Folic acid and creatine improve the firmness of human skin in vivo

Background The decrease in firmness is a hallmark of skin aging. Accelerated by chronic sun exposure, fundamental changes occur within the dermal extracellular matrix over the years, mainly impairing the collagenous network. Aims Based on the qualitative and quantitative assessment of skin firmness, in vitro and in vivo studies were carried out to elucidate the effects of topical folic acid and creatine to counteract this age‐dependent reduction in the amount of collagen. Patients/Methods Topical application of a commercially available formulation containing folic acid and creatine was performed to study effects on skin firmness in vivo using cutometric analysis. Imaging and quantification of collagen density were carried out using multiphoton laser scanning microscopy (MPLSM). To investigate the effects of these compounds on collagen gene expression, procollagen synthesis, and collagen fibril organization, complementary in vitro studies on cultured fibroblast‐populated collagen gels were carried out. Results The underlying structural changes in the collagen network of young and aged sun‐exposed facial skin in vivo were visualized by MPLSM. Topical application of a folic acid‐ and creatine‐containing formulation significantly improved firmness of mature skin in vivo. Treatment of fibroblast‐populated dermal equivalents with folic acid and creatine increased collagen gene expression and procollagen levels and improved collagen fiber density, suggesting that the in vivo effects are based on the overall improvement of the collagen metabolism. Conclusions Employing MPLSM, dermal changes occurring in photo‐aged human skin were visualized in an unprecedented manner and correlated to a loss of firmness. Treatment of aged skin with a topical formulation containing folic acid and creatine counteracted this age‐dependent decline by exerting sustained effects on collagen metabolism. Our results support previous findings on the efficacy of these actives.     

Dermal penetration of creatine from a face-care formulation containing creatine, guarana and glycerol is linked to effective antiwrinkle and antisagging efficacy in male subjects

Background The dermal extracellular matrix provides stability and structure to the skin. With increasing age, however, its major component collagen is subject to degeneration, resulting in a gradual decline in skin elasticity and progression of wrinkle formation. Previous studies suggest that the reduction in cellular energy contributes to the diminished synthesis of cutaneous collagen during aging. Aims To investigate the potential of topically applied creatine to improve the clinical signs of skin aging by stimulating dermal collagen synthesis in vitro and in vivo. Patients/Methods Penetration experiments were performed with a pig skin ex vivo model. Effects of creatine on dermal collagen gene expression and procollagen synthesis were studied in vitro using cultured fibroblast‐populated collagen gels. In a single‐center, controlled study, 43 male Caucasians applied a face‐care formulation containing creatine, guarana extract, and glycerol to determine its influence on facial topometric features. Results Cultured human dermal fibroblasts supplemented with creatine displayed a stimulation of collagen synthesis relative to untreated control cells both on the gene expression and at the protein level. In skin penetration experiments, topically applied creatine rapidly reached the dermis. In addition, topical in vivo application of a creatine‐containing formulation for 6 weeks significantly reduced the sagging cheek intensity in the jowl area as compared to baseline. This result was confirmed by clinical live scoring, which also demonstrated a significant reduction in crow’s feet wrinkles and wrinkles under the eyes. Conclusions In summary, creatine represents a beneficial active ingredient for topical use in the prevention and treatment of human skin aging.     

Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV‐B irradiation

Please cite this paper as: Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV‐B irradiation. Experimental Dermatology 2010; 19 : e182–e190. Abstract: Ellagic acid, a polyphenol compound present in berries and pomegranate, has received attention as an agent that may have potential bioactivities preventing chronic diseases. This study examined photoprotective effects of ellagic acid on collagen breakdown and inflammatory responses in UV (ultraviolet)‐B irradiated human skin cells and hairless mice. Ellagic acid attenuated the UV‐B‐induced toxicity of HaCaT keratinocytes and human dermal fibroblasts. Non‐toxic ellagic acid markedly prevented collagen degradation by blocking matrix metalloproteinase production in UV‐B‐exposed fibroblasts. Anti‐wrinkle activity of ellagic acid was further investigated in hairless mice exposed to UV‐B, in which it attenuated UV‐B‐triggered skin wrinkle formation and epidermal thickening. Topical application of 10 μmol/l ellagic acid diminished production of pro‐inflammatory cytokines IL‐1β and IL‐6, and blocked infiltration of inflammatory macrophages in the integuments of SKH‐1 hairless mice exposed to UV‐B for 8 weeks. In addition, this compound mitigated inflammatory intracellular cell adhesion molecule‐1 expression in UV‐B‐irradiated keratinocytes and photoaged mouse epidermis. These results demonstrate that ellagic acid prevented collagen destruction and inflammatory responses caused by UV‐B. Therefore, dietary and pharmacological interventions with berries rich in ellagic acid may be promising treatment strategies interrupting skin wrinkle and inflammation associated with chronic UV exposure leading to photoageing.     

