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Ultraviolet-B (UVB) exposure on the skin triggers apoptosis, oxidative stress and acute inflammatory responses, which eventually increases the risk of various skin disorders. Hemin, an iron-binding porphyrin, has been clinically used for porphyria treatment. However, whether hemin contributes to the skin protection against UVB injury remains to be elucidated. Here, we found that hemin treatment (10 and 20 mg/kg) by intraperitoneal administration could dramatically relieve UVB irradiation-induced skin damage featured by erythema, edema, epidermal hyperplasia and collagen loss in C57BL/6 J mice. Importantly, hemin treatment attenuated UVB irradiation-triggered cell apoptosis in skin epidermis. Consistently, hemin (10, 20 μM) treatment decreased Caspase-3 activation and protected against UVB-induced apoptosis in HaCaT cells. Besides, hemin treatment reduced the infiltration of neutrophils in skin under UVB irradiation, thus restrained neutrophil extracellular traps (NET) formation and myeloperoxidase (MPO) release. We further revealed that hemin inhibited the expression of inflammation associated cytokines and chemokines in UVB-induced HaCaT cells and blocked the chemotaxis of dHL-60 cells to preconditioned media from HaCaT culture upon UVB irradiation. Furthermore, hemin inhibited the excessive maturation and mobilization of bone marrow neutrophils and rectified the proportion of abnormally elevated neutrophils in the blood under UVB irradiation. In conclusion, our study showed that hemin treatment protects against UVB-induced skin damage through inhibiting keratinocytes apoptosis, and suppressing neutrophils infiltration in the skin via externally restraining the keratinocyte attraction and internally regulating bone marrow neutrophil maturation and mobilization, suggesting that hemin is an effective drug candidate for the therapy of UVB damage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Zika virus (ZIKV) is a flavivirus that causes severe neuropathology in newborns and adults. There is no ZIKV-specific treatment or preventative. Therefore, it is urgent to develop safe and effective anti-ZIKV agents. Hemin, an iron-binding porphyrin, has been authorized by FDA to treat acute porphyria since the 1970s. Here, we aim to evaluate the anti-ZIKV effect of hemin in SNB-19 cells (a human glioma cell line) and explore the underlying mechanism based on the virus life cycle and functions of the host cell. Our study found that hemin has a strong activity to protect SNB-19 cells from ZIKV infection presented by decreased expression of viral proteins and virus yield. Meanwhile, ZIKV infection caused STAT1/IRF1 signaling activation and induced inflammatory responses in SNB-19 cells, which was relieved by hemin treatment. HO-1 has been reported to be potently induced by hemin and play a broad-spectrum antiviral effect. Intriguingly, hemin could still exert anti-ZIKV activity upon HO-1 siRNA treatment. Then, we conducted a time-of-addition assay, the result indicated hemin works mainly by interfering with the virus entry process. Further experiments excluded the effects of hemin on AXL-dependent viral adsorption and clathrin-mediated endocytosis processes. Subsequently, by fluorescence spectroscopy studies, intracellular fusion assay and syncytia formation assay, we revealed that hemin acts on the process of virus-endosome fusion. This study elaborated that hemin could play anti-ZIKV activity by disrupting the virus-endosome fusion process and shed new light on developing novel agents against ZIKV infection. [Display omitted] [ABSTRACT FROM AUTHOR]