Aloe emodin relieves Ang II-induced endothelial junction dysfunction via promoting ubiquitination mediated NLRP3 inflammasome inactivation

Zhang, Yi; Song, Ziqing; Huang, Shan; Zhu, Liangru; Liu, Tianyi; Shu, Hongyan; Wang, Lei; Huang, Yi; Chen, Yang

doi:10.1002/jlb.3ma0520-582r

Cited by 18 publications

(11 citation statements)

References 29 publications

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“…Yu et al (2019) findings indicated that AE can protect against myocardial infarction via the upregulation of miR-133, inhibition of ROS production and suppression of caspase-3 apoptotic signaling pathway. Zhang et al (2020) results revealed that inhibiting the activation of NLRP3 inflammasome and reducing the release of HMGB1 by promoting NLRP3 ubiquitination, thereby restoring the endothelial tight junction proteins and permeability, which indicated that AE exhibited immense potential therapeutic value in hypertensionrelated cardiovascular disease and the development of innovative drugs ( Table 3).…”

Section: Emodin Derivativesmentioning

confidence: 99%

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Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

Gao

Pang

et al. 2020

Front. Pharmacol.

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Emodin is a natural occurring anthraquinone derivative isolated from roots and barks of numerous plants, molds, and lichens. It is found to be an active ingredient in different Chinese herbs including Rheum palmatum and Polygonam multiflorum, and it is a pleiotropic molecule with diuretic, vasorelaxant, anti-bacterial, anti-viral, antiulcerogenic, anti-inflammatory, and anti-cancer effects. Moreover, emodin has also been shown to have a wide activity of anti-cardiovascular diseases. It is mainly involved in multiple molecular targets such as inflammatory, anti-apoptosis, anti-hypertrophy, antifibrosis, anti-oxidative damage, abnormal, and excessive proliferation of smooth muscle cells in cardiovascular diseases. As a new type of cardiovascular disease treatment drug, emodin has broad application prospects. However, a large amount of evidences detailing the effect of emodin on many signaling pathways and cellular functions in cardiovascular disease, the overall understanding of its mechanisms of action remains elusive. In addition, by describing the evidence of the effects of emodin in detail, the toxicity and poor oral bioavailability of mice have been continuously discovered. This review aims to describe a timely overview of emodin related to the treatment of cardiovascular disease. The emphasis is to summarize the pharmacological effects of emodin as an anticardiovascular drug, as well as the targets and its potential mechanisms. Furthermore, the treatment of emodin compared with conventional cardiovascular drugs or target inhibitors, the toxicity, pharmacokinetics and derivatives of emodin were discussed.

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Section: Emodin Derivativesmentioning

confidence: 99%

“…Inhibits NLRP3 inflammasome activation and decreases the release of HMGB1 by promoting NLRP3 ubiquitination, and thus restoring the endothelial tight junction proteins and permeability (Zhang et al, 2020)…”

Section: Fundingmentioning

confidence: 99%

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

Gao

Pang

et al. 2020

Front. Pharmacol.

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“…In line with other ndings, our results showed the NLRP3 in ammasome in AMs was signi cantly activated both in NaT-AP rats and CER + LPS-AP mice. Emerging evidence showed that emodin had an inhibitory effect on the activation of NLRP3 in ammasome in myocardial injury combined with cardiovascular dysfunction [38,40,41]. Importantly, the administration of emodin and AYC markedly inhibited AP-associated activation of NLRP3 in ammasome in AMs, which was supported by downregulated expression of NLRP3, ASC, and Caspase1 p10.…”

Section: Discussionmentioning

confidence: 96%

Emodin Ameliorates Acute Pancreatitis-associated Lung Injury Through Inhibiting the Alveolar Macrophages Pyroptosis

