Polydatin protects against atherosclerosis by activating autophagy and inhibiting pyroptosis mediated by the NLRP3 inflammasome

Zhang, Xiaonan; Wang, Zeping; Li, Xiaoya; Che, Jiye; Yu, Zongliang; Li, Xin; Sun, Changxin; Hu, Lanqing; Wu, Min; Liu, Longtao

doi:10.1016/j.jep.2023.116304

Cited by 17 publications

(9 citation statements)

References 46 publications

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“…However, compared with the LPS group, these events were inhibited by SIM, which indicated that SIM inhibited autophagy‐related proteins and NLRP3‐related proteins expression did not increase in a time‐dependent manner but did fluctuate, thereby decreasing the high levels of autophagy could be a potential strategy for treating and/or preventing inflammation‐related diseases, 52 including inflammatory bone resorption. However, this finding was also inconsistent with some previous literature reports which believed that it was to attenuate the level of inflammation by promoting autophagy, thereby alleviating the development of the inflammation‐related disease 53,54 . Subsequently, the WB results of NLRP3 inhibitor MCC950 clearly showed that SIM inhibited the high expression of autophagy protein in inflammatory state, and there was no significant difference in autophagy level between MCC950 group and SIM + MCC950 group, indicating that SIM and MCC950 had no synergistic effect.…”

Section: Discussioncontrasting

confidence: 71%

“…However, this finding was also inconsistent with some previous literature reports which believed that it was to attenuate the level of inflammation by promoting autophagy, thereby alleviating the development of the inflammation-related disease. 53,54 Subsequently, the WB results of NLRP3 inhibitor MCC950 clearly showed that SIM inhibited the high expression of autophagy protein in inflammatory state, and there was no significant difference in autophagy level between MCC950 group and SIM + MCC950 group, indicating that SIM and MCC950 had no synergistic effect. However, as for treatments with SIM alone failed to suppress the increase of Beclin-1, it may be that compared with MCC950 alone group and SIM + MCC950 group, the inhibitory effect of SIM is not so obvious for this protein.…”

Section: Discussionmentioning

confidence: 99%

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The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway

Cheng,

Jin,

Zheng

et al. 2024

Immunity Inflam & Disease

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BackgroundInflammatory bone resorption is a prominent risk factor for implantation failure. Simvastatin (SIM) has anti‐inflammatory effects independent of cholesterol lowering and reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts. However, the specific mechanism of inflammatory bone loss alleviation by SIM remains to be elucidated. We hypothesized that SIM relieves inflammatory bone loss by modulating autophagy and suppressing the NOD‐like receptor family pyrin domain‐containing protein 3 (NLRP3) signaling pathway.Methods and resultsRAW264.7 cells were stimulated by lipopolysaccharide (LPS) after being pretreated with various concentrations of SIM. Osteoclast (OC) differentiation, formation and activity were evaluated by tartrate‐resistant acid phosphatase staining, F‐actin ring staining and bone resorption pit assays, respectively. We observed autophagosomes by transmission electron microscopy. Then NLRP3 inhibitor MCC950 was used to further explore the corresponding molecular mechanism underlying anti‑inflammatory bone resorption, the expression of autophagy‐related proteins and NLRP3 signaling pathway factors in pre‐OCs were evaluated by western blot analysis, and the expression of OC‑specific molecules was analyzed using reverse transcription‑quantitative polymerase chain reaction. The results showed that SIM decreased the expression of tumor necrosis factor‐α, whereas increased Interleukin‐10. In addition, SIM inhibited LPS‐induced OC differentiation, formation, bone resorption activity, the level of autophagosomes, and OC‑specific markers. Furthermore, SIM significantly suppressed autophagy by downregulating LC3II, Beclin1, ATG7, and NLRP3‐related proteins expression while upregulating P62 under inflammatory conditions.ConclusionsSIM may reduce autophagy secretion to attenuate LPS‐induced osteoclastogenesis and the NLRP3 signaling pathway participates in this process, thus providing theoretical basis for the application of this drug in peri‐implantitis.

