Nrf2–Keap1 pathway–mediated effects of resveratrol on oxidative stress and apoptosis in hydrogen peroxide–treated rheumatoid arthritis fibroblast‐like synoviocytes

Zhang, Ye; Wang, Gaoyuan; Wang, Taorong; Cao, Weimin; Zhang, Lixia; Chen, Xiaoyu

doi:10.1111/nyas.14196

Cited by 80 publications

(53 citation statements)

References 58 publications

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“…Our data show that resveratrol down‐regulated the levels of p65‐NF‐κB protein expression in AIA animals similar to other studies, which demonstrated that resveratrol suppresses inflammation by down‐regulating NF‐κB activation. [ 40,44 ] Remarkably, our data described a strong positive correlation between p62 and p65‐NF‐κB. In this sense, it has been described how NF‐κB induces expression of p62 and as defective autophagy results in accumulation of p62, which can activate NF‐κB.…”

Section: Discussionsupporting

confidence: 67%

Autophagy Activation by Resveratrol Reduces Severity of Experimental Rheumatoid Arthritis

Fernández-Rodríguez

Almonte-Becerril

Ramil-Gómez

et al. 2020

Molecular Nutrition Food Res

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Scope Previous work reported that dietary supplementation with resveratrol lowers synovial hyperplasia, inflammatory and oxidative damage in an antigen‐induced arthritis (AIA) model. Here, it is investigated whether resveratrol can regulate the abnormal synovial proliferation by inducing autophagy and controlling the associated inflammatory response. Methods and results Animals treated with resveratrol 8 weeks before AIA induction show the highest significant signal for microtubule‐associated protein 1 light chain 3 by confocal microscopy. Besides, resveratrol significantly reduces p62 expression, but it does not increase the signal of beclin‐1. Also, active caspase‐3 expression, as well as poly(ADP‐ribose) polymerase, is upregulated in the AIA group, and is significantly reduced in resveratrol‐treated AIA group. Resveratrol also mitigates angiopoietin‐1 and vascular endothelial growth factor signals. Finally, resveratrol significantly reduces the serum levels of IL‐1β, C reactive protein, and prostaglandin E2, as well as nuclear factor κB synovial tissue expression, which shows a significant correlation with p62 expression. Conclusion Dietary supplementation with resveratrol induces the noncanonical autophagy pathway and limits the cross‐talk with inflammation, which in consequence modulates the synovial hyperplasia. Preventive strategies that incorporate dietary intervention with resveratrol may offer a potential therapeutic alternative to drugs to influence the risk of rheumatoid arthritis and influence its course.

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Section: Discussionsupporting

confidence: 67%

Autophagy Activation by Resveratrol Reduces Severity of Experimental Rheumatoid Arthritis

Fernández-Rodríguez

Almonte-Becerril

Ramil-Gómez

et al. 2020

Molecular Nutrition Food Res

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“…Resveratrol may be able to suppress the proinflammatory activity and may be potent in treating metabolic disorders that usually are associated with PCOS [27]. Furthermore, experimental evidence has demonstrated a protective effect of resveratrol against several conditions mediated by OS [28]. Thus, we undertook to examine the effect of resveratrol on protection of PCOS rats from ovarian fibrosis mediated by p66Shc-induced OS.…”

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confidence: 99%

Suppression of p66Shc prevents hyperandrogenism-induced ovarian oxidative stress and fibrosis

Wang

et al. 2020

J Transl Med

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Background: Rats with hyperandrogen-induced polycystic ovary syndrome (PCOS) have been shown to develop ovarian oxidative stress (OS) and fibrosis. The Sirt1 agonist, resveratrol, can reduce OS through inhibiting p66Shc in other models of OS. Methods: We created a rat PCOS model with increased OS levels following treatment with one of the two androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT). The PCOS related features were determined by measurement of malondialdehyde (MDA) and superoxide dismutase (SOD) levels or by examining the reactive oxygen species (ROS) levels using the DCF-DA probe. The potential mechanisms by which p66Shc/Sirt1 mediates ovarian fibrosis were explored by western blotting, quantitative reverse transcription-PCR, immunofluorescence staining, and immunohistochemistry. Results: Hyperandrogen dramatically augmented OS and activation of fibrotic factors in the ovary. Our data demonstrated that treatment with resveratrol enhanced Sirt1 and decreased ovarian OS as well as inhibited phosphorylation of p66Shc both in vivo and in vitro. The treatment suppressed fibrotic factor activation and improved ovarian morphology. Lentivirus-or siRNA-mediated p66Shc knockdown resulted in a dramatic enhancement of Sirt1 expression, down-regulation of ROS and suppression of fibrotic factors in granulosa cells. Moreover, p66Shc overexpression markedly increased the expression of fibrotic factors. Additionally, silencing Sirt1 induced a dramatic increase in p66Shc and enhanced activation of fibrotic factors. Conclusions: p66Shc may be a direct target of Sirt1 for inducing ROS and thus promoting fibrosis. Further exploration of the mechanisms of p66Shc in both fibrosis and OS may provide novel therapeutic strategies that will facilitate the improvement in PCOS symptoms and reproductive functions.