Three clinical studies showing the anti-aging benefits of sodium salicylate in human skin

Background Anti‐aging effects of high concentrations of salicylic acid (SA) peels are commonly known. Like all acids, SA can produce somatosensory and visible irritation to the skin and as such may be unsuitable for subjects with sensitive skin. Aims To provide evidence that sodium salicylate (SS) obtained from neutralization of 1% SA by sodium hydroxide can deliver significant anti‐aging benefits. Methods The effects of SS were examined using three approaches: (1) evaluating its effects on stimulating the synthesis of fibrillin and collagen‐1 in vivo; (2) examining its efficacy by using Fast Optical in vivo Topometry (FOITS) in a double‐blind, placebo‐controlled clinical study; (3) determining its effects on both expert and naïve grader assessement of wrinkles in a double‐blind, placebo‐controlled study. Results In the first study SS produced significant increases of the fibrillin and collagen‐1 anti‐aging biomarkers compared with the untreated skin control. A commercially available retinol cream delivered similar effects to SS. In the second study using FOITS we showed that the SS formulation significantly reduced wrinkle depth (Rz) and skin roughness (Ra) after 4 and 8 weeks of daily application vs. placebo (Rz: ?8.2 ± 1.40% and ?11.4 ± 1.07%; Ra: ?7.8 ± 1.33% and ?11.9 ± 0.61%; P < 0.01). In the third study reductions in wrinkle depth were observed by expert assessment at both 4 and 8 weeks for the SS‐containing formulation compared to its placebo (P < 0.05). Equally, non‐expert graders recorded the SS formulation superior to its placebo. Conclusion Although the mechanism of action is not completely understood, we believe the benefits of SS are derived from its intrinsic stratum corneum exfoliation effects. All three studies demonstrate the significant anti‐aging effects of SS that are especially suitable for subjects with sensitive skin.     

Heparanase activation induces epidermal hyperplasia,angiogenesis, lymphangiogenesis and wrinkles

Please cite this paper as: Heparanase activation induces epidermal hyperplasia, angiogenesis, lymphangiogenesis and wrinkles. Experimental Dermatology 2010; 19 : 965–972. Abstract: To clarify the difference between cutaneous responses to single and repeated barrier disruption, changes of epidermal gene expression were examined by using RT‐PCR. In repeatedly barrier‐disrupted skin, heparanase was specifically up‐regulated in epidermis. In addition, there was a marked decrease in heparan sulfate (HS) chains of perlecan in basement membrane at the dermal–epidermal junction (DEJ) compared with singly disrupted skin. HS chains form a reservoir for heparan sulfate‐binding growth factors. In repeatedly barrier‐disrupted skin, expression of vascular endothelial growth factor‐A (VEGF‐A), an angiogenic factor, was induced in epidermis, whereas thrombospondin‐1 (TSP‐1), an angiogenesis inhibitor, was down‐regulated, and concomitantly blood vessels were elongated and enlarged in dermis. Expression of VEGF‐C, a lymphangiogenesis factor, was augmented in epidermis of repeatedly barrier‐disrupted skin, concomitantly with an increase in the number and size of lymphatic vessels. Topical application of a synthetic heparanase inhibitor, 1‐[4‐(1H‐benzoimidazol‐2‐yl)phenyl]‐3‐[4‐(1H‐benzoimidazol‐2‐yl)phenyl]urea, to skin after barrier disruption significantly suppressed wrinkle formation, degradation of HS chains in the basement membrane, epidermal hyperplasia and the changes of blood and lymphatic vessels. These results suggest that chronic barrier disruption activates heparanase and induces gene expression changes, leading to increased growth factor interaction between epidermis and dermis, and facilitating various cutaneous changes, including wrinkle formation.     

