Abstract

Background Kursi Karwiya or caraway tablet (CWT), a traditional medicine formula, is widely used in Xinjiang, China, for treating vitiligo, a common autoimmune disease for which there is currently no satisfactory cure. Clinical interventions include pharmacological treatment with psoralens, often in conjunction with UVA radiation, but toxic side effects limit this application. Studies on the activities and mechanisms of CWT are scarce. Objective To investigate the in vitro and in vivo effects of CWT in B16 cell line and in animal models of vitiligo, further exploring its mechanisms of regulating melanogenesis. Methods Effects of CWT on melanin synthesis in B16 cells and mushroom tyrosinase activity were investigated in vitro. The signaling pathway of melanogenesis in murine B16 melanoma cells was examined by Western blotting. Two different animal models were used, vitiligo induced by hydroquinone in the mouse model and by hydrogen peroxide in the guinea pig model. Relevant biochemical parameters in blood and skin tissue were measured, and visual inspection, histopathology, and immunohistochemical analysis of treated areas were carried out. Results CWT produced changes in biochemical parameters including TYR, MDA, MAO, AChE, IL-6, INF-α, β-EP, and cAMP in blood and/or skin tissue and in regulating melanogenesis. After treatment with CTW, skin color, melanin containing hair follicles, and expression of TYR, TRP-1, and TRP-2 in the skin of animals were significantly affected. Conclusions CWT alleviated many of detrimental effects in both models of vitiligo. Tyrosinase activity and melanin content in B16 cells were increased, at least in part, via activation of the PKA p38 MAPK signaling pathways. Our results show that CWT produces beneficial effects on parameters of vitiligo and is worthy of further investigation for use in this distressing autoimmune disorder which currently has no effective cure.

Highlights

  • Vitiligo is an autoimmune cutaneous disease of pigmentation, characterized by the development of well-defined white patches on the skin and mucous membranes [1]

  • Despite its long history of use, the pharmacological mechanisms behind the effects of caraway tablet (CWT) have not been elucidated. We have investigated these in validated mouse and guinea pig models of vitiligo, induced by hydroquinone and hydrogen peroxide, respectively, and its mechanisms in regulating melanogenesis and involvement of PKA signaling

  • Psoralea corylifolia, Tribulus terrestris, and Trachyspermum ammi seeds and Operculina turpethum root were identified, and voucher specimens were kept at the Xinjiang Technical Institute of Physics and Chemistry, Urumqi. e preparation of extract of CWT was based on previous methods (Patent No CN 107569532 A). e protocol for preparation of caraway tablet is given in Supplementary Materials

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Summary

Introduction

Vitiligo is an autoimmune cutaneous disease of pigmentation, characterized by the development of well-defined white patches on the skin and mucous membranes [1]. Clinical interventions include pharmacological treatment with psoralens, often in conjunction with UVA radiation, but toxic side effects limit this application. To investigate the in vitro and in vivo effects of CWT in B16 cell line and in animal models of vitiligo, further exploring its mechanisms of regulating melanogenesis. Effects of CWT on melanin synthesis in B16 cells and mushroom tyrosinase activity were investigated in vitro. CWT produced changes in biochemical parameters including TYR, MDA, MAO, AChE, IL-6, INF-α, β-EP, and cAMP in blood and/or skin tissue and in regulating melanogenesis. Our results show that CWTproduces beneficial effects on parameters of vitiligo and is worthy of further investigation for use in this distressing autoimmune disorder which currently has no effective cure

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