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Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway.
Free Radic Biol Med. 2018 12; 129:492-503.FR

Abstract

Vitiligo is a complex disorder characterized by patchy loss of skin pigmentation due to abnormal melanocyte function. Overwhelming evidences have suggested that oxidative stress plays a major role in the loss of melanocytes thereby mediating the onset and progression of vitiligo. The nuclear factor erythroid 2-like factor 2 (Nrf2) is a master regulator of cellular redox homeostasis and the activation of Nrf2 signaling pathway is impaired in the vitiligo melanocytes. Baicalein, as flavonoid extracted from the Scutellaria baicalensis, has been proved to possess the ability to activate Nrf2 signaling pathway in other cell types and mouse model. Our previous data found that baicalein exerts a cytoprotective role in H2O2-induced apoptosis in human melanocytes cell line (PIG1). Based on these founding, we hypothesized that baicalein activates Nrf2 signaling pathway, alleviates H2O2-induced mitochondrial dysfunction and cellular damage, thereby protecting human vitiligo melanocytes from oxidative stress. In the present study, we found that baicalein effectively inhibited H2O2-induced cytotoxicity and apoptosis in human vitiligo melanocytes (PIG3V). Further results demonstrated that baicalein promoted Nrf2 nucleus translocation as well as up-regulated the expression of Nrf2 and its target gene, heme oxygenase-1 (HO-1). Moreover, the protective effects of baicalein against H2O2-induced cellular damage and apoptosis as well as mitochondrial dysfunction were abolished by Nrf2 knockdown. Additionally, we observed that Nrf2 knockdown suppressed proliferation and increased the sensitivity of PIG3V cells to H2O2 treatment. Finally, we explored the mechanism of baicalein associated with Nrf2 activation and found that the phosphorylation of Nrf2 as well as ERK1/2and PI3K/AKT signaling were not involved in the baicalein-induced activation of Nrf2. Taken together, these data clearly suggest that baicalein enhances cellular antioxidant defense capacity of human vitiligo melanocytes through the activation of the Nrf2 signaling pathway, providing beneficial evidence for the application of baicalein in the vitiligo treatment.

Authors+Show Affiliations

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. Electronic address: lbm009@163.com.Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. Electronic address: lichying@fmmu.edu.cn.Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. Electronic address: xjzhejian@fmmu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30342186

Citation

Ma, Jingjing, et al. "Baicalein Protects Human Vitiligo Melanocytes From Oxidative Stress Through Activation of NF-E2-related Factor2 (Nrf2) Signaling Pathway." Free Radical Biology & Medicine, vol. 129, 2018, pp. 492-503.
Ma J, Li S, Zhu L, et al. Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway. Free Radic Biol Med. 2018;129:492-503.
Ma, J., Li, S., Zhu, L., Guo, S., Yi, X., Cui, T., He, Y., Chang, Y., Liu, B., Li, C., & Jian, Z. (2018). Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway. Free Radical Biology & Medicine, 129, 492-503. https://doi.org/10.1016/j.freeradbiomed.2018.10.421
Ma J, et al. Baicalein Protects Human Vitiligo Melanocytes From Oxidative Stress Through Activation of NF-E2-related Factor2 (Nrf2) Signaling Pathway. Free Radic Biol Med. 2018;129:492-503. PubMed PMID: 30342186.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway. AU - Ma,Jingjing, AU - Li,Shuli, AU - Zhu,Longfei, AU - Guo,Sen, AU - Yi,Xiuli, AU - Cui,Tingting, AU - He,Yuanmin, AU - Chang,Yuqian, AU - Liu,Bangmin, AU - Li,Chunying, AU - Jian,Zhe, Y1 - 2018/10/18/ PY - 2018/05/30/received PY - 2018/08/26/revised PY - 2018/10/09/accepted PY - 2018/10/21/pubmed PY - 2019/9/29/medline PY - 2018/10/21/entrez KW - Baicalein KW - Melanocytes KW - Mitochondria KW - Nrf2 KW - Vitiligo SP - 492 EP - 503 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 129 N2 - Vitiligo is a complex disorder characterized by patchy loss of skin pigmentation due to abnormal melanocyte function. Overwhelming evidences have suggested that oxidative stress plays a major role in the loss of melanocytes thereby mediating the onset and progression of vitiligo. The nuclear factor erythroid 2-like factor 2 (Nrf2) is a master regulator of cellular redox homeostasis and the activation of Nrf2 signaling pathway is impaired in the vitiligo melanocytes. Baicalein, as flavonoid extracted from the Scutellaria baicalensis, has been proved to possess the ability to activate Nrf2 signaling pathway in other cell types and mouse model. Our previous data found that baicalein exerts a cytoprotective role in H2O2-induced apoptosis in human melanocytes cell line (PIG1). Based on these founding, we hypothesized that baicalein activates Nrf2 signaling pathway, alleviates H2O2-induced mitochondrial dysfunction and cellular damage, thereby protecting human vitiligo melanocytes from oxidative stress. In the present study, we found that baicalein effectively inhibited H2O2-induced cytotoxicity and apoptosis in human vitiligo melanocytes (PIG3V). Further results demonstrated that baicalein promoted Nrf2 nucleus translocation as well as up-regulated the expression of Nrf2 and its target gene, heme oxygenase-1 (HO-1). Moreover, the protective effects of baicalein against H2O2-induced cellular damage and apoptosis as well as mitochondrial dysfunction were abolished by Nrf2 knockdown. Additionally, we observed that Nrf2 knockdown suppressed proliferation and increased the sensitivity of PIG3V cells to H2O2 treatment. Finally, we explored the mechanism of baicalein associated with Nrf2 activation and found that the phosphorylation of Nrf2 as well as ERK1/2and PI3K/AKT signaling were not involved in the baicalein-induced activation of Nrf2. Taken together, these data clearly suggest that baicalein enhances cellular antioxidant defense capacity of human vitiligo melanocytes through the activation of the Nrf2 signaling pathway, providing beneficial evidence for the application of baicalein in the vitiligo treatment. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/30342186/Baicalein_protects_human_vitiligo_melanocytes_from_oxidative_stress_through_activation_of_NF_E2_related_factor2__Nrf2__signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(18)32194-4 DB - PRIME DP - Unbound Medicine ER -