Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway

Ma, Jingjing; Li, Shuli; Zhu, Longfei; Guo, Sen; Yi, Xiuli; Cui, Tongtong; He, Yide; Chang, Yi‐Lu; Liu, Bangmin; Li, Chunying; Jian, Zhe

doi:10.1016/j.freeradbiomed.2018.10.421

Cited by 75 publications

(45 citation statements)

References 66 publications

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“…BAI has been reported to scavenge intracellular ROS by NRF2-mediated manganese superoxide dismutase and inhibited H 2 O 2 -induced DNA damage and apoptosis [73]. BAI is also known to exert its antioxidative activity through activation of the NRF2-HMOX1 antioxidative system [73][74][75]. In parallel with this, the present study showed that BAI induced the nuclear translocation of NRF2, upregulated the expression of antioxidative enzymes and downregulated the BaP-induced ROS generation in keratinocytes.…”

Section: Discussionsupporting

confidence: 82%

Baicalein Inhibits Benzo[a]pyrene-Induced Toxic Response by Downregulating Src Phosphorylation and by Upregulating NRF2-HMOX1 System

et al. 2020

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Benzo[a]pyrene (BaP), a major environmental pollutant, activates aryl hydrocarbon receptor (AHR), induces its cytoplasmic-to-nuclear translocation and upregulates the production of cytochrome P450 1A1 (CYP1A1), a xenobiotic metabolizing enzyme which metabolize BaP. The BaP-AHR-CYP1A1 axis generates reactive oxygen species (ROS) and induces proinflammatory cytokines. Although the anti-inflammatory phytochemical baicalein (BAI) is known to inhibit the BaP-AHR-mediated CYP1A1 expression, its subcellular signaling remains elusive. In this study, normal human epidermal keratinocytes and HaCaT keratinocytes were treated with BAI, BaP, or BAI + BaP, and assessed for the CYP1A1 expression, antioxidative pathways, ROS generation, and proinflammatory cytokine expressions. BAI and BAI-containing herbal medicine Wogon and Oren-gedoku-to could inhibit the BaP-induced CYP1A1 expression. In addition, BAI activated antioxidative system nuclear factor-erythroid 2-related factor-2 (NRF2) and heme oxygenase 1 (HMOX1), leading the reduction of BaP-induced ROS production. The BaP-induced IL1A and IL1B was also downregulated by BAI. BAI inhibited the phosphorylation of Src, a component of AHR cytoplasmic complex, which eventually interfered with the cytoplasmic-to-nuclear translocation of AHR. These results indicate that BAI and BAI-containing herbal drugs may be useful for inhibiting the toxic effects of BaP via dual AHR-CYP1A1-inhibiting and NRF2-HMOX1-activating activities.

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Section: Discussionsupporting

confidence: 82%

Baicalein Inhibits Benzo[a]pyrene-Induced Toxic Response by Downregulating Src Phosphorylation and by Upregulating NRF2-HMOX1 System

et al. 2020

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“…Phosphorylation of Nrf2 at serine40 has been confirmed to play a key mechanistic role in resisting oxidative stress . It has been proved that BCI possesses the ability to activate Nrf2 signaling pathway in oxidative stress‐related diseases, including vitiligo, neurodegeneration, and cardiomyopathy …”

Section: Introductionmentioning

confidence: 99%

The therapeutic role of baicalein in combating experimental periodontitis with diabetes via Nrf2 antioxidant signaling pathway

