stilbenes and Vitiligo

Vitiligo is a de-pigmenting skin disorder characterized by white patches on skin due to partial or complete loss of melanocytes. Psoralen in combination with ultraviolet-A (PUVA) acts by stimulation of melanin content and tyrosinase activity in melanocytes. Resveratrol, a sirtuin activator and a potential anti-oxidant reduce oxidative stress which is one of the triggering factors for initiation of vitiligo. Despite their therapeutic activity, weak percutaneous permeability of psoralen and poor solubility of resveratrol hinders their effective topical administration. The aim of present study is to formulate ultradeformable liposomes (UDL) co-loaded with psoralen and resveratrol for evaluation of PUVA and anti-oxidant combination in vitiligo treatment. For this purpose, UDL composed of DC-Chol, cholesterol and sodium deoxy cholate were prepared for their co-delivery. Liposomal carriers were characterized and evaluated for their efficacy using B16F10 cell line. Free radical scavenging potential was also determined for these carriers by in vitro anti-oxidant assays. Optimal co-loaded UDL with particle size ranging from 120 to 130nm, zeta potential of +46.2mV, entrapment efficiency of 74.09% (psoralen) and 76.91% (resveratrol) were obtained. Compared to control, co-loaded UDL showed significant stimulation of melanin and tyrosinase activity with major contribution of psoralen. Further, co-loaded UDL also exhibited potential free radical scavenging activity where resveratrol played a key role. Hence, psoralen and resveratrol co-loaded UDL acts in vitiligo through dual mechanisms of action viz., stimulation of melanin and tyrosinase activity as well as by anti-oxidant activity. These findings indicate that psoralen and resveratrol co-loaded UDL has the promising therapeutic potential for the treatment of vitiligo.

Topics: Animals; Biological Transport; Cell Line, Tumor; Cell Survival; Drug Compounding; Drug Liberation; Ficusin; Kinetics; Liposomes; Melanins; Mice; Monophenol Monooxygenase; Particle Size; Resveratrol; Stilbenes; Vitiligo

Vitiligo is an acquired and progressive hypomelanotic disease that manifests as circumscribed depigmented patches on the skin. The aetiology of vitiligo remains unclear, but recent experimental data underline the interactions between melanocytes and other typical skin cells, particularly keratinocytes. Our previous results indicate that keratinocytes from perilesional skin show the features of damaged cells. Sirtuins (silent mating type information regulation 2 homolog) 1, well-known modulators of lifespan in many species, have a role in gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection and healthy ageing. In the literature there is no evidence for SIRT1 signalling in vitiligo and its possible involvement in disease progression. Here, biopsies were taken from the perilesional skin of 16 patients suffering from non-segmental vitiligo and SIRT1 signalling was investigated in these cells. For the first time, a new SIRT1/Akt, also known as Protein Kinase B (PKB)/mitogen-activated protein kinase (MAPK) signalling has been revealed in vitiligo. SIRT1 regulates MAPK pathway via Akt-apoptosis signal-regulating kinase-1 and down-regulates pro-apoptotic molecules, leading to decreased oxidative stress and apoptotic cell death in perilesional vitiligo keratinocytes. We therefore propose SIRT1 activation as a novel way of protecting perilesional vitiligo keratinocytes from damage.

Topics: Acetylation; Adult; Antioxidants; Apoptosis; Caspase 3; Cell Survival; Dinoprost; Dose-Response Relationship, Drug; Enzyme Activation; Humans; Keratinocytes; MAP Kinase Kinase Kinase 5; MAP Kinase Signaling System; Middle Aged; Mitochondria; Mitogen-Activated Protein Kinases; Oxidative Stress; Phosphorylation; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Resveratrol; RNA, Small Interfering; Sirtuin 1; Skin; Stilbenes; Superoxides; Vitiligo