NLRP3 Inflammasome in Atherosclerosis: Putting Out the Fire of Inflammation

Shao, Bo-Zong; Xu, Huibi; Zhao, Yicheng; Zheng, Xiaorui; Wang, Fang; Zhao, Guan-Ren

doi:10.1007/s10753-022-01725-x

Cited by 14 publications

(13 citation statements)

References 138 publications

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“…The CANTOS showed that canakinumab increased the risk of sepsis and deadly infections (Ridker et al, 2017). Pharmacological suppression of NLRP3 in ammasome activation may provide a more targeted and advantageous treatment strategy for CVDs (Grebe et al, 2018;Satish and Agrawal, 2020;Shao et al, 2022). In Comparison to canakinumab, which all block IL-1β function, the risk of fatal infections is predicted to be decreased due to speci c NLRP3 in ammasome inhibition (Soehnlein and Libby, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…In Comparison to canakinumab, which all block IL-1β function, the risk of fatal infections is predicted to be decreased due to speci c NLRP3 in ammasome inhibition (Soehnlein and Libby, 2021). Multiple studies have demonstrated that inhibition of NLRP3 activation has a protective effect on atherosclerosis (Hu et al, 2018;Shao et al, 2022;Zhao et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Once stimulated, caspase-1 is activated by the NLRP3 in ammasome, resulting in the maturation of pro-IL-1β from an inactive state. Increasing evidence suggests that the NLRP3 in ammasome plays an essential role in atherosclerotic development (Shao et al, 2022). Previous studies have revealed that the activation of NLRP3 in ammasome contributes to the vascular in ammatory response, which leads to cholesterol accumulation by impairing cellular cholesterol e ux (Tall and Yvan-Charvet, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…NLRP3 is activated by a variety of endogenous danger signals, such as oxidized low-density lipoprotein (ox-LDL) and cholesterol crystals, which are abundant in macrophages of atherosclerotic lesions. (Liu et al, 2014;Shao et al, 2022). Once stimulated, caspase-1 is activated by the NLRP3 in ammasome, resulting in the maturation of pro-IL-1β from an inactive state.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Wang

Zhao

Ding

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…NLRP3 inflammasome agonists are diverse, such as adenosine triphosphate (ATP), bacterial toxins, and microcrystalline substances. 11 More and more studies have confirmed that different NLRP3 agonists can cause mitochondrial damage, resulting in the release of fragmented mitochondrial DNA (mtDNA) and mitochondrial reactive oxygen species (mtROS). 12 Therefore, alleviating mitochondrial damage prevents activation of NLRP3 inflammasome.…”

Section: Introductionmentioning

confidence: 99%

Ononin alleviates DSS‐induced colitis through inhibiting NLRP3 inflammasome via triggering mitophagy

Liang

et al. 2023

Immunity Inflam & Disease

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Background: Ononin, a flavonoid isolated from Astragalus membranaceus root, is the active ingredient of A. membranaceus and has potential anti‐inflammatory properties, but its effect on colitis is unclear. Aims: This study aimed to explore the anticolitis effect of Ononin by establishing a colitis model in mice induced by dextran sulfate sodium (DSS). Methods: Male C57BL/6 mice were provided DSS, then treated with Ononin (10, 20, 40 mg/kg) or 5‐ASA (40 mg/kg). The colitis symptoms were observed, the disease activity index (DAI) score were recorded daily, and colonic inflammation was evaluted by histopathological scoring. The expression of cytokines, inflammatory mediators, and mitophagy/NLRP3 inflammasome‐related proteins were measured. Results: Ononin significantly alleviated weight loss and colon shortening in mice with colitis ( p < .01). Moreover, Ononin decreased the production of inflammatory cytokines and mediators associated with colitis ( p < .05). In addition, Ononin inhibited macrophages infiltration and reduced caspase‐1 activation in colitis mice. Caspase‐1 activation is closely related to the NLRP3 inflammasome. Therefore, we investigated the effect of Ononin on NLRP3 inflammasome in vitro. The relevant results confirmed that Ononin inhibited NLRP3 inflammasome activation and inhibited mitochondrial damage ( p < .05). Further studies revealed that Ononin inhibited mitochondrial damage through triggering mitophagy ( p < .05). Conclusion: Ononin alleviates DSS‐induced colitis by activating mitophagy to inhibit NLRP3 inflammasome.

show abstract

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

et al. 2023

View full text Add to dashboard Cite

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 fluorescence staining, immunohistochemical staining, western blotting analysis, immunofluorescence, enzyme-linked immunosorbent assay 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.

show abstract

NLRP3 Inflammasome in Atherosclerosis: Putting Out the Fire of Inflammation

Cited by 14 publications

References 138 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

Ononin alleviates DSS‐induced colitis through inhibiting NLRP3 inflammasome via triggering mitophagy

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

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