Cardioprotective activity of ethyl acetate extract of Cinnamomi Ramulus against myocardial ischemia/reperfusion injury in rats via inhibiting NLRP3 inflammasome activation and pyroptosis

Peng, Li‐Xia; Lei, Ziqin; Rao, Zhili; Yang, Ruocong; Zheng, Lang; Fan, Yuxin; Luan, Fei; Zeng, Nan

doi:10.1016/j.phymed.2021.153798

Cited by 35 publications

(21 citation statements)

References 44 publications

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“…TLR4/NF-κB is a classic LPS-induced inflammatory signaling pathway. After microbial infection, NLRP3 inflammasome is activated through TLR4/NF-κB pathway with an increased expression level, acting as an important molecule in cell pyroptosis [ 27 , 28 ]. α-Klotho protein has a therapeutic activity in contrast-induced AKI by limiting NLRP3 inflammasome-mediated pyroptosis [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Knocking down ETS Proto-oncogene 1 (ETS1) alleviates the pyroptosis of renal tubular epithelial cells in patients with acute kidney injury by regulating the NLR family pyrin domain containing 3 (NLRP3) transcription

et al. 2022

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Acute kidney injury (AKI) has a high mortality rate, but its pathogenesis remains unclear Lipopolysaccharide (LPS)-mediated renal tubular epithelial pyroptosis is involved in the pathogenesis of AKI. NLR family of pyrin domains containing 3 (NLRP3) plays an important role in pyroptosis. To further understand the transcriptional regulation mechanism of NLRP3, the peripheral blood of patients with AKI was analyzed in this study, showing that the levels of NLRP3 and cell pyroptosis in patients with AKI were significantly higher than those in normal controls. Furthermore, elevated levels of NLRP3 and cell pyroptosis were found in renal tubular epithelial cells after LPS treatment. Transcription factor ETS Proto-Oncogene 1 (ETS1) could bind to the upstream promoter transcription site of NLRP3 to transactivate NLRP3 in renal tubular epithelial cells. The cell pyroptosis level also decreased by knocking down ETS1. It is concluded that knocking down of ETS1 may reduce the renal tubular epithelial pyroptosis by regulating the transcription of NLRP3, thus relieving AKI. ETS1 is expected to be a molecular target for the treatment of AKI.

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Section: Discussionmentioning

confidence: 99%

Knocking down ETS Proto-oncogene 1 (ETS1) alleviates the pyroptosis of renal tubular epithelial cells in patients with acute kidney injury by regulating the NLR family pyrin domain containing 3 (NLRP3) transcription

et al. 2022

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“…Nevertheless, it also causes further myocardial damage ( Virani et al, 2020 ; Ren et al, 2021 ). MIRI is characterized by metabolic disturbance, cardiac dysfunction, inflammatory reaction, and cell death (apoptosis, autophagy, necrocytosis, pyroptosis, ferroptosis) ( Moens et al, 2005 ; Eltzschig and Eckle, 2011 ; Hwang et al, 2021 ; Lv et al, 2021 ; Peng et al, 2021 ).…”

Section: Myocardial Cell Apoptosis In Myocardial Ischemia/reperfusion...mentioning

confidence: 99%

Inhibition of Myocardial Cell Apoptosis Is Important Mechanism for Ginsenoside in the Limitation of Myocardial Ischemia/Reperfusion Injury

Chen

et al. 2022

Front. Pharmacol.

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Ischemic heart disease has a high mortality, and the recommended therapy is reperfusion. Nevertheless, the restoration of blood flow to ischemic tissue leads to further damage, namely, myocardial ischemia/reperfusion injury (MIRI). Apoptosis is an essential pathogenic factor in MIRI, and ginsenosides are effective in inhibiting apoptosis and alleviating MIRI. Here, we reviewed published studies on the anti-apoptotic effects of ginsenosides and their mechanisms of action in improving MIRI. Each ginsenoside can regulate multiple pathways to protect the myocardium. Overall, the involved apoptotic pathways include the death receptor signaling pathway, mitochondria signaling pathway, PI3K/Akt signaling pathway, NF-κB signaling pathway, and MAPK signaling pathway. Ginsenosides, with diverse chemical structures, regulate different apoptotic pathways to relieve MIRI. Summarizing the effects and mechanisms of ginsenosides contributes to further mechanism research studies and structure–function relationship research studies, which can help the development of new drugs. Therefore, we expect that this review will highlight the importance of ginsenosides in improving MIRI via anti-apoptosis and provide references and suggestions for further research in this field.