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“…As a consequence, the body generates an oxidative stress response to promote cell apoptosis, though pathological injury may still result (32). It is established that the ROS-mediated oxidative stress is a key inducer of cell apoptosis (33). ROS may also serve as a messenger in cells that is able to promote the activation of apoptosis to indirectly cause cell injury (34).…”

Section: Discussionmentioning

confidence: 99%

Protective functions of Lycium barbarum polysaccharides in H2O2‑injured vascular endothelial cells through anti‑oxidation and anti‑apoptosis effects

Xue

Zhu

et al. 2019

biom rep

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Cell injury in the cardiovascular endothelia caused by oxidative stress is among the major inducers of endothelium dysfunction and serves an important role in initiating cardiovascular diseases (CVDs). Therefore, protecting and improving the normal function of endothelial cells are considered key measures against CVDs. As a traditional Chinese medicinal component, Lycium barbarum is regarded to have high medicinal value. The present study aimed to investigate the potential anti-apoptosis and anti-oxidation effects of Lycium barbarum polysaccharides (LBPs) on injured rat artery endothelial cells, to demonstrate the experimental and medicinal values of LBPs. In the present study, the aortic endothelial cells of rats were cultivated and randomly divided into five groups: A control group, H2O2-injured group (H2O2 group), H2O2+LBPs (110 µg/ml) group (low-dose group, LT), H2O2+LBPs (220 µg/ml) group (medium-dose group, MT) and H2O2+LBPs (440 µg/ml) group (high-dose group, HT). Among these, the activity of superoxide dismutase (SOD), and the levels of malondialdehyde (MDA) and nitric oxide (NO) were detected by colorimetry. Additionally, the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected by western blotting. It was observed that SOD activity and NO content decreased while MDA content increased significantly in the H2O2 group (P<0.05 vs. control); that SOD activity in the MT and HT group, and NO content in all three LBP groups were increased, while MDA content in the three LBP groups was decreased, compared with the H2O2 group (all P<0.05); that Bcl-2 expression decreased significantly in the H2O2 group while the expression of Bax increased significantly compared with the control group (both P<0.05); and that Bcl-2 expression in all three LBP groups increased, while Bax expression in the MT and HT groups decreased compared with the H2O2 group (all P<0.05), with these altered Bax levels being statistically similar to those in the control group (P>0.05). On light microscopy, the cells in the control group exhibited spindle-shaped morphology, consistent sizes, defined boundaries, and distinct nuclei of equivalent sizes with round or oval morphology. Additionally, the chromatin in the nuclei was evenly distributed, and all cells were adhered in a paving-stone arrangement. Notably, only few cells died. Conversely, the cells in the H2O2 group exhibited signs of damage and enlarged gaps, and focal cells died. In the HT group, the cells once again appeared adherent and exhibited similar morphological status to the normal cells. Overall, these results indicate that LBPs serve a protective role in oxidative-injured vascular endothelial cells through anti-apoptosis and anti-oxidation effects.

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Nrf2–Keap1 pathway–mediated effects of resveratrol on oxidative stress and apoptosis in hydrogen peroxide–treated rheumatoid arthritis fibroblast‐like synoviocytes

Cited by 80 publications

References 58 publications

Autophagy Activation by Resveratrol Reduces Severity of Experimental Rheumatoid Arthritis

Autophagy Activation by Resveratrol Reduces Severity of Experimental Rheumatoid Arthritis

Suppression of p66Shc prevents hyperandrogenism-induced ovarian oxidative stress and fibrosis

Protective functions of Lycium barbarum polysaccharides in H2O2‑injured vascular endothelial cells through anti‑oxidation and anti‑apoptosis effects

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