4-(1-phenylethyl)resorcinol and Hyperpigmentation

Oligonucleotide-based materials such as spherical nucleic acid (SNA) have been reported to exhibit improved penetration through the epidermis and the dermis of the skin upon topical application. Herein, we report a self-assembled, skin-depigmenting SNA structure, which is based upon a bifunctional oligonucleotide amphiphile containing an antisense oligonucleotide and a tyrosinase inhibitor prodrug. The two components work synergistically to increase oligonucleotide cellular uptake, enhance drug solubility, and promote skin penetration. The particles were shown to reduce melanin content in B16F10 melanoma cells and exhibited a potent antimelanogenic effect in an ultraviolet B-induced hyperpigmentation mouse model.

Topics: Animals; Benzhydryl Compounds; Cell Line, Tumor; Down-Regulation; Enzyme Inhibitors; Female; Hyperpigmentation; Melanins; Mice, Inbred C57BL; Monophenol Monooxygenase; Oligonucleotides, Antisense; Prodrugs; Receptor, Melanocortin, Type 1; Resorcinols; Skin; Skin Lightening Preparations; Ultraviolet Rays

Melanin plays a crucial role in protecting human skin against exposure to ultraviolet (UV) radiation. However, its overproduction induces hyperpigmentation disorders of the skin.. To investigate effects of phenylethyl resorcinol as one resorcinol derivative on melanogenesis and its mechanisms using B16F10 mouse melanoma cells and human epidermal melanocytes.. Effects of phenylethyl resorcinol on melanogenesis and its mechanism of action were examined using several in vitro assays (i.e., cell survival, melanin content, cellular tyrosinase activity, real-time PCR analysis, luciferase-reporter assay, Western blot analysis, and ELISAs for cyclic AMP (cAMP), protein kinase A (PKA), cAMP response element binding (CREB) protein, and mitogen-activated protein kinases (MAPKs)).. Phenylethyl resorcinol reduced both melanin content and tyrosinase activity in these cells. Phenylethyl resorcinol also suppressed tyrosinase activity in cell-free tyrosinase enzyme assay. Although phenylethyl resorcinol decreased mRNA levels of tyrosinase and tyrosinase-related protein (TRP)-2, it did not affect mRNA levels of melanogenic gene microphthalmia-associated transcriptional factor (MITF) or TRP-1. Phenylethyl resorcinol had no effects on cAMP signaling or NF-κB signaling based on results of cyclic AMP response element (CRE)-luciferase reporter assay, cAMP production, protein kinase A (PKA) activity, Western blot assays for phosphorylated CRE-binding protein (CREB), NF-κB-luciferase reporter assay, and Western blot assays for phosphorylated NF-κB. However, phenylethyl resorcinol induced activation of activator protein-1 (AP-1) signaling. Specifically, phenylethyl resorcinol increased AP-1 reporter activity and increased phosphorylation of p44/42 MAPK, but not p38 MAPK or c-Jun N-terminal kinase (JNK). MEK1/2 and Src, upstream molecules of p44/42 MAPK were also phosphorylated by phenylethyl resorcinol. In addition, phenylethyl resorcinol-induced decreases in melanin content, tyrosinase activity, and MITF protein levels were attenuated by PD98059, a p44/42 MAPK inhibitor.. These data indicate that the anti-melanogenic activity of phenylethyl resorcinol is mediated by activation of p44/42 MAPK, indicating that phenylethyl resorcinol may be a potential therapeutic agent for treating hyperpigmentation skin disorders.

Topics: Animals; Benzhydryl Compounds; Cells, Cultured; Flavonoids; Gene Expression Regulation; Humans; Hyperpigmentation; MAP Kinase Signaling System; Melanins; Melanocytes; Melanoma; Mice; Microphthalmia-Associated Transcription Factor; Monophenol Monooxygenase; Phosphorylation; Resorcinols

Solar lentigines are common benign macular hyperpigmented lesions localized on sun-exposed areas.. To evaluate the efficacy and safety of a new depigmenting agent containing a retinoid (retinaldehyde), a new phenolic agent (4-(1-phenylethyl)-resorcinol) and a reducing agent (δ-tocopheryl-β-D-glucopyranoside) in the topical treatment of solar lentigines.. Twenty patients with solar lentigines of the face and hands applied the depigmenting agent on each lentigo once daily for 12 weeks. The outcome was evaluated at 45 days (T1) and 3 months (T2) after the end of treatment compared to baseline (T0) by means of clinical evaluation, Mexameter® and Visioface devices for digital and ultraviolet computerized image analysis of skin color as well as in vivo reflectance confocal microscopy.. Image analysis and confocal laser reflectance microscopy showed that hyperpigmentation was significantly reduced at T2 compared to baseline and to controls.. The study treatment was well tolerated and showed significant improvement in the depigmentation of solar lentigines.

Topics: Adult; Drug Combinations; Facial Dermatoses; Female; Glucosides; Hand Dermatoses; Humans; Hyperpigmentation; Image Processing, Computer-Assisted; Lentigo; Microscopy, Confocal; Middle Aged; Reducing Agents; Resorcinols; Retinaldehyde; Skin Lightening Preparations; Tocopherols