.5 µmol/L (71% of cell viability) while the other compounds showed no significant activity at the highest concentration tested.

Chemical Constituents from the Aerial Parts of Cyrtopodium paniculatum.

We report the first phytochemical study of the neotropical orchid Cyrtopodium paniculatum. Eight new compounds, including one phenanthrene 1, one 9,10-dihydro-phenanthrene 2, one hydroxybenzylphenanthrene 3, two biphenanthrenes 4-5, and three 9,10 dihydrophenanthrofurans 6-8, together with 28 known phenolic compounds, mostly stilbenoids, were isolated from the CH2Cl2 extract of its leaves and pseudobulbs. The structures of the new compounds were established on the basis of extensive spectroscopic methods.

[The Escouflaire Laboratories].

Escouflaire antiasthmatic cigarettes and powders knew certain success during almost one century. The medical use of solanaceae with bronchodilator properties helped relieve numerous asthmatics. The Belgian pharmacist Charles Adolphe Escouflaire (1857-1909), pharmacist from the university of Leuven, Belgium, awarded his diploma in 1879. He created his antiasthmatic products in his pharmacy of Ath and established in 1885 a pharmaceutical laboratory. He registered trademarks under the brand name Zematone for its antiasthmatic cigarettes. His products will be rapidly known and sold all over the world. The discovery of a complete box of medical cigarettes in the Czech Republic allows us to evoke his products, the distributor F. S chnöbling in this country, the modes of display and uses. This article redraws the history of the laboratory under the direction of three generations of the Escouflaire family. The laboratory will expand after WWII with production factories in Baisieux and Blandain before definitely close in 1974.

Purification of vandaterosides from Vanda teres (Orchidaceae) by stepwise gradient centrifugal partition chromatography.

Vandaterosides are polar glucosyloxybenzyl eucomate derivatives found in Vanda teres (Orchidaceae), which display biological activities that slow the skin ageing process. In order to obtain larger quantities to allow us to go further in the bioassays, the hydroalcoholic extract of aerial parts (leaves and stems) of V. teres were fractionated by centrifugal partition chromatography, combining isocratic, gradient, and dual elution modes. The first fractionation was performed on the extract maintained in the stationary phase as water saturated in butanol, while increasing the polarity of the mobile phase by changing the proportions of ethyl acetate/1-butanol/water, in order to obtain two enriched fractions. Vandateroside I was then purified by isocratic mode with ethyl acetate/ethanol/water (46:14:40), while vandateroside II was obtained by combining isocratic elution with ethyl acetate/isopropanol/water (30:20:50) followed by a multiple dual mode with ethyl acetate/ethanol/water (46:14:40). In this manner, hundreds of milligrams of vandateroside I and II were recovered from 10 g of V. teres extract.

Identification of phenanthrene derivatives in Aerides rosea (Orchidaceae) using the combined systems HPLC-ESI-HRMS/MS and HPLC-DAD-MS-SPE-UV-NMR.

INTRODUCTION: In our continued efforts to contribute to the general knowledge on the chemical diversity of orchids, we have decided to focus our investigations on the Aeridinae subtribe. Following our previous phytochemical study of Vanda coerulea, which has led to the identification of phenanthrene derivatives, a closely related species, Aerides rosea Lodd. ex Lindl. & Paxton, was chosen for investigation. OBJECTIVE: To identify new secondary metabolites, and to avoid isolation of those already known, by means of the combined systems HPLC-DAD(diode-array detector) with high-resolution tandem mass spectrometry (HRMS/MS) and HPLC-DAD-MS-SPE(solid-phase extraction)-UV-NMR. METHODS: A dereplication strategy was developed using a HPLC-DAD-HRMS/MS targeted method and applied to fractions from A. rosea stem extract. Characterisation of unknown minor compounds was then performed using the combined HPLC-DAD-MS-SPE-UV-NMR system. RESULTS: The dereplication method allowed the characterisation of four compounds (gigantol, imbricatin, methoxycoelonin and coelonin), previously isolated from Vanda coerulea stem extract. The analyses of two fractions permitted the identification of five additional minor constituents including one phenanthropyran, two phenanthrene and two dihydrophenanthrene derivatives. The full set of NMR data of each compound was obtained from microgram quantities. CONCLUSION: Nine secondary metabolites were characterised in A. rosea stems, utilising HPLC systems combined with high-resolution analytical systems. Two of them are newly described phenanthrene derivatives: aerosanthrene (5-methoxyphenanthrene-2,3,7-triol) and aerosin (3-methoxy-9,10-dihydro-2,5,7-phenanthrenetriol).

