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To demonstrate the synergistic effect of 4-hexylresorcinol (4-HR) with niacinamide in boosting anti-melanogenic efficacy in vitro and establish the in vivo efficacy and safety of the combination in a human trial.Primary human epidermal melanocytes and 3D pigmented skin equivalents were treated with 4-HR, niacinamide, and their combinations for their effect on pigmentation. This was followed by a randomized, double-blind, split-face clinical study in Chinese subjects, and effects on skin tone, hyperpigmentation, fine lines and wrinkles, hydration, and skin firmness were measured for a 12-week study period.In vitro tyrosinase enzyme activity studies showed that 4-HR is one of the most potent tyrosinase inhibitors. The combination of 4-HR and niacinamide showed a synergistic reduction in melanin production in cultured melanocytes and lightened the 3D skin equivalent model. In vitro as well as in the human trial, the combination of 4-HR and niacinamide showed significantly improved efficacy over niacinamide alone on hyperpigmentation spots as measured by L*, the visual appearance of fine lines and wrinkles in crow's feet and perioral area and skin firmness, with no product-related adverse events.A formulation containing a combination of 4-HR and niacinamide delivered superior skin tone and anti-ageing benefits significantly better than niacinamide alone with no adverse events. This study demonstrates that a product designed to affect multiple pathways of melanogenesis, inflammation, and ageing may provide an additional treatment option, beyond hydroquinone and retinoids, for hyperpigmentation and ageing.Démontrer l’effet synergique du 4-hexylrésorcinol (4-HR) associé au niacinamide pour stimuler in vitro l’efficacité antimélanogène, et établir l’efficacité et la sécurité d’emploi in vivo de cette association dans un essai chez l’homme. MÉTHODES: Des mélanocytes épidermiques humains primaires et des équivalents cutanés pigmentés en 3D ont été traités avec du 4-HR, du niacinamide et leurs combinaisons pour leur effet sur la pigmentation. Ceci a été suivi d’une étude clinique randomisée, en double aveugle en hémi-visage chez des sujets chinois, et les effets sur le teint, l’hyperpigmentation, les rides et ridules, l’hydratation et la fermeté de la peau ont été mesurés pendant une durée d’étude de 12 semaines. RÉSULTATS: Les études in vitro sur l’activité enzymatique de la tyrosinase ont montré que le 4-HR est l’un des inhibiteurs de la tyrosinase les plus puissants. L’association du 4-HR et du niacinamide a montré une réduction synergique de la production de mélanine dans les mélanocytes de culture et donné de la luminosité au modèle cutané 3D équivalent. Également in vitro avec l’étude chez l’homme, l’association du 4-HR et du niacinamide a fait ressortir une efficacité significativement plus élevée qu’avec le niacinamide seul sur les taches d’hyperpigmentation mesurées par L*, l’aspect visuel des rides et ridules des pattes d’oie et de la zone périorale, et la fermeté de la peau, sans événements indésirables liés au produit.Une formulation contenant une association de 4-HR et de niacinamide a permis d’obtenir un teint et un effet anti-âge nettement supérieurs à ceux du niacinamide seul, sans événements indésirables. Cette étude démontre qu’un produit conçu pour toucher plusieurs voies de mélanogenèse, d’inflammation et de vieillissement peut constituer une nouvelle option thérapeutique, au-delà de l’hydroquinone et des rétinoïdes, pour l’hyperpigmentation et le vieillissement.

Objectives: We evaluated the role of 12-hydroxystearic acid (12HSA) in upregulating skin antimicrobial peptides (AMPs) in in vitro and ex vivo assays, and 12HSA provides long-lasting germ protection in vivo through a handwash formulation. Methods: In vitro assays were performed by treating skin cells, maintained in cell-culture media, with 12HSA. After treatment, AMP gene-expression was measured in cells by RT-qPCR, and secreted AMPs in spent cell culture media were analyzed by ELISA. Skin explants were treated with 12HSA, and 3D-living skin equivalent (LSE) models were treated with 12HSA-containing handwash formulations. AMP levels were measured by immunohistochemical staining or RT-qPCR after treatment. In clinical studies, volunteer forearms were washed multiple times with 12HSA-containing handwash in an ethics-approved study in which participants provided informed consent. The washed forearms were challenged with E. coli at different time points after washing. The 12HSA deposition from the formulation was measured using tape strips. Results: Skin cells treated with 12HSA showed increased expression of several AMP genes in vitro, and higher psoriasin AMP secretion was measured in cell-culture media. An enhanced level of LL37 AMP was obtained from the skin epidermis of 12HSA-treated explant skin. AMP genes were also upregulated in the 3D-LSE model treated with a 12HSA-containing handwash formulation. A measurable level of 12HSA was deposited from handwash formulation in the in vivo clinical sample. E. coli recovery from challenged skin was significantly lower at 6 and 10 hours after washing compared to unwashed skin. Conclusions: These data demonstrate that 12HSA boosts skin-AMPs and that a handwash containing 12HSA provides long-lasting germ protection under in vivo test conditions by potentially enhancing skin’s natural immunity. With an emerging understanding of skin’s innate immunity and AMPs, designing cleansing products that strengthen these natural defenses will offer novel approaches to extend hygiene benefits beyond immediate in-wash protection.

Facial skin characteristics and appearance vary according to ethnicity. While much of this knowledge is derived from the Caucasian population, lately there have been efforts to gain such understanding in various regions in Asia. In this paper, we have built an understanding of such features in Indonesia. In Indonesia, a section of females wears a traditional veil (hijab) to cover the scalp and part of face. The influence of the hijab on facial skin attributes was also investigated.In a cross-sectional observational study design involving 419 female volunteers in Jakarta, Indonesia, facial skin attributes (colour, radiance, hydration, trans-epidermal water loss [TEWL], wrinkles, fine lines, pores, and sebum levels) and conditions (melasma, post-inflammatory hyperpigmentation (PIH), solar lentigines/ senile lentigines, seborrheic keratoses and acne) were assessed by trained operators and dermatologists using standard validated instruments and scales.With age, facial skin colour showed darkening in cheek; forehead on the other hand showed slight lightening. The skin evenness and radiance decreased, substantially. Aging attributes measured in terms of lines, wrinkles, and under-eye dark circles showed deterioration with age; the decline was progressively faster than colour change. Facial image data analysis corroborated these findings. Skin hydration remained similar across the age groups even though the skin barrier function measured in terms of TEWL improved with age. Sebum levels in the skin were similar up to the age of 50 but declined in the next group of 50-60 year. Pore severity increased with age. Melasma, seborrheic keratosis and PIH showed a high prevalence (∼50%) at the young age group (20-30 years), itself. Melasma prevalence attained 100% in the age group of 41-50 year and onwards, and its severity similarly showed a steady rise with age. PIH on the other hand showed a steady decline with age. Solar lentigines prevalence (∼30%) did not change much across age groups, and the severity scores were similar in age groups up to 50 year but increased substantially in 51-60-year age groups. Seborrheic keratosis was similar (∼47%) in age groups up 20-40 year but steadily increased in upper age groups. Its severity was similar in the age groups of 20-30 year and 31-40 year but showed a two-fold increase in subsequent age groups. Acne was 10% in the age group of 20-30 year and declined gradually to 0.7% in the 51-60-year age group. Hijab wearers showed slight protection in skin colour darkening and improvement of evenness and radiance but were similar on aging (fine lines and wrinkles on crow's feet, under eye and peri-oral areas) markers to non-wearers. In general, in majority of age-groups, hijab wearers showed a higher prevalence of melasma, solar/senile lentigines, seborrheic keratosis and PIH.