Acetyl zingerone: An efficacious multifunctional ingredient for continued protection against ongoing DNA damage in melanocytes after sun exposure ends.

OBJECTIVE: Recent research has shown that significant levels of cyclobutane pyrimidine dimers (CPDs) in DNA continue to form in melanocytes for several hours in the dark after exposure to ultraviolet radiation (UVR) ends. We document the utility of a new multifunctional ingredient, 3-(4-hydroxy, 3-methoxybenzyl)-pentane-2,4-dione (INCI acetyl zingerone (AZ)), to protect melanocytes against CPD formation after UVR exposure ends. METHODS: The use of AZ as an intervention to reduce CPD formation after irradiation was assessed in vitro by comparing kinetic profiles of CPD formation for several hours after irradiation in cells that were untreated or treated with AZ immediately after irradiation. Multifunctional performance of AZ as an antioxidant, quencher and scavenger was established using industry-standard in vitro chemical assays, and then, its efficacy in a more biological assay was confirmed by its in vitro ability to reduce intracellular levels of reactive oxygen species (ROS) in keratinocytes exposed to UVA radiation. Molecular photostability was assessed in solution during exposure to solar-simulated UVR and compared with the conventional antioxidant α-tocopherol. RESULTS: Even when added immediately after irradiation, AZ significantly inhibited ongoing formation of CPDs in melanocytes after exposure to UVA. Incubation with AZ before irradiation decreased intracellular levels of UVA-induced ROS formation in keratinocytes. Compared with α-tocopherol, the molecular structure of AZ endows it with significantly better photostability and efficacy to neutralize free radicals (∙OH, ∙OOH), physically quench singlet oxygen (1 O2 ) and scavenge peroxynitrite (ONOO- ). CONCLUSION: These results designate AZ as a new type of multifunctional ingredient with strong potential to extend photoprotection of traditional sunscreens and daily skincare products over the first few hours after sun exposure ends.

OBJECTIF: Une étude récente a montré que des taux significatifs de dimères cyclobutyliques de pyrimidine (Cyclobutane Pyrimidine Dimers, CPD) dans l'ADN continuaient à se former dans les mélanocytes pendant plusieurs heures, dans l'obscurité, après que leur exposition aux radiations ultraviolettes (UV) ait pris fin. Nous documentons l'utilité d'un nouvel ingrédient multifonctionnel, le 3-(4-hydroxy, 3- méthoxybenzyle)-pentane-2,4-dione (INCI acétyle zingérone (AZ)), pour protéger les mélanocytes contre la formation de CPD une fois l'exposition aux rayonnements UV terminée. MÉTHODES: L'utilisation d'AZ en tant qu'intervention pour réduire la formation de CPD après exposition aux ultraviolets a été évaluée in vitro en comparant les profils cinétiques de la formation de CPD pendant plusieurs heures après irradiation dans des cellules non traitées et dans des cellules traitées à l'AZ immédiatement après exposition. La performance multifonctionnelle de l'AZ comme agent antioxydant, absorbant et éliminateur a été établie à l'aide de dosages chimiques in vitro standard pour l'industrie, après quoi son efficacité à un dosage plus biologique a été confirmée par sa capacité in vitro à réduire les taux intracellulaires d'espèces réactives de l'oxygène (ROS) dans les kératinocytes exposés au rayonnement UV. La photostabilité moléculaire a été évaluée en solution pendant l'exposition UV simulée de rayonnements solaire et par rapport au traitement antioxydant conventionnel α-tocophérol. RÉSULTATS: Même lorsqu'il a été ajouté immédiatement après exposition, l'AZ a inhibé la formation continue de CPD dans les mélanocytes après l'exposition aux UV et ce de façon significative. Une incubation avec de l'AZ avant exposition a entraîné une diminution des taux intracellulaires de formation des ROS, induits par le rayonnement UV, dans les kératinocytes. Par rapport au α-tocophérol, la structure moléculaire de l'AZ lui confère une photostabilité significativement meilleure ainsi qu'une plus grande efficacité pour neutraliser les radicaux libres (∙OH, ∙OOH), absorber physiquement l'oxygène singulet (1 O2 ) et éliminer le peroxynitrite (ONOO- ). CONCLUSION: Ces résultats montrent que l'AZ, considéré comme un ingrédient multifonctionnel d'un type nouveau, jouit d'un fort potentiel de prolongation de l'effet photoprotecteur des écrans solaires traditionnels et des produits de soins de la peau pendant quelques heures après la fin de l'exposition au soleil.

Improvement of hydration and epidermal barrier function in human skin by a novel compound isosorbide dicaprylate.