[Cosmetic innovations in the Guerlain patents deposited in the XIXth century]. / L'innovation en cosmétique au travers des brevets déposés au XIXe siècle par Guerlain.

The XIXth century was the century of the development of hygiene, cosmetics industry, chemistry and modern pharmacy. After the French revolution, a new legislation establishes a law of recognition of the property of the inventors on their inventions. This paper describes the content of patents and certificates deposited in the XIXth century at the INPI, french national institute of the industrial property, by the creators of Guerlain, a luxury brand of perfumes and cosmetics. This paper allows to discover the variety of the inventions which recovers whitening lotion, soaps, ingenious devices and new perfume substances.

[Marie-Victor Ernest Baudrimont, a famous pharmacist from Compiègne, France]. / Marie-Victor Ernest Baudrimont, pharmacien compiégnois.

Ernest Baudrimont is a pharmacist born in Compiègne in 1821. He is the nephew of the pharmacist chemist Alexandre Baudrimont and is from a family of Compiègne pharmacists. First prize and gold medal in 1846 of the School of Pharmacy in Paris, he obtained in 1852 his Ph D in pharmacy for a dissertation on the formation and composition of mineral waters, and in 1864 is Ph D of physical sciences for a dissertation on the chlorides and bromides of phosphorus. Hospitals Chief Pharmacist in 1854, he had his first position at the Sainte Eugénie children's Hospital, today Trousseau hospital in Paris, position he held until 1875 prior to his appointment as Director of the Paris Civilian Hospitals central Pharmacy. Member of the french Botanical Society, the Society of Medical Hydrology, secretary of the Society of Pharmacy, he was also associate professor of Pharmacy at the School of Pharmacy of Paris. His scientific publications focus on the mineral chemistry i.e he described the nature of white phosphorus; mineral waters and some plants chemistry. One of the major contributions of Ernest Baudrimont was his involvment to the successive editions of the dictionary of the alterations and falsifications of foodstuffs of A. Chevallier. Member of the french Academy of Medicine in 1881, he died in Paris in September 1885.

[Augustin Delondre and Friedrich AuguIst Flückiger : an unpublished correspondence 1868-1869]. / Augustin Delondre et Friedrich August Flückiger : une correspondance inédite 1868-1869.

This article describes an unpublished correspondence between Augustin-Ambroise Delondre (1823- 1879), son of the famous pharmacist Augustin - Pierre Delondre and Friedrich August Flückiger, Swiss pharmacist (1828-1894), professor between 1873 to 1892 of the Chair in pharmacy at the university of Strasbourg and considered as the father of pharmacognosy. This set of 9 unique hand- written letters (1868 and 1869) allows to have an clearer idea of their scientific and human relations.

Arundinosides I-IX and graminifolosides A-B: 2R-benzylmalate and 2R-isobutylmalates derivatives from Arundina graminifolia (D.Don) Hochr. with antioxidant, cytocompatibility and cytoprotective properties.

Phytochemical investigation of the underground parts of Arundina graminifolia D.Don Hochr was conducted leading to the isolation of nine new glucosyloxybenzyl 2R-benzylmalate and two new glucosyloxybenzyl 2R-isobutylmalate derivatives. The compounds were purified using chromatographic techniques and their structures were deduced based on spectroscopic techniques including nuclear magnetic resonance and high-resolution mass spectrometry as well as comparing with previous literature. The antioxidant activities of the isolated compounds were also evaluated. The compounds showed potent antioxidant activities in the ABTS radical scavenging, DPPH radical scavenging and FRAP activities. Furthermore, the isolated compounds were observed to exert minimal cytotoxic effects against RAW 264.7 cell, suggesting biocompatibility as well as cytoprotective effects against hydrogen peroxide induced cell toxicity.

