Vitiligo is an autoimmune disease with a localized or generalized depigmentation in the skin, and characterized by psychological stress induced by unattractive appearance. Psychological stress induces alterations in immune cell populations through hormones and cytokines, however, the pathogenesis of psychological stress on vitiligo remains unclear. This review discussed the effects of psychological stress-derived hormones and cytokines including macrophage migration inhibitory factor, progesterone, glucocorticoids, estrogens, and norepinephrine on immunocytes including regulatory T cells, natural killer cells, dendritic cells, B cells, monocytes, and neutrophils. In addition, the review also explored the relationship between melanocytes and immune cells, as well as the conditions of several major animal models simulating the peripheral blood in human vitiligo. This review intended to provide better insights into the complex pathogenesis of vitiligo related to psychological stress, and developing new targets for the prevention and treatments of vitiligo.

Purpose: Vitiligo is an autoimmune disease that results in the loss of epidermal melanocytes. The treatments for patients with vitiligo remain lacking. Erzhiwan (EZW), a traditional Chinese Medicine composed of Ligustri Lucidi Fructus and Ecliptae Herba, was used to ameliorate depigmentation since ancient China. This study aims to investigate the effect of EZW on vitiligo-related depigmentation. Methods: A vitiligo-related depigmentation mouse model was induced by monobenzone and restraint stress. The experimental depigmentation mice were treated with EZW. Histological observation of skin was conducted. Cutaneous oxidative damage and inflammation were determined. A network pharmacology analysis was carried out. Results: EZW reduced depigmentation score (p< 0.01), cutaneous inflammatory infiltration (p< 0.01), and CD8α-positive expression (p< 0.01), and increased cutaneous melanin content in experimental depigmentation mice. EZW reduced stress reaction in experimental depigmentation mice (p< 0.01). EZW inhibited 8-hydroxy-2-deoxyguanosine (8-OHdG)-related DNA oxidative damage in the skin (p< 0.05, p< 0.01). In addition, EZW reduced cutaneous macrophage migration inhibitory factor (MIF)-CD74-NF-κB signaling (p< 0.01). The network pharmacology analysis demonstrated that EZW regulated necroptosis, apoptosis, and FoxO signaling pathways in vitiligo. An in vitro experiment showed that the main ingredient of EZW, specnuezhenide, protected against monobenzone and MIF-induced cell death in HaCaT cells (p< 0.01). Conclusion: EZW ameliorates restraint stress- and monobenzone-induced depigmentation via the inhibition of MIF and 8-OHdG signaling. The findings provide a data basis of an utilization of EZW in vitiligo.