Fisetin Suppresses Pulmonary Inflammatory Responses Through Heme Oxygenase-1 Mediated Downregulation of Inducible Nitric Oxide Synthase

Sim, Hyunchae; Choo, Samyeol; Kim, Jae Hong; Baek, Moon‐Chang; Bae, Jong‐Sup

doi:10.1089/jmf.2020.4755

Cited by 8 publications

(6 citation statements)

References 19 publications

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“…Our results showed that fisetin remarkably enhanced the expression and phosphorylation of Nrf2 as well as its expression in the nucleus in H 2 O 2 -treated ARPE-19 cells. Fisetin also improved the expression and enzymatic activity of HO-1, suggesting that fisetin was able to activate the Nrf2/AREs pathway, which was in good agreement with previous findings ( Hanneken et al, 2006 ; Sim et al, 2020 ; Jiang et al, 2021 ; Li et al, 2022 ). However, the ROS scavenging activity and viability-enhancing ability of fisetin were significantly abolished by blocking HO-1 activity via a HO-1 antagonist ZnPP.…”

Section: Discussionsupporting

confidence: 92%

“…Certain intracellular signaling pathways are involved in defense strategies against oxidative stress, and there is growing evidence that the Nrf2/AREs pathway is involved in the antioxidant activity of fisetin in multiple cell lines ( Sim et al, 2020 ; Jiang et al, 2021 ; Li et al, 2022 ). There is growing evidence that Nrf2 is an effective target in the regulation of oxidative stress-related retinal degeneration.…”

Section: Discussionmentioning

confidence: 99%

“…More interestingly, although excessive accumulation of ROS may be a major factor in fisetin-induced apoptosis of cancer cells ( Su et al, 2017 ; Tsai et al, 2019 ; Imran et al, 2021 ), the protective effects of fisetin against cell damage to various stimuli are associated with potent antioxidant activity by acting as a potent ROS scavenger ( Zhao et al, 2019 ; Rodius et al, 2020 ; Molagoda et al, 2021 ; Ding et al, 2022 ). Moreover, several previous studies have demonstrated that this compound can modulate the Nrf2/antioxidant response elements (AREs) pathway to exert antioxidant activity ( Sim et al, 2020 ; Jiang et al, 2021 ; Li et al, 2022 ). Although Hanneken et al ( Hanneken et al, 2006 ) have suggested that the antioxidant activity of fisetin in RPE cells could be related to an increased expression of Nrf2 and HO-1, one of the representative downstream factors of Nrf2, the role of this pathway in the antioxidant activity of fisetin in RPE cells is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Fisetin Attenuated Oxidative Stress-Induced Cellular Damage in ARPE-19 Human Retinal Pigment Epithelial Cells Through Nrf2-Mediated Activation of Heme Oxygenase-1

et al. 2022

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Fisetin is a kind of bioactive flavonol, widely present in various fruits such as strawberries and apples, and is known to act as a potent free radical scavenger. However, the mechanism of action related to the antioxidant activity of this compound in human retinal pigment epithelial (RPE) cells is not precisely known. In this study, we aimed to investigate whether fisetin could attenuate oxidative stress-induced cytotoxicity on human RPE ARPE-19 cells. To mimic oxidative stress, ARPE-19 cells were treated with hydrogen peroxide (H2O2), and fisetin significantly inhibited H2O2-induced loss of cell viability and increase of intracellular reactive oxygen species (ROS) production. Fisetin also markedly attenuated DNA damage and apoptosis in H2O2-treated ARPE-19 cells. Moreover, mitochondrial dysfunction in H2O2-treated cells was alleviated in the presence of fisetin as indicated by preservation of mitochondrial membrane potential, increase of Bcl-2/Bax expression ratio, and suppression of cytochrome c release into the cytoplasm. In addition, fisetin enhanced phosphorylation and nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2), which was associated with increased expression and activity of heme oxygenase-1 (HO-1). However, the HO-1 inhibitor, zinc protoporphyrin, significantly reversed the protective effect of fisetin against H2O2-mediated ARPE-19 cell injury. Therefore, our results suggest that Nrf2-mediated activation of antioxidant enzyme HO-1 may play an important role in the ROS scavenging activity of fisetin in RPE cells, contributing to the amelioration of oxidative stress-induced ocular disorders.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fisetin Attenuated Oxidative Stress-Induced Cellular Damage in ARPE-19 Human Retinal Pigment Epithelial Cells Through Nrf2-Mediated Activation of Heme Oxygenase-1

et al. 2022

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“…FIS is a novel dietary agent present in a range of plants, fruits, and vegetables. FIS improves pulmonary inflammation by downregulating the p-STAT-1 and NF-κB signaling pathways via heme oxygenase-1 ( 146 ). It can effectively alleviate pulmonary oxidative stress induced by strong oxidants ( 147 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms of alveolar epithelial cell senescence and idiopathic pulmonary fibrosis: a narrative review