Wu¹,

Yao²,

Hu³

et al. 2021

Preprint

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Background: Emodin, one of the most dominant components of the traditional Chinese medicine rhubarb, has been utilized to treat acute pancreatitis (AP). Acute lung injury (ALI) is one of the most common complications of acute pancreatitis, leading to a serious mortality rate. However, the specific mechanism of emodin in the treatment of AP-associated lung injury remains unclear. Therefore, we investigated the protective roles of emodin in AP-ALI and its underlying mechanisms in two clinically relevant experimental AP models.Methods: NaT-AP model in rats was constructed using 3.5% sodium taurocholate, and CER+LPS-AP model in mice was constructed using caerulein combined with Lipopolysaccharide. Animals were divided randomly into sham, AP, Ac‐YVAD‐CMK (caspase-1 specific inhibitor, AYC), and emodin groups. AP-associated lung injury was assessed through H&E staining, inflammatory cytokine levels, and myeloperoxidase activity. Alveolar macrophages (AMs) pyroptosis was evaluated by flow cytometry. In bronchoalveolar lavage fluid, the levels of lactate dehydrogenase and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Pyroptosis-related protein expressions were detected by Western Blot. Results: Emodin, similar to the positive control AYC, significantly alleviated pancreatic and lung damage in rats and mice. Additionally, emodin decreased the pyroptotic rates of AMs, inflammatory cytokines, and the lactate dehydrogenase level. More importantly, the protein expressions of NLRP3, ASC, Caspase1 p10, GSDMD, and GSDMD-NT in AMs were significantly downregulated after emodin intervention. Conclusion: Emodin has a therapeutic effect on AP-associated lung injury, which is at least partially due to the inhibition of NLRP3/Caspase1/GSDMD-mediated AMs pyroptosis signaling ways.

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“…In line with other findings, our results showed the NLRP3 inflammasome in AMs was significantly activated both in NaT-AP rats and CER+LPS-AP mice. Emerging evidence showed that emodin had an inhibitory effect on the activation of NLRP3 inflammasome in myocardial injury combined with cardiovascular dysfunction ( Ye et al, 2019 ; Zhang et al, 2020 ; Dai et al, 2021 ). In addition, Emodin could attenuate LPS-induced ALI through regulating the NLRP3 inflammasome-dependent pyroptosis signaling pathway ( Liu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Emodin Ameliorates Acute Pancreatitis-Associated Lung Injury Through Inhibiting the Alveolar Macrophages Pyroptosis

Yao²,

Hu³

et al. 2022

Front. Pharmacol.

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Objective: To investigate the protective effect of emodin in acute pancreatitis (AP)-associated lung injury and the underlying mechanisms.Methods: NaT-AP model in rats was constructed using 3.5% sodium taurocholate, and CER+LPS-AP model in mice was constructed using caerulein combined with Lipopolysaccharide. Animals were divided randomly into four groups: sham, AP, Ac-YVAD-CMK (caspase-1 specific inhibitor, AYC), and emodin groups. AP-associated lung injury was assessed with H&E staining, inflammatory cytokine levels, and myeloperoxidase activity. Alveolar macrophages (AMs) pyroptosis was evaluated by flow cytometry. In bronchoalveolar lavage fluid, the levels of lactate dehydrogenase and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Pyroptosis-related protein expressions were detected by Western Blot.Results: Emodin, similar to the positive control AYC, significantly alleviated pancreas and lung damage in rats and mice. Additionally, emodin mitigated the pyroptotic process of AMs by decreasing the level of inflammatory cytokines and lactate dehydrogenase. More importantly, the protein expressions of NLRP3, ASC, Caspase1 p10, GSDMD, and GSDMD-NT in AMs were significantly downregulated after emodin intervention.Conclusion: Emodin has a therapeutic effect on AP-associated lung injury, which may result from the inhibition of NLRP3/Caspase1/GSDMD-mediated AMs pyroptosis signaling pathways.

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Aloe emodin relieves Ang II-induced endothelial junction dysfunction via promoting ubiquitination mediated NLRP3 inflammasome inactivation

Cited by 18 publications

References 29 publications

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

Emodin Ameliorates Acute Pancreatitis-associated Lung Injury Through Inhibiting the Alveolar Macrophages Pyroptosis

Emodin Ameliorates Acute Pancreatitis-Associated Lung Injury Through Inhibiting the Alveolar Macrophages Pyroptosis

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