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“…The nucleotide-binding domain, leucine-rich repeat containing receptor (NLR) proteins, which consist of pyrin domain-containing (NLRP) proteins NLRP1 and NLRP3 and CARD-containing (NLRC) receptor NLRC4, belong to the intracellular pathogen family and danger signal sensors and are part of the innate immunity effector molecules [6]. They can recruit the effector procaspase-1 and CARD, the apoptosis-associated speck-like protein, to form a series of multimeric protein complexes [7]. The activation of inflammasome can further induce pyroptosis.…”

Section: Introductionmentioning

confidence: 99%

Geniposide suppresses NLRP3 inflammasome-mediated pyroptosis via the AMPK signaling pathway to mitigate myocardial ischemia/reperfusion injury

Yang

Zhang

et al. 2022

Chin Med

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Background NLRP3 inflammasome activation and pyroptosis play a significant role in myocardial ischemia reperfusion injury (MI/RI). Geniposide was reported to show potential therapeutic use for MI/RI with its anti-inflammatory and anti-oxidative properties. However, research on the specific mechanism of geniposide has not been reported. Methods The MIRI model of animal was created in male C57BL/6J mice and the hypoxia reoxygenation (H/R) model was established for the in vitro experiments. Neonatal rat ventricular myocytes (NRVMs) and H9c2 cells with knockdown of TXNIP or NLRP3 were used. Geniposide was administered to mice before vascular ligation. HE staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, echocardiography, oxidative stress and myocardial enzyme detection were used to evaluate the cardioprotective effect of geniposide. Meanwhile, pharmacological approaches of agonist and inhibitor were used to observe potential pathway for geniposide cardioprotective in vitro and in vivo. Moreover, ELISA kits were adopted to detect the levels of inflammatory factors, such as IL-1β and IL-18. The gene and protein expression of NLRP3 and pyroptosis-related factors in heart tissue were performed by RT-PCR, western blotting and immunofluorescence in vivo and in vitro, respectively. Results Our results indicate that geniposide can reduce the area of myocardial infarction, improve heart function, and inhibit the inflammatory response in mice after MI/RI. In addition, RT-PCR and western blotting shown geniposide promoting AMPK phosphorylation to activate myocardium energy metabolism and reducing the levels of genes and proteins expression of NLRP3, ASC, N-GSDMD and cleaved caspase-1, IL-1β, IL-18. Meanwhile, geniposide improved NRVMs energy metabolism, which decreased ROS levels and the protein expression of TXNIP and thus suppressed the expression of NLRP3. AMPK antagonist or agonist and siRNA downregulation of TXNIP or NLRP3 were also verify the effect of geniposide against H/R injury. Further research found that geniposide promoted the translocation of TXNIP and reduce the binding of TXNIP and NLRP3. Conclusions In our study, geniposide can significantly inhibit NLRP3 inflammasome activation via the AMPK signaling pathway and inhibit pyroptosis of cardiomyocytes in myocardial tissues.

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Cardioprotective activity of ethyl acetate extract of Cinnamomi Ramulus against myocardial ischemia/reperfusion injury in rats via inhibiting NLRP3 inflammasome activation and pyroptosis

Cited by 35 publications

References 44 publications

Knocking down ETS Proto-oncogene 1 (ETS1) alleviates the pyroptosis of renal tubular epithelial cells in patients with acute kidney injury by regulating the NLR family pyrin domain containing 3 (NLRP3) transcription

Knocking down ETS Proto-oncogene 1 (ETS1) alleviates the pyroptosis of renal tubular epithelial cells in patients with acute kidney injury by regulating the NLR family pyrin domain containing 3 (NLRP3) transcription

Inhibition of Myocardial Cell Apoptosis Is Important Mechanism for Ginsenoside in the Limitation of Myocardial Ischemia/Reperfusion Injury

Geniposide suppresses NLRP3 inflammasome-mediated pyroptosis via the AMPK signaling pathway to mitigate myocardial ischemia/reperfusion injury

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