Oridonin attenuates hind limb ischemia–reperfusion injury by modulating Nrf2-mediated oxidative stress and NLRP3-mediated inflammation

Zhao, Xiaoqi; Liu, Yutong; Wang, Lei; Yan, Chaolong; Liu, Han; Zhang, Wenxin; Zhao, Hongting; Chen, Cheng; Chen, Zhipeng; Xu, Tianze; Li, Kuanyu; Cai, Jing; Qiao, Tong

doi:10.1016/j.jep.2022.115206

Cited by 10 publications

(13 citation statements)

References 41 publications

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“…Lu et al found oridonin alleviated myocardial ischemia-reperfusion injury by preventing oxidative stress and NLRP3 in ammasome pathway (Lu et al, 2020). In addition, it was con rmed that oridonin exerted protective effects on LPS-induced acute lung injury and hind limb ischemia-reperfusion injury via Nrf2-independent anti-in ammatory and Nrf2-dependent antioxidative activities (Yang et al, 2019;Zhao et al, 2022). This study rstly proves that oridonin prevents atherosclerosis progression by suppressing NLRP3 in ammasome activation and promoting Nrf2 antioxidative stress.…”

Section: Discussionsupporting

confidence: 56%

“…A solution of 1% dimethyl sulfoxide (DMSO) with normal saline was used to dissolve oridonin. The dose of oridonin (10 mg/kg/d and 20 mg/kg/d) was chosen based on previous studies (Lu et al, 2020;Yan et al, 2020;Zhao et al, 2022). The mice were intraperitoneally injected with normal saline or oridonin (10mg/kg or 20mg/kg) daily for 12 weeks from 8 weeks of age.…”

Section: Drug Administrationmentioning

confidence: 99%

“…The natural compound oridonin, derived from the plant Rabdosia Rrubescens, has been studied as a covalent NLRP3 inhibitor (He et al, 2018). Furthermore, it was demonstrated that oridonin exerted protective effects on LPS-induced acute lung injury and hind limb ischemia-reperfusion injury via Nrf2-independent anti-in ammatory and Nrf2-dependent antioxidative activities (Yang et al, 2019;Zhao et al, 2022). However, there is no evidence whether oridonin have a protective effect on atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

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Oridonin attenuates the progression of atherosclerosis by inhibiting NLRP3 and activating Nrf2 in apolipoprotein E-deficient mice

Wang

Zhao

Ding

et al. 2022

Preprint

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Oridonin, a well-known traditional Chinese herbal medicinal product isolated from Isodon rubescens (Hemsl.) H.Hara, has many potential properties, including anti-inflammatory and antioxidant activities. However, there is no evidence whether oridonin have a protective effect on atherosclerosis. This study focused on the effects of oridonin on oxidative stress and inflammation generated from atherosclerosis. The therapeutic effect on atherosclerosis was evaluated by intraperitoneal injection of oridonin in a high-fat fed ApoE−/− mouse model. We isolated mouse peritoneal macrophages and detected the effect of oridonin on oxidized low-density lipoprotein-induced lipid deposition. Oil red O staining, Masson's staining, Dihydroethidium (DHE) fluorescence staining, Immunohistochemical staining, western blotting analysis, immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR were used to evaluate the effect on atherosclerosis and explore the mechanisms. Oridonin treatment significantly alleviated the progression of atherosclerosis, reduced macrophage infiltration and stabilized plaques. Oridonin could significantly inhibit inflammation associated with NLRP3 activation. Oridonin significantly reduced oxidative stress by blocking Nrf2 ubiquitination and degradation. We also found that oridonin could prevent the formation of foam cells by increasing lipid efflux protein and reducing lipid uptake protein in macrophages. Oridonin has a protective effect on atherosclerosis in ApoE−/− mice, which may be related to the inhibition of NLRP3 and the stabilization of Nrf2. Therefore, oridonin may be a potential therapeutic agent for atherosclerosis.

