Protective effects of Thai silk sericins and their related mechanisms on UVA-induced phototoxicity and melanogenesis: Investigation in primary melanocyte cells using a proteomic approach.

UV radiation causes excess production of melanin as a result of hyperpigmentation and skin disorders. Silk sericin exhibited bioactivities to skin and inhibited UV-induced phototoxicity and melanogenesis in skin cells; however, the mechanism related to sericin against UV-induced melanogenesis has not been investigated. This study aimed to investigate the protective effects of Thai silk sericins against UVA-induced phototoxicity and melanogenesis and their related mechanisms. Thai silk sericins exhibited cytoprotective effects against UV-induced toxicity in human primary melanocytes by attenuation of cytotoxicity, intracellular ROS generation, and mitochondrial potential impairment. Pre- and post-treatment with sericin significantly inhibited melanin synthesis and tyrosinase activity against UVA exposure. In addition, sericin S2 could reduce the basal melanin content in zebrafish embryos. The proteomic analysis demonstrated that Thai silk sericins altered the protein expression in melanocytes especially proteins related to stress, inflammatory, cytokine stimulation, cell proliferation, and cell survival processes that contribute to cytoprotective effect and inhibitory effect on melanogenesis of sericin. Moreover, we demonstrated the novel mechanism of Thai silk sericins in inhibiting UVA-induced melanogenesis via increasing BMP4 expression in MAPK/ERK signaling pathway. These evidences support the potential use of Thai silk sericins in prevention of hyperpigmentation in skin disorders especially after UVA exposure.

Protective effect of Thai silk extracts on drug-induced phototoxicity in human epidermal A431 cells and a reconstructed human epidermis model.

Bombyx mori silk extracts, derived from the cocoon degumming process of draw and dye silk in the textile industry, are mainly composed of sericin protein. To add value to the Thai silk extracts, and hence the silk industry, a simple enrichment process was recently developed and the enriched silk extracts were then applied in nano-cosmeceutical products and nano-delivery systems. In this study, the protective effect of Thai silk extracts from three different strains of Bombyx mori on the drug-induced phototoxicity was evaluated in vitro using chlorpromazine (CPZ), a commonly used antipsychotic drug, as a representative phototoxic drug. The human epidermal A431 cell line and reconstructed human epidermis (RhE) model were used as the in vitro skin model. The silk extracts significantly improved the viability of A431 cells after CPZ exposure and ultraviolet A (UVA) irradiation, as shown by the significantly increased CPZ and UVA IC50 values and the decreased proportion of apoptotic cells. The protective effect of these silk extracts against the CPZ-induced UVA-phototoxicity in A431 cells was associated with the attenuation of intracellular oxidative stress via an increased intracellular glutathione level. Likewise, the silk extracts exhibited a protective effect on the CPZ-induced UVA-phototoxicity in the RhE model, in terms of an improved tissue viability and attenuation of the released inflammatory cytokine, interleukin-1α. These findings support the potential usefulness of silk extracts in novel applications, especially in the protection of drug-induced phototoxicity.

Human primary erythroid cells as a more sensitive alternative in vitro hematological model for nanotoxicity studies: Toxicological effects of silver nanoparticles.

Although immortalized cells established from cancerous cells have been widely used for studies in nanotoxicology studies, the reliability of the results derived from immortalized cells has been questioned because of their different characteristics from normal cells. In the present study, human primary erythroid cells in liquid culture were used as an in vitro hematological cell model for investigation of the nanotoxicity of silver nanoparticles (AgNPs) and comparing the results to the immortalized hematological cell lines HL60 and K562. The AgNPs caused significant cytotoxic effects in the primary erythroid cells, as shown by the decreased cell viability and induction of intracellular ROS generation and apoptosis, whereas they showed much lower cytotoxic and apoptotic effects in HL60 and K562 cells and did not induced ROS generation in these cell lines. Scanning electron microcopy revealed an interaction of AgNPs to the cell membrane in both primary erythroid and immortalized cells. In addition, AgNPs induced hemolysis in the primary erythroid cells in a dose-dependent manner, and transmission electron microcopy analysis revealed that AgNPs damaged the erythroid cell membrane. Taken together, these results suggest that human primary erythroid cells in liquid culture are a more sensitive alternative in vitro hematological model for nanotoxicology studies.