Naoxintong attenuates Ischaemia/reperfusion Injury through inhibiting <scp>NLRP</scp>3 inflammasome activation

Wang, Yaqiong; Yan, Xiaoxiang; Mi, Shou-Ling; Li, Zhang; Wang, Yuexiang; Zhu, Hong; Sun, Xiaolei; Zhao, Buchang; Zhao, Chao; Zou, Yunzeng; Hu, Kai; Ding, Xiaoqiang; Sun, Aijun; Ge, Junbo

doi:10.1111/jcmm.12915

Cited by 46 publications

(24 citation statements)

References 35 publications

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“…The expressions of NLRP3, caspase-1, and SIRT1 in heart tissue and H9c2 cells at the protein level were determined by Western blotting analysis as previously described (Wang et al, 2017). Briefly, cardiac tissues and cells were minced and lysed in ice-cold radioimmunoprecipitation assay (RIPA) lysis buffer.…”

Section: Western Blotting Analysismentioning

confidence: 99%

Shikonin Ameliorates LPS-Induced Cardiac Dysfunction by SIRT1-Dependent Inhibition of NLRP3 Inflammasome

et al. 2020

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Shikonin (SHI) is an anti-inflammatory agent extracted from natural herbs. It is still unknown whether SHI ameliorates lipopolysaccharide (LPS)-induced cardiac dysfunction. This study aims to explore the protective effects of SHI on LPS-induced myocardial injury and its mechanism. The LPS-induced cardiac dysfunction mouse model was employed to investigate the protective effects of SHI. In the present study, we found that SHI treatment improved the survival rate and cardiac function and remarkably ameliorated the release of inflammatory cytokines and macrophage infiltration in heart tissue of LPS-treated mice. SHI also reduced lactate dehydrogenase (LDH) and cardiac troponin (cTn) release, cell inflammation, and apoptosis in LPS plus adenosine triphosphate (ATP)-treated H9c2 cells. In addition, SHI significantly upregulated silent information regulator 1 (SIRT1) expression and suppressed the upregulation of NOD-like receptor protein 3 (NLRP3), cleaved caspase-1, and caspase-1 activity in heart tissues induced by LPS. Meanwhile, we got the same results in LPS plus ATP-treated H9c2 cells in vitro. Further, SIRT1 inhibitor or siRNA partially blocked SHI-mediated upregulation of SIRT1 expression and downregulation of NLRP3, cleaved caspase-1, and caspase-1 activity in heart tissues induced by LPS. Therefore, we conclude that SHI ameliorates LPS-induced cardiac dysfunction by inhibiting SIRT1-dependent activation of NLRP3 inflammasomes and might be a promising therapeutic strategy for the treatment of LPS-induced cardiac dysfunction.

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Section: Western Blotting Analysismentioning

confidence: 99%

Shikonin Ameliorates LPS-Induced Cardiac Dysfunction by SIRT1-Dependent Inhibition of NLRP3 Inflammasome

et al. 2020

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“…The NLRP3 inflammasome has previously been proposed as a potential therapeutic target to treat multiple inflammatory diseases [162][163][164][165][166][167][168][169]. Several synthetic [162][163][164][165]167] and natural [166,168] compounds with varying specificity for the NLRP3 pathway have been tested. One promising treatment is MCC950, a specific smallmolecule inhibitor of the NLRP3 inflammasome [95].…”

Section: Principle Findingsmentioning

confidence: 99%

Intra-amniotic inflammation induces preterm birth by activating the NLRP3 inflammasome†