Natural Arctium lappa fruit extract improves the clinical signs of aging skin

Background Subclinical, chronic tissue inflammation involving the generation of cytokines (e.g., interleukin‐6 and tumor necrosis factor‐alpha) might contribute to the cutaneous aging process. Aims This study aims to screen for an active ingredient with anti‐inflammatory (i.e., reduction of interleukin‐6 and tumor necrosis factor‐alpha) and matrix‐stimulating efficacy which improves the clinical signs of skin aging in vivo. Patients/methods In vitro studies with pure Arctiin were performed investigating the inhibition of cytokine induction and stimulation of collagen neosynthesis. In vivo home‐in‐use studies using an Arctium lappa fruit extract–containing formulation were carried out to determine procollagen and hyaluronan synthesis, hyaluronan synthase‐2 gene expression, and reduction of wrinkle volume after treatment. Results In vitro studies on human dermal fibroblasts and monocyte‐derived dendritic cells supplemented with pure Arctiin showed relative to untreated control cells a stimulation of collagen synthesis and a decrease in interleukin‐6 and tumor necrosis factor‐alpha concentration, respectively. In addition, topical in vivo application of an A. lappa fruit extract–containing formulation for 12 weeks significantly stimulated procollagen synthesis and increased hyaluronan synthase‐2 expression as well as hyaluronan levels compared to vehicle‐treated control areas. Similarly, after a 4‐week treatment with an A. lappa fruit extract–containing formulation, wrinkle volume in the crow's feet area was significantly reduced as compared to treatment with the vehicle. Conclusions Our data show that topical treatment with a natural A. lappa fruit extract significantly improves the metabolism of the dermal extracellular matrix and leads to a visible wrinkle reduction in vivo. In conclusion, A. lappa fruit extract represents a targeted means to regenerate dermal structures and, thus, offers an effective treatment option for mature skin.     

Improvement in skin wrinkles from the use of photostable retinyl retinoate: a randomized controlled trial

Background Photoaged skin can be treated with retinoids, which are natural and synthetic vitamin A derivatives. However, these are photounstable and can cause skin irritation, which is a major limitation in their use in general cosmetics. Retinyl retinoate, which is an ester of all‐trans retinoic acid (RA) and all‐trans retinol, has reduced toxicity due to blocking of the carboxyl end group of RA and higher skin regeneration activity than retinol. Objectives To assess the efficacy of a photostable retinyl retinoate in treating women over 30 years old with periorbital wrinkles. Methods We conducted two clinical studies with a total of 46 Korean women with periorbital wrinkles, who were not pregnant, nursing or undergoing any concurrent therapy. In the first clinical study, the efficacy of retinyl retinoate was compared with placebo. Twenty‐four patients completed a 12‐week trial of 0·06% retinyl retinoate applied twice daily to one side of the face and a placebo applied to the other side. In the second clinical study, the efficacy of retinyl retinoate was compared with retinol. Twenty‐two patients completed an 8‐week trial of 0·06% retinyl retinoate applied twice daily to one side of the face and 0·075% retinol applied to the other side. Efficacy was based on a global photodamage score, photographs, and image analysis using replicas and visiometer analysis (Skin‐Visiometer SV 600; Courage & Khazaka, Cologne, Germany) every 4 weeks. The standard wrinkle and roughness parameters used in assessing skin by visiometer were calculated and statistically analysed. Results The retinyl retinoate‐treated wrinkles improved compared with wrinkles treated with placebo or retinol, as assessed by both the investigators and the subjects. Also, skin replica analysis indicated significant improvements in retinyl retinoate‐treated skin in both studies, especially in average roughness. Conclusions Retinyl retinoate applied twice daily was significantly more effective than a placebo or retinol in treating periorbital wrinkles. Importantly, no severe side‐effects were observed.     

Serum amyloid A1 secreted from UV‐irradiated keratinocytes induces matrix metalloproteinase‐1 in fibroblasts through toll‐like receptor 4