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Section: Discussioncontrasting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway

Cheng,

Jin,

Zheng

et al. 2024

Immunity Inflam & Disease

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“…Through CoIP, we found that cFLIP L and Caspase 1 can bind to each other, preventing the proteolytic cleavage of Caspase 1 and inhibiting downstream cascade reactions. In the process of pyroptosis, in addition to being closely related to Caspase 1, it also involves the activation of NLRP3 inflammasome (Zhang et al, 2023). As a multifunctional protein complex, NLRP3 inflammasome can trigger inflammatory cascade reactions, of which NLRP3 is the most widely studied inflammasome, which can respond to the stimulation of various pathogens inside and outside the cell.…”

Section: Discussionmentioning

confidence: 99%

cFLIP_L alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis

Zhang,

Wu,

Liu

et al. 2023

Cell Biology International

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Alleviating myocardial ischemia‐reperfusion injury (MIRI) plays a critical role in the prognosis and improvement of cardiac function following acute myocardial infarction. Pyroptosis is a newly identified form of cell death that has been implicated in the regulation of MIRI. In our study, H9c2 cells and SD rats were transfected using a recombinant adenovirus vector carrying cFLIPL, and the transfection was conducted for 3 days. Subsequently, H9c2 cells were subjected to 4 h of hypoxia followed by 12 h of reoxygenation to simulate an in vitro ischemia‐reperfusion model. SD rats underwent 30 min of ischemia followed by 2 h of reperfusion to establish an MIRI model. Our findings revealed a notable decrease in cFLIPL expression in response to ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R) injuries. Overexpression of cFLIPL can inhibit pyroptosis, reducing myocardial infarction area in vivo, and enhancing H9c2 cell viability in vitro. I/R and H/R injuries induced the upregulation of ASC, cleaved Caspase 1, NLRP3, GSDMD‐N, IL‐1β, and IL‐18 proteins, promoting cell apoptosis. Our research indicates that cFLIPL may suppress pyroptosis by strategically binding with Caspase 1, inhibiting the release of inflammatory cytokines and preventing cell membrane rupture. Therefore, cFLIPL could potentially serve as a promising target for alleviating MIRI by suppressing the pyroptotic pathway.

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“…Crocin, a constituent of saffron, not only exerts anti-atherosclerotic effects by reducing oxidized LDL but also induces M2 macrophage polarization in a rat model of vitamin D3-induced coronary atherosclerosis ( 90 ). Furthermore, polydatin, a bioactive ingredient extracted from the roots of the Reynoutria japonica Houtt, can inhibit multiple signaling pathways including the NF-κB and TLR pathways, reduce the release of pro-inflammatory factors, decrease lipid deposition and foam cell formation, and exert anti-oxidative stress effects, thereby playing a multifaceted anti-atherosclerotic role ( 91 , 92 ). Numerous studies have found that traditional Chinese medicine, both the active monomeric components and mixed compounds, can affect macrophage polarization through various signaling pathways.…”

Section: Macrophage Polarization As a Target For Treating Atheroscler...mentioning

confidence: 99%

Macrophage polarization states in atherosclerosis

Song

et al. 2023

Front. Immunol.

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Atherosclerosis, a chronic inflammatory condition primarily affecting large and medium arteries, is the main cause of cardiovascular diseases. Macrophages are key mediators of inflammatory responses. They are involved in all stages of atherosclerosis development and progression, from plaque formation to transition into vulnerable plaques, and are considered important therapeutic targets. Increasing evidence suggests that the modulation of macrophage polarization can effectively control the progression of atherosclerosis. Herein, we explore the role of macrophage polarization in the progression of atherosclerosis and summarize emerging therapies for the regulation of macrophage polarization. Thus, the aim is to inspire new avenues of research in disease mechanisms and clinical prevention and treatment of atherosclerosis.

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Polydatin protects against atherosclerosis by activating autophagy and inhibiting pyroptosis mediated by the NLRP3 inflammasome

Cited by 17 publications

References 46 publications

The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway

The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway

cFLIP_L alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis

Macrophage polarization states in atherosclerosis

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Polydatin protects against atherosclerosis by activating autophagy and inhibiting pyroptosis mediated by the NLRP3 inflammasome

Cited by 17 publications

References 46 publications

The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway

The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway

cFLIPL alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis

Macrophage polarization states in atherosclerosis

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cFLIP_L alleviates myocardial ischemia‐reperfusion injury by regulating pyroptosis