OBJECTIVE: The study involved the synthesis of a novel derivative of caprylic acid - isosorbide dicaprylate (IDC) - and the evaluation of its potential in improving water homoeostasis and epidermal barrier function in human skin. METHODS: The effect of IDC on gene expression was assayed in skin organotypic cultures by DNA microarrays. The results were then confirmed for a few key genes by quantitative PCR, immuno- and cytochemistry. Final validation of skin hydration properties was obtained by four separate clinical studies. Level of hydration was measured by corneometer either by using 2% IDC lotion alone vs placebo or in combination with 2% glycerol lotion vs 2% glycerol only. A direct comparison in skin hydration between 2% IDC and 2% glycerol lotions was also carried out. The epidermal barrier function improvement was assessed by determining changes in transepidermal water loss (TEWL) on the arms before and after treatment with 2% IDC lotion versus placebo. RESULTS: IDC was found to upregulate the expression of AQP3, CD44 and proteins involved in keratinocyte differentiation as well as the formation and function of stratum corneum. A direct comparison between 2% IDC versus 2% glycerol lotions revealed a three-fold advantage of IDC in providing skin hydration. Severely dry skin treated with 2% IDC in combination with 2% glycerol showed 133% improvement, whereas 35% improvement was observed with moderately dry human skin. CONCLUSION: Topical isosorbide dicaprylate favourably modulates genes involved in the maintenance of skin structure and function, resulting in superior clinical outcomes. By improving skin hydration and epidermal permeability barrier, it offers therapeutic applications in skin ageing.

3-(3,4,5-Trimethoxybenzylidene)-2,4-pentanedione: Design of a novel photostabilizer with in vivo SPF boosting properties and its use in developing broad-spectrum sunscreen formulations.

OBJECTIVE: The study concerned the synthesis of a novel photostabilizer based on benzylidenepentanedione chemistry and the evaluation of its potential in developing a broad-spectrum sunscreen formulation containing avobenzone. METHODS: 3-(3,4,5-Trimethoxybenzylidene)-2-4-pentanedione (TMBP) was synthesized through a condensation reaction and incorporated into a sunscreen formulation containing, inter alia, avobenzone. The SPF, critical wavelength and in vitro photostability of the product were measured. The photostability was compared with that afforded by current avobenzone photostabilizers, namely octocrylene, ethylhexylmethoxycrylene and diethylhexylsyringylidenemalonate. The photostability of TMBP either alone or in the presence of avobenzone in a methanolic solution was also evaluated by UV spectrophotometric and HPLC analyses. The optical properties of TMBP were estimated experimentally and supported by time-dependent density functional theory (TD-DFT) calculations. RESULTS: The ability of TMBP to stabilize avobenzone under ultraviolet (UV) light exposure was shown both in formulated products and in solution. A comparative stability study incorporating various combinations of avobenzone, TMBP (vs. three commercial photostabilizers) and UVB sunscreens clearly showed TMBP to be a very effective stabilizer. The photostabilizing effect of TMBP arises from triplet-state energy transfer from avobenzone to TMBP and through light-induced reactions that preserve the main chromophores. Interestingly, a 50% in vivo SPF boosting was observed when TMBP was used with organic and inorganic sunscreens when alone it has no contribution to SPF. TMBP-containing sunscreen formulations clearly showed a critical wavelength of well over 370 nm and can thus be categorized as broad-spectrum sunscreens. CONCLUSION: We were able to design a very effective photostabilizer, trimethoxybenzylidene pentanedione (INCI name), based on benzylidenepentanedione chemistry. TMBP is very efficient in stabilizing avobenzone in formulated products and boosts in vivo SPF by >50% for organic and inorganic sunscreens, and the formulations have critical wavelengths of >370 nm. These efficacious properties make it a promising additive for inclusion in broad-spectrum photoprotective products.

Bakuchiol: a retinol-like functional compound revealed by gene expression profiling and clinically proven to have anti-aging effects.