Ultraviolet (UV) irradiation on skin triggers photoageing‐related phenotypes such as formation of wrinkles. UV ray upregulates matrix metalloproteinase‐1 (MMP‐1), which in turn degrades extracellular matrix proteins, mostly collagens. Serum amyloid A1 (SAA1) is an acute‐phase protein of which plasma concentration increases in response to inflammation. Although the expression of SAA1 in the skin was reported, its function in the skin is yet to be studied. In this research, we found that the expression of SAA1 was increased in acute UV‐irradiated buttock skin and photoaged forearm skin in vivo. UV irradiation also increased SAA1 in normal human epidermal keratinocytes (NHEK), and treatment of recombinant human SAA1 (rhSAA1) induced MMP‐1 in normal human dermal fibroblasts (NHDF) but not in NHEK. Next, we demonstrated that NHDF treated with UV‐irradiated keratinocyte‐conditioned media showed the increased MMP‐1 expression; however, this increase of MMP‐1 in NHDF was inhibited by knockdown of SAA1 in NHEK. In addition, knockdown of Toll‐like receptor 4 (TLR4) inhibited rhSAA1‐induced MMP‐1 expression in NHDF. Taken together, our data showed that UV‐induced SAA1 production in NHEK, and this secreted SAA1 induced MMP‐1 expression in NHDF in a paracrine manner through TLR4 signalling pathway. Therefore, our results suggest that SAA1 can be a potential mediator for UV‐induced MMP‐1 expression in human skin.     

ULTRASTRUCTURAL STUDY OF HYALURONIC ACID BEFORE AND AFTER THE USE OF A PULSED ELECTROMAGNETIC FIELD, ELECTRORYDESIS, IN THE TREATMENT OF WRINKLES

Background. Treatment of wrinkles has become an increasing problem for dermatologists. Hyaluronic acid is a component of the family of glycosaminoglycans (GAGS, substances known for their property of retaining water), that significantly decreases with aging and in wrinkles. A new technique that uses a specific pulsed electromagnetic field, electrorydesis, has been introduced in the treatment of wrinkles associated with aging. The treatment is based on the reported in vitro effects of specific electromagnetic fields on fibroblast cultures (e.g., an increase in DNA synthesis and in the production of collagen and presumably also of GAGS). Methods. The in vivo effects of the electromagnetic field on aged skin (3 subjects aged 50, 56 and 60 years), with particular focus on the ultrastructural modifications and GAGS amount before and after the treatment, were evaluated by electron microscope. Results. The ultrastructural study (tissue stained with al-cian blue) showed after treatment a significant increase (p < 0.005) of the electron-dense granules (corresponding to hyaluronic acid), located in collagen elastic fibers, and in the soluble matrix. This presumably leads to subsequent edema that was clinically evident after the treatment. Conclusions. These data suggest that the increased levels of GAGS and the subsequent edema of the dermis could explain at least in part the clinical changes observed after electrorydesis treatment (e.g., swelling and “disappearance” of the wrinkle).     

Improvement in skin wrinkles using a preparation containing human growth factors and hyaluronic acid serum

Background: Skin aging is accompanied by wrinkle formation. At some sites, such as the periorbital skin, this is a relatively early phenomenon. Objective: We evaluated the anti-wrinkle effect of a preparation containing human growth factor and hyaluronic acid serum on periorbital wrinkles (crow's feet). Materials and methods: In total, 23 Korean women (age range: 39–59 years), who were not pregnant, nursing, or undergoing any concurrent therapy, were enrolled in this study. All the patients completed an 8-week trial of twice-daily application of human growth factor and hyaluronic acid serum on the entire face. Efficacy was based on a global photodamage score, photographs, and image analysis using replicas and visiometer analysis every 4 weeks. The standard wrinkle and roughness parameters used in assessing skin by visiometer were calculated and statistically analyzed. Results: Periorbital wrinkles were significantly improved after treatment, with improvements noted both by physician's assessment and visiometer analysis. Conclusion: Topical application of human growth factor and hyaluronic acid was beneficial in reducing periorbital wrinkles.     

Efficacy of anti-aging products for periorbital wrinkles as measured by 3-D imaging

