The in vitro and in vivo depigmenting activity of pterostilbene through induction of autophagy in melanocytes and inhibition of UVA-irradiated α-MSH in keratinocytes via Nrf2-mediated antioxidant pathways

Hseu, You‐Cheng; Gowrisankar, Yugandhar Vudhya; Wang, Liwei; Zhang, Yanzhen; Chen, Xuan-Zao; Huang, Pei-Jane; Yen, Hung-Rong; Yang, Hsin‐Ling

doi:10.1016/j.redox.2021.102007

Cited by 57 publications

(41 citation statements)

References 54 publications

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“…We previously proved that PS’s remarkable antioxidative properties ameliorate UVA‐induced skin damage [29]. Here, we demonstrated that PS not only preventively but also therapeutically improved pulmonary allergic airway inflammation.…”

Section: Discussionmentioning

confidence: 54%

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Targeting glycolysis in Th2 cells by pterostilbene attenuates clinical severities in an asthmatic mouse model and IL‐4 production in peripheral blood from asthmatic patients

Liu

Song

et al. 2022

Immunology

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Asthma, a major non‐communicable disease, affects both adults and children and is associated with high morbidity compared with other chronic diseases. The glycolysis‐associated activation of type 2 helper T (Th2) cells is the critical immunopathological mechanism involved in asthma deterioration. Long‐term use of steroids as a medical treatment for asthma induces side effects and resistance. Pterostilbene (PS), a stilbenoid compound found in blueberry and vines, exhibits antihyperglycemic and anti‐inflammatory properties. Thus, we hypothesized that the modulation of T cell immunity by PS may be an applicable intervention to treat asthma. Airway hyperresponsiveness, interleukin (IL)‐4 and IL‐13 levels, IgE, IgG, pulmonary infiltrated monocytes and eosinophils, and mucosubstances were measured in house dust mite (HDM)‐induced asthmatic mice under PS treatment. Bioenergetic metabolism, PI3K‐mTOR signalling, GATA3 expression and histone acetylation in PS‐treated Th2 cells were investigated. PS improved HDM‐induced pulmonary allergic airway inflammation by inhibiting Th2 cell and eosinophil accumulation in HDM asthmatic mice both in the preventive and therapeutic models. Targeting glycolysis resulted in IL‐4 inhibition via the downregulation of mTOR, GATA3 and histone acetylation in PS‐treated Th2 cells. Glucose supplementation reversed the inhibitory effect of PS on Th2 cells in vitro. Adoptive transfer with glucose‐treated Th2 cells enhanced Th2 activation and eosinophilic accumulation in PS‐treated asthmatic mice. Furthermore, PS significantly inhibited IL‐4 production of CD4+ T cells from the peripheral blood mononuclear cells of patients with asthma. PS attenuates HDM‐induced asthma via the inhibition of the Glut1/mTOR/GATA3 axis in Th2 cells, which supports the potential pharmaceutical application of PS treatment for asthma.

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Section: Discussionmentioning

confidence: 54%

“…We previously proved that PS's remarkable antioxidative properties ameliorate UVA-induced skin damage [29].…”

Section: Discussionmentioning

confidence: 99%

Targeting glycolysis in Th2 cells by pterostilbene attenuates clinical severities in an asthmatic mouse model and IL‐4 production in peripheral blood from asthmatic patients

Liu

Song

et al. 2022

Immunology

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“…Evidences show that both autophagy and apoptosis are tightly regulated by Nrf2 [ 65 , 66 ]. In addition, Nrf2 plays a pivotal role in the development of DCM.…”

Section: Discussionmentioning

confidence: 99%

Soluble Epoxide Hydrolase Inhibition Protected against Diabetic Cardiomyopathy through Inducing Autophagy and Reducing Apoptosis Relying on Nrf2 Upregulation and Transcription Activation