Faro

Romero²,

Schwenkel

et al. 2018

Biology of Reproduction

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Intra-amniotic inflammation is strongly associated with spontaneous preterm labor and birth, the leading cause of perinatal mortality and morbidity worldwide. Previous studies have suggested a role for the NLRP3 (NLR family pyrin domain-containing protein 3) inflammasome in the mechanisms that lead to preterm labor and birth. However, a causal link between the NLRP3 inflammasome and preterm labor/birth induced by intra-amniotic inflammation has not been established. Herein, using an animal model of lipopolysaccharide-induced intra-amniotic inflammation (IAI), we demonstrated that there was priming of the NLRP3 inflammasome (1) at the transcriptional level, indicated by enhanced mRNA expression of inflammasome-related genes (Nlrp3, Casp1, Il1b); and (2) at the protein level, indicated by greater protein concentrations of NLRP3, in both the fetal membranes and decidua basalis prior to preterm birth. Additionally, we showed that there was canonical activation of the NLRP3 inflammasome in the fetal membranes, but not in the decidua basalis, prior to IAI-induced preterm birth as evidenced by increased protein levels of active caspase-1. Protein concentrations of released IL1β were also increased in both the fetal membranes and decidua basalis, as well as in the amniotic fluid, prior to IAI-induced preterm birth. Finally, using the specific NLRP3 inhibitor, MCC950, we showed that in vivo inhibition of the NLRP3 inflammasome reduced IAI-induced preterm birth and neonatal mortality. Collectively, these results provide a causal link between NLRP3 inflammasome activation and spontaneous preterm labor and birth in the context of intra-amniotic inflammation. We also showed that, by targeting the NLRP3 inflammasome, adverse pregnancy and neonatal outcomes can be significantly reduced.

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“…Naoxintong Capsule (NXT) is derived from a classic traditional Chinese prescription named Bu Yang Huan Wu decoction, which is widely used to treat patients with stroke in China. In recent years, more and more clinical studies indicated that NXT can not only ameliorate brain function and promote the recovery of consciousness, but also reduce the plaque area and carotid intima-media thickness [ 9 , 10 ]. However, there is no comprehensive and systematic evidence to confirm its clinical efficacy in patients with CI and carotid atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Naoxintong Capsule in the Treatment of Patients with Cerebral Infarction and Carotid Atherosclerosis: A Systematic Review and Meta‐Analysis of Randomized Trials

Liang

Cai

Chen

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Objective Naoxintong capsule (NXT) has been widely used to treat patients with cerebral infarction and carotid atherosclerosis. However, it is uncertain whether there is robust evidence on the effects of NXT for cerebral infarction and carotid atherosclerosis. A systematic review and meta-analysis of randomized trials were performed to assess the efficacy of NXT in the treatment of cerebral infarction and carotid atherosclerosis. Methods The Cochrane Library, EMBASE, the Medline database, the Wanfang database, the China National Knowledge Infrastructure, and the VIP database were searched up to January 2018 with no language restrictions. Study selection, data extraction, quality assessment, and data analyses were performed according to the Cochrane standards. Results Eleven studies (N=1141) in total satisfied the inclusion criteria for the meta-analysis. The results of meta-analysis showed that compared with the conventional therapy alone, NXT combined with conventional therapy could significantly improve national institutes of health stroke scale (NIHSS) score (MD= -3.92, 95%CI: -4.31~-3.52, P<0.00001), plaque area (MD= -0.16, 95%CI: -0.20~-0.13, P<0.00001), carotid intima-media thickness (IMT) (MD= -0.23, 95%CI: -0.26~-0.20, P<0.00001), total cholesterol (TC) (MD= -0.16, 95%CI: -0.79~-0.42, P<0.00001), triglyceride (TG) (MD= -0.69, 95%CI: -0.88~-0.51, P<0.00001), high-density lipoprotein cholesterol (HDL-C) (MD= 0.23, 95%CI: 0.15~0.31, P<0.00001), and low-density lipoprotein cholesterol (LDL-C) (MD= -0.42, 95%CI: -0.58~-0.25, P<0.00001). There were no reported adverse events in the studies. Conclusions NXT is an effective and safe therapy option for patients with cerebral infarction and carotid atherosclerosis. However, due to the high clinical heterogeneity and small sample size of the included trials, further standardized preparation, large-scale and rigorously designed trials are needed.

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Naoxintong attenuates Ischaemia/reperfusion Injury through inhibiting NLRP3 inflammasome activation

Cited by 46 publications

References 35 publications

Shikonin Ameliorates LPS-Induced Cardiac Dysfunction by SIRT1-Dependent Inhibition of NLRP3 Inflammasome

Shikonin Ameliorates LPS-Induced Cardiac Dysfunction by SIRT1-Dependent Inhibition of NLRP3 Inflammasome

Intra-amniotic inflammation induces preterm birth by activating the NLRP3 inflammasome†

The Effect of Naoxintong Capsule in the Treatment of Patients with Cerebral Infarction and Carotid Atherosclerosis: A Systematic Review and Meta‐Analysis of Randomized Trials

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