11th Annual LVMH Recherche Symposium: skin rejuvenation.

The 11(th) Annual LVMH Recherche Scientific Symposium was held in London on October 27(th), into the warmth of the distinguished British Library, with nearly 150 industry and research attendees. The meeting organized by LVMH Recherche was centered on the theme of skin rejuvenation. The current state of play for rejuvenation research was summarized, and then advances in the science of skin aging and rejuvenation therapies were discussed in detail. Personalized genomics and current and prospective translational therapies were presented, followed by a clever linking of multiple global theories towards a cohesive plan for future goals in rejuvenation research.

Glucosyloxybenzyl eucomate derivatives from Vanda teres stimulate HaCaT cytochrome c oxidase.

Eucomic acid [(2R)-2-(p-hydroxybenzyl)malic acid)] (1) and three new glucopyranosyloxybenzyl eucomate derivatives, vandaterosides I (2), II (3), and III (4), were isolated and identified from the stems of Vanda teres. Their cellular antiaging properties were evaluated in a human immortalized keratinocyte cell line (HaCaT) by monitoring their effect on cytochrome c oxidase activity, implicated in mitochondrial respiratory function and cellular energy production. Eucomic acid (1) and vandateroside II (3) increased cytochrome c oxidase activity and/or expression, without enhancing cellular mitochondrial content. These two V. teres biomarkers apparently contributed to stimulate respiratory functions in keratinocytes. Since aging and its pathologies may be ascribed to a decline in mitochondrial functions, these biomarkers have the potential to become new natural ingredients for antiaging preparations to remedy age-related disorders such as skin aging.

Endogenous survivin modulates survival and proliferation in UVB-treated human keratinocytes.

Survivin is a bi-functional member of inhibitor of apoptosis protein family, as it is able to both inhibit apoptosis and to regulate cell cycle. We investigated the role of survivin in human keratinocytes under normal conditions and during UVB irradiation. Survivin siRNA decreases proliferation and induces apoptosis in human keratinocytes, in a mode consistent with the mitotic catastrophe. Low doses UVB increase survivin expression at earlier times, while high doses down-regulate survivin level. Low doses UVB induce cell cycle arrest in G2/M, while high doses UVB cause apoptosis. Moreover, overexpression of survivin protects keratinocytes from UVB-induced apoptosis, and silencing of survivin renders keratinocytes more susceptible to UVB-induced cell death. Finally, survivin siRNA increases UVB-induced reduction of cell proliferation. Taken together, these results indicate that survivin plays a critical role in epidermal homeostasis in normal conditions and during UVB exposure, with possible implication in skin carcinogenesis.

Skin aquaporins: function in hydration, wound healing, and skin epidermis homeostasis.

Several aquaporins (AQPs) are expressed in mammalian skin. Some are directly involved in water transport, such as AQP5, which is involved in sweat secretion. In contrast, the physiological role of skin aquaglyceroporins, which permeate both water and glycerol, appears more and more complex. AQP3 is the most abundant skin aquaglyceroporin. Both water and glycerol transport by AQP3 appear to play an important role in hydration of mammalian skin epidermis. In addition, recent data suggest that glycerol transport by AQP3 is involved in the metabolism of lipids in skin as well as in the regulation of proliferation and differentiation of keratinocytes. Finally, AQP3 is also believed to be important in wound healing, as a water channel by facilitating cell migration, and as a glycerol transporter by enhancing keratinocyte proliferation and differentiation.

New glucosyloxybenzyl 2R-benzylmalate derivatives from the undergrounds parts of Arundina graminifolia (Orchidaceae).

Phytochemical investigation of the underground part of the blossoming tropical orchid Arundina graminifolia led to the isolation of six new glucosyloxybenzyl 2R-benzylmalate derivatives named arundinosides L-Q (1-6) together with 5 known compounds arundinosides D-F, J and K (7-11). The structures of the isolated compounds were determined by extensive spectroscopic data analysis. The anti-α-glucosidase and antioxidant activities of the isolated compounds were determined. The result indicated that compounds 4-6 and 9 showed moderate to weak α-glucosidase inhibitory effects as well as moderate antioxidant effect.