Fang

Liu

Ding

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Many patients with diabetes die from diabetic cardiomyopathy (DCM); however, effective strategies for the prevention or treatment of DCM have not yet been clarified. Methods. Leptin receptor-deficient (db/db) mice were treated with either the soluble epoxide hydrolase (sEH) inhibitor AUDA or vehicle alone. A virus carrying Nrf2 shRNA was used to manipulate Nrf2 expression in db/db mice. Cardiac structures and functions were analyzed using echocardiography and hemodynamic examinations. Primary cardiomyocytes cultured under high glucose and high fat (HGHF) conditions were used to conduct in vitro loss-of-function assays after culture in the presence or absence of AUDA (1 μM). Fluorescence microscopy-based detection of mCherry-GFP-LC3 was performed to assess autophagic flux. Results. The sEH inhibitor AUDA significantly attenuated ventricular remodeling and ameliorated cardiac dysfunction in db/db mice. Interestingly, AUDA upregulated Nrf2 expression and promoted its nuclear translocation in db/db mice and the HGHF-treated cardiomyocytes. Additionally, AUDA increased autophagy and decreased apoptosis in db/db mice heart. Furthermore, the administration of AUDA promoted autophagic flux and elevated LC3-II protein level in the presence of bafilomycin A1. However, AUDA-induced autophagy was abolished, and the antiapoptotic effect was partially inhibited upon Nrf2 knockdown. Conclusion. Our findings suggest that the sEH inhibitor AUDA attenuates cardiac remodeling and dysfunction in DCM via increasing autophagy and reducing apoptosis, which is relevant to activate Nrf2 signaling pathway.

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“…The activation of NF-E2-related factor 2 (NRF2) is a mechanism of 11αOH-KA-mediated suppression of TYR gene expression [ 29 ]. However, NRF2 has been reported to suppress MITF gene expression [ 30 , 31 ], leading to the downregulation of TYR and TYRP-1. There evidences suggest that in addition to NRF2, an unknown factor associated with MITF in the promoter may contribute to TYR-specific transcription, which may be also the case for GIF-2209.…”

Section: Discussionmentioning

confidence: 99%

GIF-2209, an Oxindole Derivative, Accelerates Melanogenesis and Melanosome Secretion via the Modification of Lysosomes in B16F10 Mouse Melanoma Cells

et al. 2021

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Melanogenesis and melanosome secretion are regulated by several mechanisms. In this study, we found that the oxindole derivative GIF-2209 accelerated melanogenesis associated with the discrimination in the expression and intracellular distributions of two melanogenic enzymes, tyrosinase (TYR) and tyrosinase-related protein-1 (TYRP-1). GIF-2209 upregulated the expression of TYR via a microphthalmia transcription factor (MITF)-independent mechanism, leading to high expression of protein. In contrast, GIF-2209 did not alter the mRNA levels of TYRP-1 and suppressed its protein levels. GIF-2209 induced the dissociation of TYR from TYRP-1 but did not alter the association between TYR and CD63, a melanosome and lysosome marker. The protein levels of CD63 were also upregulated by GIF-2209. GIF-2209 induced lysosome expansion and redistribution in all areas of the cytosol, accompanied by autophagy acceleration (upregulation of LC3BII protein levels and downregulation of p62 protein levels). In addition, GIF-2209 stimulated the secretion of melanosomes containing high levels of TYR, TYRP-1, and CD63 proteins. The GIF-2209 mediated melanosome secretion was sensitive to the lysosome inhibitor chloroquine. These results suggest that GIF-2209 may activate lysosomal functions with TYR gene expression, while it accelerates melanosome secretion, which finally leads to the depletion of intracellular melanogenic enzyme, especially TYRP-1 protein.

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The in vitro and in vivo depigmenting activity of pterostilbene through induction of autophagy in melanocytes and inhibition of UVA-irradiated α-MSH in keratinocytes via Nrf2-mediated antioxidant pathways

Cited by 57 publications

References 54 publications

Targeting glycolysis in Th2 cells by pterostilbene attenuates clinical severities in an asthmatic mouse model and IL‐4 production in peripheral blood from asthmatic patients

Targeting glycolysis in Th2 cells by pterostilbene attenuates clinical severities in an asthmatic mouse model and IL‐4 production in peripheral blood from asthmatic patients

Soluble Epoxide Hydrolase Inhibition Protected against Diabetic Cardiomyopathy through Inducing Autophagy and Reducing Apoptosis Relying on Nrf2 Upregulation and Transcription Activation

GIF-2209, an Oxindole Derivative, Accelerates Melanogenesis and Melanosome Secretion via the Modification of Lysosomes in B16F10 Mouse Melanoma Cells

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