Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by SA-β-gal staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.

Preventive Effects of Multi-Lamellar Emulsion on Low Potency Topical Steroid Induced Local Adverse Effect

BACKGROUND: Topical steroid treatment induces diverse local Wand systemic adverse effects. Several approaches have been tried to reduce the steroid-induced adverse effects. Simultaneous application of physiological lipid mixture is also suggested. OBJECTIVE: Novel vehicles for topical glucocorticoids formulation were evaluated for the efficacy of reducing side-effects and the drug delivery properties of desonide, a low potency topical steroid. METHODS: Transcutaneous permeation and skin residual amount of desonide were measured using Franz diffusion cells. The in vivo anti-inflammatory activity was evaluated using murine model. RESULTS: Topical steroids formulation containing desonide, in either cream or lotion form, were prepared using multi-lamellar emulsion (MLE), and conventional desonide formulations were employed for comparison. MLE formulations did not affect the anti-inflammatory activity of the desonide in phobol ester-induced skin inflammation model, compared with conventional formulations. While the penetrated amounts of desonide were similar for all the tested formulations at 24 hours after application, the increased lag time was observed for the MLE formulations. Interestingly, residual amount of desonide in epidermis was significantly higher in lotion type MLE formulation. Steroid-induced adverse effects, including permeability barrier function impairment, were partially prevented by MLE formulation. CONCLUSION: Topical desonide formulation using MLE as a vehicle showed a better drug delivery with increased epidermal retention. MLE also partially prevented the steroid-induced side effects, such as skin barrier impairment.

Effectiveness of Topical Chia Seed Oil on Pruritus of End-stage Renal Disease (ESRD) Patients and Healthy Volunteers

BACKGROUND: Several studies have been performed to evaluate the efficacy of dietary n-3 fatty acid for patients with renal dysfunction. While about 40% to 80% of patients with end-stage renal disease (ESRD) complain about pruritus and xerosis, there are few reports on the effects of topical n-3 fatty acid on these symptoms. OBJECTIVE: In order to investigate the possible beneficial effects of topical n-3 fatty acid, oils extracted from chia (Salvia hispanica) seed were formulated into topical products, the effects of which were measured. METHODS: Five healthy volunteers having xerotic pruritus symptoms and 5 patients with pruritus caused by either ESRD or diabetes were involved in this study. A topical formulation containing 4% chia seed oils were applied for an 8-week duration. Subjective itching symptoms were assessed on a 6-point scale, as were other skin functions, namely transepidermal water loss and skin capacitance. RESULTS: After the 8 weeks of application, significant improvements in skin hydration, lichen simplex chronicus, and prurigo nodularis were observed in all patients. A similar improvement was also observed among healthy volunteers with xerotic pruritus. Improvement of epidermal permeability barrier function and skin hydration, represented by trans-epidermal water loss and skin capacitance, respectively, were also observed. No adverse effects were observed in all the tested patients and volunteers. CONCLUSION: Chia seed oil can be used as an adjuvant moisturizing agent for pruritic skin, including that of ESRD patients.

The Clinical Efficacy of a Multi-Lamellar Emulsion Containing Pseudoceramide in Childhood Atopic Dermatitis: An Open Crossover Study

BACKGROUND: The abnormal barrier function in atopic dermatitis(AD) is caused by a reduction in the amounts of ceramides in the intercellular lipids in the stratum corneum(SC). Replenishing the SC via the topical application of ceramides and pseudoceramides leads to effective recovery of the barrier function of skin. OBJECTIVES: An open clinical crossover evaluation was conducted to investigate the effects in AD of a multi-lamellar emulsion(MLE) that contained pseudoceramide(PC-9s). METHODS: The study group included 30 AD patiendaverage age: 4.4 yr, range: 1-8 yr), who applied MLE or a commercial moisturizing cream(CMC, 5% urea) alternately for four weeks each. We divided the subjects into two subgroups and started with different treatments in each subgroup. Treatment efficacy was evaluated using the average subjective satisfaction scores for each symptom and the global clinical response. In addition, the SCORAD(Scoring AD) index was adopted to evaluate the severity of AD as objectively as possible. The patients were evaluated using this index every other week. RESULTS: Although the SCORAD improved in both subgroups, the patients had better results (p<0.05) when applying MLE(31-35% decrease) than CMC(13% increase to 14% decrease). The subjective satisfaction scores of the symptoms and signs of patients, including itching, erythema, and dry skin, were higher in the MLE group than in the CMC group, and the global response to treatment was also better in the MLE group. During the follow-up period, AD improved in all patients. MLE was more effective than CMC in our patients. CONCLUSIONS: The topical application of a multi-lamellar emulsion containing pseudoceramide is an effective regimen for improving symptoms of AD.