Background The periorbital area is a key wrinkle‐prone region, where the first signs of aging usually appear. Aims To demonstrate the ability of new anti‐aging moisturizing products to improve overall smoothness and wrinkle depth appearance in the periorbital region via the Fast Optical in vivo Topometry of Human Skin (FOITS). Methods Two double‐blind, randomized, controlled, split‐face studies (n = 42, Study 1; n = 35, Study 2) were conducted in women 30–70 years old with moderate to distinct periorbital wrinkles. Subjects applied 0.5 g of individual products to half their face twice daily for 4 weeks. Four test products containing niacinamide, the peptides Pal‐KT and Pal‐KTTKS, and carnosine were used and included a daytime SPF 30 lotion also containing antioxidants, a night cream, an eye cream also containing caffeine, and a wrinkle treatment containing retinyl propionate. The wrinkle treatment was only tested in Study 2. The FOITS technique was used to measure changes in periorbital R_a (mean roughness) and R_z (average maximum roughness) at 2 and 4 weeks. Results In Study 1, the daytime SPF 30 lotion, night cream, and eye cream significantly improved crow’s feet smoothness after 4 weeks relative to no treatment. After 4 weeks, the daytime SPF 30 lotion and night cream, but not the eye cream, were significantly better than no treatment at improving R_z. In Study 2, the night cream, eye cream, and wrinkle treatment, but not the daytime SPF 30 lotion, significantly improved both R_a and R_z after 4 weeks. To increase power and precision of estimates, a meta‐analysis was performed; the pooled data showed all three products were significantly better than no treatment at improving R_a and R_z after 4 weeks. Conclusions Four weeks of treatment with these products was shown to improve the smoothness of periorbital skin and to reduce the apparent depth of larger wrinkles.     

The effect of Zanthoxylum bungeanum maxim extract on crow's feet: A double‐blind,split‐face trial

As one of the most obvious signs of aging, wrinkles have long been the concern of many people and continue to be a major topic in dermal‐cosmetic industry. Accordingly, there is a need to develop products with good efficacy and safety profile. The Zanthoxylum bungeanum maxim (ZBM) extract is a natural food which may possess the property of a toxin‐like botulinum. To evaluate the efficacy and safety of a formulation that contains 2% ZBM pericarp extract in the treatment of wrinkles. Twenty females aged 35–60 years old were enrolled in this randomized, vehicle‐controlled, double‐blind, and split‐face trial. The trial lasted for 30 days, when participants randomly used formulations containing 2% ZBM extract on one side of the temporal canthus and vehicle formulation on the other side. Skin roughness, skin hydration, and skin elasticity were evaluated by Primospico, Corneometer® CM825, and Cutometer® MPA580, respectively. The formulation containing 2% ZBM extract has a significant short‐term anti‐crow's feet effect compared with vehicle. No adverse effect was shown during the study. Topical application of 2% ZBM extract is tolerable and can be used as an effective cosmetic agent for short‐term wrinkle treatment.     

Mechanics of wrinkle formation: micromechanical analysis of skin deformation during wrinkle formation in ultraviolet‐irradiated mice

Background/purpose: The mechanical aspects of wrinkle formation were studied in the dorsal skin of hairless mice. Methods: Wrinkles were induced by irradiating with ultraviolet (UV) B for 10 weeks, while observing skin deformation during wrinkle formation. Changes in skin dimensions were also observed during the specimen excision process. Wrinkle depth and interval were measured before and after removal of the cutaneous muscle layer. Local deformation of wrinkled skin during uniaxial stretch was also measured. Changes in curvature of skin specimens upon muscle layer removal were then observed to determine the force balance in skin layers. Results: The skin showed spontaneous contraction in response to UV irradiation. Wrinkled skin showed a marked decrease in the wrinkle depth and a slight increase in wrinkle interval following muscle layer removal, a peculiar mechanical response that cannot be explained by homogeneous deformation of the skin. This response was due to compressive deformations of dermal tissue caused by the muscle layer and concentrated at valleys of the wrinkles. Curvature measurements indicated that the muscle layer compressed the dermal tissue predominantly in the craniocaudal direction. Morphological observations showed that the wrinkles coincided with rows of pores and sulci cutis, where the structural stiffness of the horny layer was relatively low. The horny layer showed significant thickening. Conclusion: Taken together, we propose the following hypothetical mechanisms of wrinkle formation during UV irradiation: spontaneous contraction of the dermis while maintaining or increasing the epidermal area induces buckling of the epidermis into the dermis at mechanically weak lines, namely, the rows of pores and sulci cutis, and buckling may be amplified by the axial compression of the dermis by the muscle layer.     

