Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice

Wu, Po-Yuan; Lyu, Jia-Ling; Liu, Yi-Jung; Chien, Ting-Yi; Hsu, Hao-Cheng; Wen, Kuo‐Ching; Chiang, Hsiu-Mei

doi:10.3390/ijms18102118

Cited by 52 publications

(44 citation statements)

References 39 publications

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“…At the end of the experiment, the exposed areas were excised and then immersed in 10% formaldehyde in the PBS. The slides were mounted with a coverslip, stained in hematoxylin and eosin or Masson’s trichrome, and examined under a microscope or applied for immunohistological analysis as previously described [23].…”

Section: Methodsmentioning

confidence: 99%

Protective Effects of Sesamin against UVB-Induced Skin Inflammation and Photodamage In Vitro and In Vivo

Lin

Hou

et al. 2019

Biomolecules

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Ultraviolet (UV) exposure has been demonstrated as the most critical factor causing extrinsic skin aging and inflammation. This study explored the protective effects and mechanisms of sesamin against skin photodamage. Sesamin reduced intracellular reactive oxygen species production after UVB irradiation in human dermal fibroblasts. The sesamin treatment attenuated mitogen-activated protein (MAP) kinase phosphorylation and matrix metalloproteinase (MMPs) overexpression induced by UVB exposure, and it significantly enhanced the tissue inhibitor of metalloproteinase-1 protein expression. Sesamin also elevated the total collagen content in human fibroblasts by inhibiting UVB-induced mothers against decapentaplegic homolog 7 (Smad7) protein expression. Sesamin reduced UVB-induced inducible nitric oxide synthase (i-NOS) and cyclooxygenase-2 (COX-2) overexpression and inhibited nuclear factor-kappa B (NF-κB) translocation. Moreover, sesamin may regulate the c-Jun N-terminal kinases (JNK) and p38 MAP kinase pathways, which inhibit COX-2 expression. Sesamin could reduce UVB-induced inflammation, epidermal hyperplasia, collagen degradation, and wrinkle formation in hairless mice. It also reduced MMP-1, interleukin (IL-1), i-NOS, and NF-κB in the mouse skin. These results demonstrate that sesamin had antiphotodamage and anti-inflammatory activities. Sesamin has potential for use as a skin protection agent in antiphotodamage and skin care products.

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Section: Methodsmentioning

confidence: 99%

Protective Effects of Sesamin against UVB-Induced Skin Inflammation and Photodamage In Vitro and In Vivo

Lin

Hou

et al. 2019

Biomolecules

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“…Fisetin also inhibited aflatoxin-B1-induced hepatocellular carcinoma via the downmodulation of oxidative stress and inflammation in rats (Maurya & Trigun, 2016). The tropical application of fisetin prevented UVB-induced inflammation and oxidative stress during skin damage in hairless mice and human lens epithelial cells, respectively (Wu et al, 2017;Yao, Zhang, Zhang, Ye, & Zhu, 2008).…”

Section: Discussionmentioning

confidence: 97%

“…Recently, Nrf2-ARE signalling was proposed as a master regulator of cellular antioxidant activity (Zhang et al, 2019). Similarly, a number of previous studies have shown that fisetin blocks oxidative stress by augmenting the expression of Nrf2 as well as its target antioxidant gene, unravelling the mechanism through which fisetin exerts its antioxidant actions (Lee et al, 2011;Wu et al, 2017;Zhang, Wang, Zhou, Zhu, & Fei, 2018). In agreement with this, we found the increased expression of Nrf2 as well as that of its target genes HO-1 and Gpx-2 in fisetin-treated CS-exposed rats.…”

Section: Discussionmentioning

confidence: 99%

“…Fisetin also inhibited aflatoxin‐B1‐induced hepatocellular carcinoma via the downmodulation of oxidative stress and inflammation in rats (Maurya & Trigun, ). The tropical application of fisetin prevented UVB‐induced inflammation and oxidative stress during skin damage in hairless mice and human lens epithelial cells, respectively (Wu et al, ; Yao, Zhang, Zhang, Ye, & Zhu, ). Fisetin is widely recognized as a cardioprotective agent due to its ability to increase NO bioavailability, induce antioxidant gene expression, and mitigate inflammation (Zhang, Du, Wei, Wang, & Shen, ).…”