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Section: Discussionsupporting

confidence: 56%

Section: Drug Administrationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oridonin attenuates the progression of atherosclerosis by inhibiting NLRP3 and activating Nrf2 in apolipoprotein E-deficient mice

Wang

Zhao

Ding

et al. 2022

Preprint

Self Cite

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“…As a specific inhibitor of the NLRP3-mediated inflammasome, AER was demonstrated to be effective as a covalent inhibitor capable of reducing upstream inflammatory cytokine triggering. Currently, there is mounting evidence that oridonin can inhibit I/R injury, including injury to the myocardium, lower limbs, brain tissue, and kidney, by downregulating oxidative stress and NLRP3-mediated inflammatory pathways [ 9 , 23 , 24 ]. Although these studies have included metabolomics, exosomes, Mincle, and NF-κB, none of the mechanisms have clarified the key role of GSDMD-mediated pyroptosis [ 25 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Oridonin Protects against Myocardial Ischemia–Reperfusion Injury by Inhibiting GSDMD-Mediated Pyroptosis

Lin

Lai

Fan

et al. 2022

Genes

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Pyroptosis serves a crucial function in various types of ischemia and reperfusion injuries. Oridonin, a tetracycline diterpene derived from Rabdosia rubescens, can significantly inhibit the aggregation of NLRP3-mediated inflammasome. This experiment is aimed at investigating the effect of oridonin on pyroptosis in mice cardiomyocytes. Based on the models of myocardial ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R), Evans Blue/TTC double staining, TUNEL staining, and Western blotting were applied to determine the effects of oridonin on myocardial damage, cellular activity and signaling pathways involved in pyroptosis. During I/R and H/R treatments, the extent of gasdermin D-N domains was upregulated in cardiomyocytes. Apart from that, oridonin improved cell survival in vitro and decreased the myocardial infarct size in vivo by also downregulating the activation of pyroptosis. Finally, the expression levels of ASC, NLRP3 and p-p65 were markedly upregulated in cardiomyocytes after H/R treatment, whereas oridonin suppressed the expression of these proteins. The present experiment revealed that myocardial I/R injury and pyroptosis can be alleviated and inhibited by oridonin pretreatment via NF-κB/NLRP3 signaling pathway, both in vivo and in vitro. Therefore, oridonin may serve as a potentially novel agent for the clinical treatment of myocardial ischemia-reperfusion injuries.

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“…One study shows that SFN has the functions of anti-tumor, anti-oxidation, anti-angiogenesis, and anti-inflammatory agents [ 95 ]. It has been reported that NLRP3-mediated inflammation and oxidative stress mediated by Nrf2 are involved in limb I/R injury [ 96 ]. Moreover, Nrf2 is an important target of SFN in many physiological and pathological processes [ 97 , 98 , 99 ].…”

Section: The Role Of Pyroptosis and Autophagy In Limb Ischemia/reperf...mentioning

confidence: 99%

The Role of Pyroptosis and Autophagy in Ischemia Reperfusion Injury

Zhao

Yang

et al. 2022

Biomolecules

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Pyroptosis is a process of programmed cell death mediated by gasdermin (GSDM) found in recent years. In the process of pyroptosis, caspase-1 or caspase-11/4/5 is activated, which cleaves gasdermin D and separates its N-terminal pore-forming domain (PFD). The oligomers of PFD bind to the cell membrane and form macropores on the membrane, resulting in cell swelling and membrane rupture. Increasing evidence indicates that pyroptosis is involved in many diseases, including ischemia reperfusion injury. Autophagy is a highly conserved catabolic process in eukaryotic cells. It plays an important role in the survival and maintenance of cells by degrading organelles, proteins, and macromolecules in the cytoplasm and recycling degradation products. Increasing evidence shows that dysfunctional autophagy participates in many diseases. Recently, autophagy and pyroptosis have been reported to play a vital role in the process of ischemia/reperfusion injury, but the related mechanisms are not completely clear. Therefore, this article reviews the role of autophagy and pyroptosis in ischemia–reperfusion injury and analyzes the related mechanisms to provide a basis for future research.

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Oridonin attenuates hind limb ischemia–reperfusion injury by modulating Nrf2-mediated oxidative stress and NLRP3-mediated inflammation

Cited by 10 publications

References 41 publications

Oridonin attenuates the progression of atherosclerosis by inhibiting NLRP3 and activating Nrf2 in apolipoprotein E-deficient mice

Oridonin attenuates the progression of atherosclerosis by inhibiting NLRP3 and activating Nrf2 in apolipoprotein E-deficient mice

Oridonin Protects against Myocardial Ischemia–Reperfusion Injury by Inhibiting GSDMD-Mediated Pyroptosis

The Role of Pyroptosis and Autophagy in Ischemia Reperfusion Injury

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