OBJECTIVE: The study was undertaken to compare the skin care related activities of retinol and bakuchiol, a potential alternative to retinoids. Retinol is a pivotal regulator of differentiation and growth of developing as well as adult skin. Retinoic acid is the major physiologically active metabolite of retinol regulating gene expression through retinoic acid receptor - dependant and independent pathways. METHODS: Comparative gene expression profiling of both substances in the EpiDerm FT full thickness skin substitute model was undertaken. Furthermore, type I, III and IV collagen, as well as aquaporin 3 expression was analyzed by ELISA and/or histochemistry in human dermal fibroblasts and/or Epiderm FT skin substitutes. RESULTS: Bakuchiol is a meroterpene phenol abundant in seeds and leaves of the plant Psoralea corylifolia. We present evidence that bakuchiol, having no structural resemblance to retinoids, can function as a functional analogue of retinol. Volcano plots showed great overall similarity of retinol and bakuchiol effects on the gene expression profile. This similarity was confirmed by the side-by-side comparison of the modulation of individual genes, as well as on the protein level by ELISA and histochemistry. Retinol-like functionality was further confirmed for the upregulation of types I and IV collagen in DNA microarray study and also show stimulation of type III collagen in the mature fibroblast model. Bakuchiol was also formulated into a finished skin care product and was tested in clinical case study by twice-a-day facial application. The results showed that, after 12 weeks treatment, significant improvement in lines and wrinkles, pigmentation, elasticity, firmness and overall reduction in photo-damage was observed, without usual retinol therapy-associated undesirable effects. CONCLUSION: Based on these data, we propose that bakuchiol can function as an anti-ageing compound through retinol-like regulation of gene expression.

A comparative study of contrast dacryocystogram and nuclear dacryocystogram.

A comparative study was run between conventional radiographic contrast dacryocystogram and radioisotope scan of the lacrimal drainage apparatus (henceforth called "nuclear dacryocystogram"). A total of 20 contrast dacryocystograms (DCG), 22 irrigations, and 42 nuclear dacryocystograms (DCG) were performed in 21 patients having symptoms of obstruction in the lacrimal drainage system. The study revealed that there was a good correlation between these two diagnostic techniques and nuclear DCG was, perhaps, superior to contrast DCG.

Selective demethylation of polymethoxyxanthones with aqueous piperidine.

Data are presented for selective demethylation of eight polymethoxyxanthones with aqueous piperdine. Clarification and rationalization of the present and previous observations are made. The mechanism is defined in terms of both resonance effects and steric factors.

Chemical constituents of Gentianaceae XXIV: Anti-Mycobacterium tuberculosis activity of naturally occurring xanthones and synthetic analogs.

Anti-Mycobacterium tuberculosis H37 RV data are presented for the individual xanthones of Canscora decussata Schult and Swertia purpurascens Wall (Gentianaceae); a few, from the former species, showed significant activity. Additionally, sturcture--activity relationships of these compounds are evaluated on the basis of the minimum inhibitory concentration data of 18 naturally occurring xanthones bearing 1,3,5- 1,3,5,6-, 1,3,6,7-, 1,3,5,8-, 1,3,5,6,7-, and 1,3.6,7,8-oxygenated patterns and six synthetic analogs.

Chemical constituents of genianaceae XX: natural occurrence of (-)-loliolide in Canscora decussata.

Loliolide was isolated as a native compound from Canscora decussata Schult (Gentianaceae). Physical and spectral (UV, IR, PMR, CMR, and mass spectra) properties of the compound and its acetate derivative established its identity. The significance of the cooccurrence of loliolide with a number of carotenoids in C. decussata and the facile transformation of violaxanthin into loliolide and violoxin are discussed in the light of the biogenesis of the degraded carotenoid.

Chemical constituents of gentianaceae XIV: tetraoxygenated and pentaoxygenated xanthones of Swertia purpurascens Wall.

The whole plant of Swertia purpurascens Wall. (Gentianaceae) has been shown to contain five tetraoxygenated and three pentaoxygenated zanthones. These are identified as 1,5,8-trihydroxy-3-methoxyxanthone, 1,3,8-trihydroxy-5-methoxyzanthone, 1-hydroxy-3,7,8-trimethoxyxanthone, 1,3,7,8-tetrahydroxyxanthone, 1,3,5,8-tetrahydroxyxanthone, and 1-hydroxy-3,4,7,8-tetramethoxyxanthone by chemical and spectral evidence. Additionally, the crude mixture of natural xanthones has been shown to include two partially emthylated pentaoxygenated xanthones as minor entities, which yield 1-hydroxy-3,4,7,8-tetramethoxyxanthone and 1-hydroxy-3,4,5,8-tetramethoxyxanthone on methylation. This is the first time that pentaoxygenated xanthones have been found in a member of the genus Swertia. 1-Hydroxy-3,4,7,8-tetramethoxyxanthone was previously known only as a synthetic compound. The total xanthones of S. purpurascens produce significant CNS stimulant actions, consistent with some therapeutic uses of the plant extract in the Indian system of medicine. The chemotaxonomic significance of the cooccurrence of various biogenetically related chemical characters in a single plant species is appraised.

Antimicrobial activity of Eupatorium ayapana.

Petroleum ether and methanolic extracts of leaves of Eupatorium ayapana were tested for their antimicrobial activity. The petroleum ether extract showed higher antibacterial and antifungal activity than the methanolic extract.