Superior even skin tone and anti-ageing benefit of a combination of 4-hexylresorcinol and niacinamide.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

OBJECTIFS: 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. CONCLUSIONS: 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.

Compositional variation among black tea across geographies and their potential influence on endothelial nitric oxide and antioxidant activity.

Black tea (C. sinensis) consumption is well associated with enhanced endothelial function (EF) and reduced cardiovascular (CV) risk. This clinical end benefit is endorsed to flavonoids in tea. The black tea flavonoid composition varies across geographies and may impact its health benefits. Moreover, the underlying functional species and a precise working mechanism responsible for the observed health benefit also remain to be investigated. In this Article, we investigated the effect of black teas from various geographies (WoBTs) on different working mechanisms (antioxidant potential and endothelial function) proposed to influence certain risk factors of CVH, in vitro. Pearson correlation analysis showed that the antioxidant benefits are fairly influenced by majority of tea actives such as catechins, theaflavins, thearubigins, and phenolic acids, while NO potentiating effects are mainly regulated by catechins in black tea. The data also suggest that the net vascular function benefit of black tea is majorly influenced by NO enhancement, while mildly contributed by its antioxidant benefit.

Nonclassical MHC-I and Japanese encephalitis virus infection: induction of H-2Q4, H-2T23 and H-2T10.

Nonclassical MHC Class 1b antigens differ from classical MHC class 1a antigens in having a restricted polymorphism as well as varied surface expression in different cell types. They have been hypothesized to play a role in bridging adaptive and innate immune responses. We examined the effects of JEV infection on the expression of classical MHC class 1a and nonclassical MHC class 1b genes in five different cell lines. Among the nonclassical genes, H-2Q4 was induced in H-6 hepatoma, primary astrocytes, mouse embryo fibroblasts, L929 and 3T3 cells. H-2T23 and H-2T10 genes were not induced in H-6 and 3T3, respectively, but were induced in the other cell lines examined. Both H-2Q4 encoded Qb1 and H-2T23 encoded Qa-1(b) antigens were induced on the cell surface upon JEV infection in primary astrocytes and mouse embryonic fibroblasts. Classical MHC-I genes and the genes associated with antigen presentation such as Tap1, Tap2, Tapasin, Lmp2, Lmp7 and Lmp10 as well as type 1 (alpha/beta) IFNs were induced in all cell lines. However, IFNgamma was not induced. Further, induction of H-2Q4 and H-2T23 by JEV was independent of NF-kappaB but type 1 IFN dependent while H-2T10 was dependent on NF-kappaB and type 1 IFN independent. Thus, while classical MHC genes were induced by JEV in all cell lines tested despite high levels of constitutive expression in L929 and 3T3, nonclassical genes were not inducible in all cell lines tested and involved different mechanisms of induction.

Cutting edge: the silent chemokine receptor D6 is required for generating T cell responses that mediate experimental autoimmune encephalomyelitis.

D6, a promiscuous nonsignaling chemokine binding molecule expressed on the lymphatic endothelium, internalizes and degrades CC chemokines, and D6(-/-) mice demonstrated increased cutaneous inflammation following topical phorbol ester or CFA injection. We report that D6(-/-) mice were unexpectedly resistant to the induction of experimental autoimmune encephalomyelitis due to impaired encephalitogenic responses. Following induction with myelin oligodendroglial glycoprotein (MOG) peptide 35-55 in CFA, D6(-/-) mice showed reduced spinal cord inflammation and demyelination with lower incidence and severity of experimental autoimmune encephalomyelitis attacks as compared with D6(+/+) littermates. In adoptive transfer studies, MOG-primed D6(+/-) T cells equally mediated disease in D6(+/+) or D6(-/-) mice, whereas cells from D6(-/-) mice transferred disease poorly to D6(+/-) recipients. Lymph node cells from MOG-primed D6(-/-) mice showed weak proliferative responses and made reduced IFN-gamma but normal IL-5. CD11c(+) dendritic cells accumulated abnormally in cutaneous immunization sites of D6(-/-) mice. Surprisingly, D6, a "silent" chemokine receptor, supports immune response generation.