Hyaluronic acid microneedle patch for the improvement of crow's feet wrinkles

Hyaluronic acid (HA) has an immediate volumizing effect, due to its strong water‐binding potential, and stimulates fibroblasts, causing collagen synthesis, with short‐ and long‐term effects on wrinkle improvement. We investigated the efficacy and safety of HA microneedle patches for crow's feet wrinkles. Using a randomized spilt‐face design, we compared microneedle patches with a topical application containing the same active ingredients. We enrolled 34 Korean female subjects with mild to moderate crow's feet wrinkles. The wrinkle on each side of the subject's face was randomly assigned to a HA microneedle patch or HA essence application twice a week for 8 weeks. Efficacy was evaluated at weeks 2, 4, and 8. Skin wrinkles were measured as average roughness using replica and PRIMOS. Skin elasticity was assessed using a cutometer. Two independent blinded dermatologists evaluated the changes after treatment using the global visual wrinkle assessment score. Subjects assessed wrinkles using the subject global assessment score. Skin wrinkles were significantly reduced and skin elasticity significantly increased in both groups, although improvement was greater in the patch group at week 8 after treatment. In the primary and cumulative skin irritation tests, the HA microneedle patch did not induce any skin irritation. The HA microneedle patch is more effective than the HA essence for wrinkle improvement and is a safe and convenient without skin irritation.     

Evaluation of anti‐wrinkle effects of a novel cosmetic containing niacinamide

Niacinamide is known to have effectiveness on sallowness, wrinkling, red blotchiness and hyperpigmented spots in aging skin. In this study, we have evaluated the anti‐wrinkle effects of a new cosmetic containing niacinamide. A randomized, placebo‐controlled, split face study was performed in 30 healthy Japanese females who had wrinkles in the eye areas. The tested cosmetic containing 4% niacinamide was applied on wrinkles of one side for 8 weeks, and a control cosmetic without niacinamide on another site. Anti‐wrinkle effects were evaluated with two methods: (i) doctors’ observation and photographs based on the guideline of the Japan Cosmetic Industry Association; and (ii) average roughness of skin surface (Ra value) using skin replica. This cosmetic showed marked and moderate improvement in 64% of the subjects with a significant difference as compared with the control site (P < 0.001). Wrinkle grades in the tested area significantly reduced more than pre‐application (P < 0.001) and the control (P < 0.001). Reduction in Ra value on the tested area was more than pre‐application (P < 0.01) and the control site (P < 0.05) with significant differences Only one subject stopped the study with minimal irritation. These results indicated that the tested lotion was well tolerated and may be an optional preparation for the treatment of wrinkles in the eye areas.     

In vitro,ex vivo,and clinical evaluation of anti-aging gel containing EPA and CBD

Background

Skin aging manifestation, such as coarse wrinkles, loss of elasticity, pigmentation, and rough-textured appearance, is a multifactorial process that can be exacerbated by air pollution, smoking, poor nutrition, and sun exposure. Exposure to UV radiation is considered the primary cause of extrinsic skin aging and accounts for about 80% of facial aging. Extrinsic skin aging signs can be reduced with demo-cosmetic formulations. Both cannabidiol (CBD) and eicosapentaenoic acid (EPA) have been previously suggested as potent active dermatological ingredients.

Aims

The objective of the current research was to evaluate the compatibility of both agents in the prevention and treatment of skin aging. First, the impact of both agents was assessed using standard photoaging models of UV-induced damage, both in vitro (HaCaT cells) and ex vivo (human skin organ culture). Then, a clinical validation study (n = 33) was performed using an optimized topical cream formulation tested at different time points (up to Day 56).

Results

EPA was found to potentiate the protective effects of CBD by reducing the secretion of prostaglandin E2 (PGE₂) and interleukin-8 (IL-8), two primary inflammatory agents associated with photoaging. In addition, a qualitative histological examination signaled that applying the cream may result in an increase in extracellular matrix (ECM) remodeling following UV radiation. This was also evidenced clinically by a reduction of crow's feet wrinkle area and volume, as well as a reduction of fine line wrinkle volume as measured by the AEVA system. The well-established age-dependent subepidermal low-echogenic band (SLEB) was also reduced by 8.8%. Additional clinical results showed significantly reduced red spots area and count, and an increase in skin hydration and elasticity by 31.2% and 25.6% following 56 days of cream application, respectively. These impressive clinical results correlated with high satisfaction ratings by the study participants.

Discussion and Conclusions

Collectively, the results show a profound anti-aging impact of the developed formulation and strengthen the beneficial derm-cosmetic properties of CBD-based products.     