Tu¹,

Wei²,

Jia³

et al. 2023

J Thorac Dis

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Background and Objective: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia of unknown etiology. An increasing number of studies have reported that the incidence of IPF increases with age. Simultaneously, the number of senescent cells increased in IPF. Epithelial cell senescence, an important component of epithelial cell dysfunction, plays a key role in IPF pathogenesis. This article summarizes the molecular mechanisms associated with alveolar epithelial cell senescence and recent advances in the applications of drugs targeting pulmonary epithelial cell senescence to explore novel therapeutic approaches for the treatment of pulmonary fibrosis.Methods: All literature published in English on PubMed, Web of Science, and Google Scholar were electronically searched online using the following keyword combinations: aging, alveolar epithelial cell, cell senescence, idiopathic pulmonary fibrosis, WNT/β-catenin, phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), mammalian target of rapamycin (mTOR), and nuclear factor kappa B (NF-κB).

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“…The anti-inflammatory role of HO-1 is facilitated via the suppression of several proinflammatory mediators and cytokines [9]. Several studies established that HO-1 and its products, such as CO, inhibit the protein expression of iNOS, reducing NO production [10]. The expression of HO-1 is associated with several signaling pathways, such as mitogenactivated protein kinases (MAPKs) and the transcription factor nuclear factor-E2-related factor 2 (Nrf2) [11].…”

Section: Introductionmentioning

confidence: 99%

Involvement of Antioxidant Defenses and NF-κB/ERK Signaling in Anti-Inflammatory Effects of Pterostilbene, a Natural Analogue of Resveratrol

Jayakumar

Sheu

et al. 2021

Applied Sciences

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Pterostilbene (PTE), a natural stilbenoid occurring in grapes and berries, is recognized as a dimethylated analogue of resveratrol. This compound shows numerous notable pharmacological activities, including antiaging, anticancer, antidiabetes, antioxidant, and neuroprotection. This study investigates the anti-inflammatory properties of PTE in macrophage cells (RAW 264.7) against the lipoteichoic acid (LTA) stimulation. The expression of inflammatory tumor necrosis factor (TNF-α), interleukin-1β (IL-1 β), and inducible nitric oxide synthase (iNOS) and the content of nitric oxide (NO) were detected in LTA-induced cells. In addition, a Western blot assay was used to detect mitogen-activated protein kinases: extracellular signal-regulated kinase (ERK)1/2, p38 MAPK, and c-Jun N-terminal kinase (JNK). The phosphorylation of IκB and p65 and translocation of nuclear factor kappa B (NF-κB) were assessed by Western blot and immuno-fluorescence staining. The results showed that PTE significantly attenuated NO production and TNF-α, IL-1 β, and iNOS expression in LTA stimulated cells. Among the activation of ERK, JNK, and p38 in cells treated with LTA, PTE at higher concentration had only inhibited ERK activation. However, PTE blocked IκB phosphorylation, phosphorylation and nuclear translocation of p65NF-κB. Fascinatingly, PTE enhanced antioxidant defense molecules as verified by the enhanced heme oxygenase-1 (HO-1) expression, catalase (CAT) antioxidant enzyme, and non-enzymatic antioxidant, and reduced glutathione (GSH) in LTA-induced RAW 264.7 cells. These results suggest that PTE exerts an anti-inflammatory property via attenuating NF-κB/ERK signaling pathways as well as enriching antioxidant defense mechanisms.

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Fisetin Suppresses Pulmonary Inflammatory Responses Through Heme Oxygenase-1 Mediated Downregulation of Inducible Nitric Oxide Synthase

Cited by 8 publications

References 19 publications

Fisetin Attenuated Oxidative Stress-Induced Cellular Damage in ARPE-19 Human Retinal Pigment Epithelial Cells Through Nrf2-Mediated Activation of Heme Oxygenase-1

Fisetin Attenuated Oxidative Stress-Induced Cellular Damage in ARPE-19 Human Retinal Pigment Epithelial Cells Through Nrf2-Mediated Activation of Heme Oxygenase-1

Molecular mechanisms of alveolar epithelial cell senescence and idiopathic pulmonary fibrosis: a narrative review

Involvement of Antioxidant Defenses and NF-κB/ERK Signaling in Anti-Inflammatory Effects of Pterostilbene, a Natural Analogue of Resveratrol

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