PMID- 30342186 OWN - NLM STAT- MEDLINE DCOM- 20190927 LR - 20190927 IS - 1873-4596 (Electronic) IS - 0891-5849 (Linking) VI - 129 DP - 2018 Dec TI - Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway. PG - 492-503 LID - S0891-5849(18)32194-4 [pii] LID - 10.1016/j.freeradbiomed.2018.10.421 [doi] AB - 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 H(2)O(2)-induced apoptosis in human melanocytes cell line (PIG1). Based on these founding, we hypothesized that baicalein activates Nrf2 signaling pathway, alleviates H(2)O(2)-induced mitochondrial dysfunction and cellular damage, thereby protecting human vitiligo melanocytes from oxidative stress. In the present study, we found that baicalein effectively inhibited H(2)O(2)-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 H(2)O(2)-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 H(2)O(2) 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. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Ma, Jingjing AU - Ma J AD - Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. FAU - Li, Shuli AU - Li S AD - Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. FAU - Zhu, Longfei AU - Zhu L AD - Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. FAU - Guo, Sen AU - Guo S AD - Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. FAU - Yi, Xiuli AU - Yi X AD - Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. FAU - Cui, Tingting AU - Cui T AD - Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. FAU - He, Yuanmin AU - He Y AD - Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. FAU - Chang, Yuqian AU - Chang Y AD - Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. FAU - Liu, Bangmin AU - Liu B AD - Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. Electronic address: lbm009@163.com. FAU - Li, Chunying AU - Li C AD - Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. Electronic address: lichying@fmmu.edu.cn. FAU - Jian, Zhe AU - Jian Z AD - Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. Electronic address: xjzhejian@fmmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181018 PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 RN - 0 (Antioxidants) RN - 0 (Flavanones) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NFE2L2 protein, human) RN - 0 (Plant Extracts) RN - 0 (RNA, Small Interfering) RN - 49QAH60606 (baicalein) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.14.14.18 (HMOX1 protein, human) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (MAPK1 protein, human) RN - EC 2.7.11.24 (MAPK3 protein, human) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM MH - Antioxidants/isolation & purification/*pharmacology MH - Cell Line MH - Flavanones/isolation & purification/*pharmacology MH - Gene Expression Regulation MH - Heme Oxygenase-1/genetics/metabolism MH - Humans MH - Hydrogen Peroxide/antagonists & inhibitors/*pharmacology MH - Melanocytes/*drug effects/metabolism/pathology MH - Mitochondria/drug effects/metabolism MH - Mitogen-Activated Protein Kinase 1/genetics/metabolism MH - Mitogen-Activated Protein Kinase 3/genetics/metabolism MH - NF-E2-Related Factor 2/antagonists & inhibitors/*genetics/metabolism MH - Oxidative Stress MH - Phosphatidylinositol 3-Kinases/genetics/metabolism MH - Plant Extracts/chemistry MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - RNA, Small Interfering/genetics/metabolism MH - Scutellaria baicalensis/chemistry MH - Signal Transduction/*drug effects/genetics MH - Vitiligo/genetics/metabolism/pathology OTO - NOTNLM OT - Baicalein OT - Melanocytes OT - Mitochondria OT - Nrf2 OT - Vitiligo EDAT- 2018/10/21 06:00 MHDA- 2019/09/29 06:00 CRDT- 2018/10/21 06:00 PHST- 2018/05/30 00:00 [received] PHST- 2018/08/26 00:00 [revised] PHST- 2018/10/09 00:00 [accepted] PHST- 2018/10/21 06:00 [pubmed] PHST- 2019/09/29 06:00 [medline] PHST- 2018/10/21 06:00 [entrez] AID - S0891-5849(18)32194-4 [pii] AID - 10.1016/j.freeradbiomed.2018.10.421 [doi] PST - ppublish SO - Free Radic Biol Med. 2018 Dec;129:492-503. doi: 10.1016/j.freeradbiomed.2018.10.421. Epub 2018 Oct 18.