The silver locus product (Silv/gp100/Pmel17) as a new tool for the analysis of melanosome transfer in human melanocyte-keratinocyte co-culture.

Melanosomes are melanocyte-specific lysosome-related organelles that are transferred to keratinocytes of the epidermis and anagen hair bulb. Transferred melanin forms supra-nuclear caps that protect epidermal keratinocytes against UV irradiation. The mechanism(s) responsible for melanosome transfer into keratinocytes and their subsequent intra-keratinocyte distribution has long remained one of the most enigmatic of heterotypic cell interactions. Although there have been many attempts to study this process, significant progress has been hindered by the absence of an adequate in vitro model. During our ongoing study of melanocyte-keratinocyte interactions in skin and hair follicle, we have developed a novel in vitro assay that exploits the specificity of Silv/Pmel17/gp100 expression for melanosome/melanin granules. Using matched cultures of keratinocytes and melanocytes isolated from normal healthy epidermis together with double immunofluorescence, we have determined that gp100 is a surprisingly useful tracker of transferred melanin. Moreover, transferred gp100 stained melanin granules emit a bright fluorescence signal, facilitating ready quantification of melanin transfer levels between melanocytes and keratinocytes. This quantitative approach was validated using known inducers and inhibitors of the melanocyte phenotype. This assay further confirmed that cytophagocytosis of melanocyte components (e.g. dendrite tips) by keratinocytes is one route for melanin incorporation into keratinocytes. Lastly, a role for the recently proposed filopodium as a direct conduit for melanin transfer was substantiated using this novel approach. In conclusion, this assay promises to significantly aid our investigations of the molecular basis of melanosome transfer and offers a new tool for the clinical evaluation of melanocyte modulators.

Glycation Damage: A Possible Hub for Major Pathophysiological Disorders and Aging.

Glycation is both a physiological and pathological process which mainly affects proteins, nucleic acids and lipids. Exogenous and endogenous glycation produces deleterious reactions that take place principally in the extracellular matrix environment or within the cell cytosol and organelles. Advanced glycation end product (AGE) formation begins by the non-enzymatic glycation of free amino groups by sugars and aldehydes which leads to a succession of rearrangements of intermediate compounds and ultimately to irreversibly bound products known as AGEs. Epigenetic factors, oxidative stress, UV and nutrition are important causes of the accumulation of chemically and structurally different AGEs with various biological reactivities. Cross-linked proteins, deriving from the glycation process, present both an altered structure and function. Nucleotides and lipids are particularly vulnerable targets which can in turn favor DNA mutation or a decrease in cell membrane integrity and associated biological pathways respectively. In mitochondria, the consequences of glycation can alter bioenergy production. Under physiological conditions, anti-glycation defenses are sufficient, with proteasomes preventing accumulation of glycated proteins, while lipid turnover clears glycated products and nucleotide excision repair removes glycated nucleotides. If this does not occur, glycation damage accumulates, and pathologies may develop. Glycation-induced biological products are known to be mainly associated with aging, neurodegenerative disorders, diabetes and its complications, atherosclerosis, renal failure, immunological changes, retinopathy, skin photoaging, osteoporosis, and progression of some tumors.

Arundinosides A-G, new glucosyloxybenzyl 2R-benzylmalate derivatives from the aerial parts of Arundina graminifolia.

Seven new glucosyloxybenzyl 2R-benzylmalate derivatives, arundinosides A-G (1-7) were isolated from the aerial parts of the bamboo orchid Arundina graminifolia. This is the first occurrence of this class of compounds in the genus Arundina. Their planar structures and absolute configuration were determined by extensive NMR spectroscopic data as well as chemical conversion. Their neuroprotective properties were also evaluated on their potential ability to reduce the beta amyloid damage on PC12 cell model.

Enhancing cell longevity for cosmetic application: a complementary approach.