Nicotinamide for skin cancer chemoprevention

Nicotinamide (vitamin B₃) has a range of photoprotective effects in vitro and in vivo; it enhances DNA repair, reduces UV radiation‐induced suppression of skin immune responses, modulates inflammatory cytokine production and skin barrier function and restores cellular energy levels after UV exposure. Pharmacological doses of nicotinamide have been shown to reduce actinic keratoses and nonmelanoma skin cancer incidence in high‐risk individuals, making this a nontoxic and accessible option for skin cancer chemoprevention in this population.     

The severity of wrinkling at the forehead is related to the degree of ptosis of the upper eyelid

Background: Most studies on wrinkle formation have focused on changes in the dermal condition that promote the fixation of transiently formed wrinkles. Little is known about the age‐dependent changes in transient wrinkle formation in response to altered facial expression or the mechanism leading to fixed wrinkle formation. Objective: To clarify the mechanism of wrinkle formation at the forehead, we investigated the factors that influence the severity of transient wrinkling and the relationship of transient with fixed wrinkles, using a newly established method to evaluate transient wrinkle formation. Methods: Transient wrinkles were generated by requesting subjects to gaze in an upward direction. Foreheads of the subjects with or without an upward gaze at a fixed angle were photographed and the severity of wrinkles at the forehead was graded from 0 to 5 in 50 healthy Japanese female volunteers in their 20s, 40s, or 60s. Skin elasticity was measured using a Cutometer^®. Frontalis muscle activity and ptosis of the upper eyelid were estimated by measuring movement of the eyebrow during upward gazing and the position of the upper eyelid of the open eye, respectively. Results: Wrinkles formed transiently at the forehead by upward gazing were highly reproducible in each subject. Their severity increased with aging and was highly correlated to that of fixed wrinkles (R=0.81, P<0.001). Therefore, this method appears to be suitable for studying the mechanism of transient wrinkle formation and the relationship between transient and fixed wrinkles at the forehead. The severity of transient wrinkles was correlated with elevation of the eyebrow during upward gazing (R=0.69, P<0.001), but not with dermal elasticity. This suggests that transient wrinkles are induced by increased frontalis muscle activity during upward gazing. Frontalis muscle activation was negatively correlated with upper eyelid position (R=−0.37, P<0.05), which descended with aging, meaning ptosis of the upper eyelid, and negatively correlated with the severity of transient wrinkles induced by upward gazing (R=−0.43, P<0.05). Furthermore, the upper eyelid position was also negatively correlated with the severity of fixed wrinkles (R=−0.44, P<0.05). Conclusion: These results suggest that ptosis of the upper eyelid is associated with increased activation of the frontalis muscle during upward gazing and increased severity of transient and fixed wrinkling at the forehead.     

Novel anti‐wrinkle effect of cosmeceutical product with new retinyl retinoate microsphere using biodegradable polymer

Background: The novel hybrid retinoid, retinyl retinoate, is a synthetic material that was designed to reduce the side effects of retinoic acid and to increase the stability of retinol. The formulation of the retinyl retinoate, however, is required to enhance skin permeation, and thus to increase the anti‐wrinkle effect. Aim: To identify the efficacy of retinyl retinoate microsphere using biodegradable polymer as an anti‐aging agent of cosmetics in treating females over 30 years old with periorbital wrinkles. Methods: The retinyl retinoate microsphere was prepared using the biodegradable polymer; polylactic acid (PLA). We also conducted two clinical studies with a total of 44 Korean women for 12 weeks. In the first clinical study, 20 patients completed a 12‐week trial of cream A [3% PLA‐retinyl retinoate (2%) microsphere] applied twice daily to the face. In the second clinical study, 24 patients completed a 12‐week trial of cream B (0.06% retinyl retinoate) applied twice daily to the face. Efficacy was based on a global photodamage score, photographs, and image analysis using replicas and Visiometers every 4 weeks. Results: The PLA‐retinyl retinoate microsphere was more effective for the permeation of retinyl retinoate than retinyl retinoate in itself. The cream A, which contains 3% PLA‐retinyl retinoate (2%) microsphere, showed a statistically significant improvement in facial wrinkles (P<0.05) in 20 volunteers after only 4 weeks of application in a clinical trial test. The visual wrinkle improvement and the maximum roughness improvement rate (R2) for cream A was 6.05%, 8.03% higher than that of cream B which contains 0.06% retinyl retinoate, after 4 weeks. Conclusion: Retinyl retinoate has a potent anti‐wrinkle activity, and the PLA‐retinyl retinoate microsphere could be a useful cosmeceutical product for anti‐aging purposes.