Zhao

et al. 2019

J of Periodontal Research

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Background and objective:Oxidative stress has been suggested as an important pathogenic factor contributing to chronic periodontitis with diabetes mellitus (CPDM). Previous studies have revealed the potential therapeutic properties of baicalein (BCI) in oxidative stress-related diseases; however, the antioxidant effects of BCI on therapy for individual with CPDM remain largely unexplored. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in cellular defence against oxidative stress. In this study, we aim to determine whether BCI prevents diabetesrelated periodontal tissue destruction by regulating Nrf2 signaling pathway. Material and methods: Human gingival epithelial cells (hGECs) were challenged with high glucose (HG, 25 mmol/L) and/or lipopolysaccharide (LPS, 20 µg/mL). Reactive oxygen species (ROS) were detected by fluorescence-activated cell sorting. The changes of antioxidant-related genes, including Nrf2, catalase (Cat), glutamatecysteine ligase catalytic subunit (Gclc), superoxide dismutase 1 (Sod1), and superoxide dismutase 2 (Sod2), were quantified by real-time PCR. The localization of phospho-Nrf2 (pNrf2, S40) in the nucleus was detected by immunofluorescence staining and laser scanning confocal microscope (LSCM). PNrf2 and total form of Nrf2 were determined using western blot. The above indicators together with mitochondrial membrane potential (MMP) were further investigated in hGECs pre-treated with different concentrations of BCI (0.01, 0.1, or 0.5 µg/mL) before stimulated with HG plus LPS (GP). Finally, the role of BCI in activating Nrf2 signaling pathway and relieving the alveolar bone absorption was examined in the CPDM model of Sprague Dawley rats.CPDM rats were oral gavaged with BCI (50, 100, or 200 mg/kg daily). The pNrf2 was detected by immunohistochemistry, and the alveolar bone absorption was examined by microcomputed tomography. Results:Our results showed that ROS were significantly increased in both groups of HG and LPS, with the strongest generation in the GP group. In terms of ROSrelated gene expression, we found that the mRNA levels of Nrf2, Cat, Gclc, Sod1, and Sod2 were significantly decreased in HG and LPS groups. In consistent with the strongest induction of ROS in GP group, the gene expression in GP group was further

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“…Hydroxystilbenes are related to resveratrol and have been previously described to reduce the inflammatory response [ 69 ], although not necessarily through the Nrf2 pathway. Based on previous studies that have shown the role of Nrf2 in vitiligo [ 70 , 71 ] and in a variety of other autoimmune diseases (EAE, RA, MS, and psoriasis, reviewed in [ 72 ]), the inventors suggest a role of these compounds against autoimmune diseases through Nrf2 activation. It has been suggested that hydroxystilbenes-related compounds may perturb the Keap1–Nrf2 protein–protein interaction [ 73 ], but this has not yet been clearly documented by mechanistic studies.…”

Section: Resultsmentioning

confidence: 99%

Patent Review (2017–2020) of the Keap1/Nrf2 Pathway Using PatSeer Pro: Focus on Autoimmune Diseases

Chartoumpekis

Ziros

et al. 2020

Antioxidants

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Research on the antioxidant pathway comprising the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and its cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1) is ever increasing. As modulators of this pathway have started to be used in clinical trials and clinical practice, Nrf2 has become the subject of several patents. To assess the patent landscape of the last three years on Nrf2 and evaluate the main fields they refer to, we used the web-based tool PatSeer Pro to identify patents mentioning the Nrf2 pathway between January 2017 and May 2020. This search resulted in 509 unique patents that focus on topics such as autoimmune, neurodegenerative, liver, kidney, and lung diseases and refer to modulators (mainly activators) of the Nrf2 pathway as potential treatments. Autoimmunity emerged as the main theme among the topics of Nrf2 patents, including a broad range of diseases, such as systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, Hashimoto’s thyroiditis, etc.; however, there was a dearth of experimental support for the respective patents’ claims. Given that chronic inflammation is the main element of the pathophysiology of most autoimmune diseases, the majority of patents referring to activation of Nrf2 as a method to treat autoimmune diseases base their claims on the well-established anti-inflammatory role of Nrf2. In conclusion, there is strong interest in securing intellectual property rights relating to the potential use of Nrf2 pathway activators in a variety of diseases, and this trend parallels the rise in related research publications. However, in the case of autoimmunity, more research is warranted to support the potential beneficial effects of Nrf2 modulation in each disease.

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Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway

Cited by 75 publications

References 66 publications

Baicalein Inhibits Benzo[a]pyrene-Induced Toxic Response by Downregulating Src Phosphorylation and by Upregulating NRF2-HMOX1 System

Baicalein Inhibits Benzo[a]pyrene-Induced Toxic Response by Downregulating Src Phosphorylation and by Upregulating NRF2-HMOX1 System

The therapeutic role of baicalein in combating experimental periodontitis with diabetes via Nrf2 antioxidant signaling pathway

Patent Review (2017–2020) of the Keap1/Nrf2 Pathway Using PatSeer Pro: Focus on Autoimmune Diseases

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