BACKGROUND AND OBJECTIVES: Cell longevity is linked to sirtuins (silent information regulators), which belong to a family of enzymes implicated in gene silencing, apoptosis, fatty acid metabolism, and regulation of cellular life spans of organisms. Sirtuins are associated with genes that coordinate and optimize the functions of cells as cells struggle to survive in a stressful environment, as it is the case for skin cells. This study focuses on 1) yeast Kluyveromyces biopetides in stimulating the expression of sirtuin in human cutaneous cells and 2) the benefit for the skin of an active skin care product containing yeast Kluyveromyces biopetides. METHODS: Silent mating type information regulation 2 homolog 1 (SIRT1) was investigated by immunostaining, Westem blotting, and cytometry on normal human skin cells in culture and on healthy skin samples ex vivo. SIRT7 are mammalian versions of the yeast SIR2 gene. Cellular integrity and aging was followed by comet assays measuring DNA fragmentation and beta galactosidase activity (a marker of senescence). The test product was yeast Kluyveromyces biopeptides. Thirty-three female subjects aged 37 to 64 years (mean 51.6 years) enrolled in the study. Subjects applied a formulation enriched in 1% of the yeast biopeptides SIRT1 activator once daily to the face and neck for 4 weeks. Dermatologists used a graded scale (1-9) to score fine lines and wrinkles, hydration, pigment color intensity, complexion radiance, skin density, firmness, complexion homogeneity, and texture of the skin before and after the first application and again after 4 weeks of use. A Pixel Skin method, based on an analysis of the gray-level variance and surface of imperfections (age-related parameters) from numerical pictures of the faces, was used to objectively measure the skin care efficacy. RESULTS: The yeast Kluyveromyces biopeptides 1) significantly increased SIRT1 expression in normal human dermal skin fibroblasts in vitro (+172%) and in epidermal cells of healthy human skin ex vivo and 2) decreased cell senescence and DNA fragmentation induced by ultraviolet-B (UVB) stress. At the end of the study, facial improvements could be seen on fine lines and wrinkles, hydration, pigmented spot color intensity, complexion radiance, firmness, complexion homogeneity, and texture. Improvement in hydration was significant immediately after the first application. Skin-pixel measurement and analysis show a significant reduction of the gray variance linked to pixel heterogeneity (-4.2%) and a significant reduction of the surface of skin imperfections (-30.4%). All the indicators from clinical evaluation to the objective measurements of the skin show a significant improvement of the aged skin. CONCLUSION: These results demonstrate the efficacy of the yeast Kluyveromyces biopeptides in activating SIRT 1 of human skin cells, improving their DNA resistance and senescence, and of a formulation enriched in this ingredient in treating multiple skin aging signs.

Hydrating skin by stimulating biosynthesis of aquaporins.

Aquaporins (AQPs) are proteins that facilitate the transport of water across cell membranes. AQP3 expression is related to the expressions of other epidermal proteins involved in water maintenance (ie, CD44, claudin-1, and filaggrin). The expressions of AQP3 water channels are strongly affected by age and chronic sun exposure, and a defective osmotic equilibrium could occur in the epidermis, which would account for the skin dryness observed in older people and skin areas most exposed to sunlight. We investigated active ingredients that are able to increase AQP3 levels in order to improve hydration in human skin keratinocytes. We selected an ethanolic/water (70/30 v/v) extract of Ajuga turkestanica, a plant from Central Asia, as the hydrating agent. After 17 days of treatment every 2 days with this extract (2.5 microg/mL) in vitro, AQP3 expression measured at the protein level in human reconstructed epidermis was significantly increased. Water transport through both aquaporins and aquaglyceroporins and glycerol transport through aquaglyceroporins alone are important to skin hydration. The distribution and the variability of aquaporins in human skin cells suggest that these channels may have important roles in skin physiology. AQPs appear to be key protein targets to improve the resistance and quality of the skin surface as well as to improve aging and sun exposure-induced dryness as shown by their roles in 1) hydrating the living layers of the epidermis where the keratinocyte differentiation takes place and 2) barrier formation and recovery.