Section: Discussionmentioning

confidence: 99%

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The plant flavonoid, fisetin alleviates cigarette smoke‐induced oxidative stress, and inflammation in Wistar rat lungs

et al. 2019

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In the present study, we tested the antioxidant and anti‐inflammatory potential of the plant flavonoid, fisetin against cigarette smoke‐induced oxidative stress, and inflammation in rat lungs. Male Wistar rats were chronically exposed to cigarette smoke (CS) with or without administration of fisetin. Fisetin administration to CS‐exposed rats resulted in a significant reduction in neutrophils and macrophages in bronchoalveolar lavage fluid as well as malondialdehyde, 3‐nitrotyrosine, 8‐isoprostane, tumor necrosis factor‐alpha, interleukin‐1beta, granulocyte macrophage‐colony stimulating factor, interleukin‐4, and interleukin‐10 levels in lung tissues compared to those in CS‐exposed rats not treated with fisetin. Fisetin also significantly augmented lung hemoxinase‐1, glutathione peroxidase‐2, reduced glutathione, superoxide dismutase, nitric oxide, and nuclear factor erythroid 2‐related factor (Nrf2) levels in CS‐exposed rats. In addition, a marked reversal in CS‐induced histopathological changes was noted in fisetin‐treated rats. Collectively, these data demonstrate the potential of fisetin to blunt CS‐induced oxidative stress and inflammation in the lung and to prevent tissue damage via the Nrf2‐mediated upregulation of antioxidant gene expression. Practical applications In the present study, we found that the plant flavonoid, fisetin significantly abrogated the oxidative stress, inflammation, and tissue damage induced by cigarette smoke, a powerful pro‐oxidant in rat lungs. Additionally, fisetin markedly reversed cigarette smoke‐induced increases in neutrophil and macrophage cell populations in bronchoalveolar lavage fluid. These findings are particularly significant considering the association of cigarette smoking with increased oxidative stress and inflammation, which are central to the pathologies of a wide variety of chronic diseases including chronic obstructive pulmonary disease, cancer, and cardiovascular diseases. Therefore, the present work underscores the beneficial effects of the regular consumption of plant‐based foods with medicinal properties for the effective prevention of these chronic diseases.

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“…The mice were macroscopically observed, and their ears were excised, fixed in 10% formaldehyde, and embedded in paraffin. The skin slides were stained with H&E. Collagen in the skin sections was stained with Masson trichrome and was examined under a microscope, as previously described [24,25].…”

Section: Methodsmentioning

confidence: 99%

Sesamol Inhibited Ultraviolet Radiation-Induced Hyperpigmentation and Damage in C57BL/6 Mouse Skin

You

Liu

et al. 2019

Antioxidants

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Melanin is synthesized through a series of oxidative reactions initiated with tyrosine and catalyzed by melanogenesis-related proteins such as tyrosinase, tyrosinase-related protein-1 (TRP-1), dopachrome tautomerase (TRP-2), and microphthalmia-associated transcription factor (MITF). Our previous study demonstrated that sesamol inhibited melanin synthesis through the inhibition of the melanocortin 1 receptor (MC1R)/MITF/tyrosinase pathway in B16F10 cells. In this study, sesamol was applied to C57BL/6 mouse skin to understand its activity with respect to skin pigmentation. The results indicated that ultraviolet (UV) B-induced hyperpigmentation in the C57BL/6 mouse skin was significantly reduced by topical application of sesamol for 4 weeks. Sesamol reduced the melanin index and melanin content of the skin. In addition, sesamol elevated the brightness (L* value) of the skin. Sesamol also reduced UVB-induced hyperplasia of epidermis and collagen degradation in dermis. In immunohistochemical staining, topical application of sesamol reduced UVB-induced tyrosinase, TRP-1, TRP-2, and MITF expression in the epidermis of the skin. These results demonstrated that sesamol is a potent depigmenting agent in the animal model.

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Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice

Cited by 52 publications

References 39 publications

Protective Effects of Sesamin against UVB-Induced Skin Inflammation and Photodamage In Vitro and In Vivo

Protective Effects of Sesamin against UVB-Induced Skin Inflammation and Photodamage In Vitro and In Vivo

The plant flavonoid, fisetin alleviates cigarette smoke‐induced oxidative stress, and inflammation in Wistar rat lungs

Sesamol Inhibited Ultraviolet Radiation-Induced Hyperpigmentation and Damage in C57BL/6 Mouse Skin

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