Clinical, Cosmetic and Investigational Dermatology (Jan 2024)
Erzhiwan Ameliorates Restraint Stress- and Monobenzone-Induced Depigmentation in Mice by Inhibiting Macrophage Migration Inhibitory Factor and 8-Hydroxy-2-Deoxyguanosine
Abstract
Nan Tang,1,* Xiao-Ting Liu,2,* Xiao-Li Lin,2 Wen-Xiu Yang,2 Qi-Lin Li,3 Guo-En Wang,2 Yan-Hua Wu1 1Departments of Traditional Chinese Medicine, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, 510220, People’s Republic of China; 2School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of China; 3Departments of Dermatology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, 510220, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Hua Wu, No. 396 Tongfu Zhong Road, Guangzhou, Guangdong Province, 510220, People’s Republic of China, Email [email protected] Guo-En Wang, No. 280, Waihuan East Road, University Town, Guangzhou, Guangdong Province, 510006, People’s Republic of China, Email [email protected]: 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.Keywords: vitiligo, 8-hydroxy-2-deoxyguanosine, Ligustri Lucidi Fructus, Ecliptae Herba, specnuezhenide
