Baicalin ameliorates atherosclerosis by inhibiting NLRP3 inflammasome in apolipoprotein E-deficient mice

Abstract

Background: NLR family pyrin domain containing 3 (NLRP3) inflammasome has been implicated in the development of atherosclerosis and several studies have suggested that inhibiting NLRP3 inflammasome could be a potential therapeutic approach to treat atherosclerosis. Baicalin is a flavone glycoside with anti-inflammation, anti-oxidative activities. The inhibition of NLRP3 inflammasome activation by baicalin has also been described. Therefore, the effects of baicalin on NLRP3 inflammasome activation and atherosclerosis were evaluated in present study. Methods: We established the apolipoprotein E-deficient atherosclerosis mice model. After baicalin treatment, the IL-1, IL-18, and reactive oxygen species (ROS) production, and the plaque area was monitored. We also measured the NLRP3, ASC, caspase-1, ICAM-1, and VCAM-1 expression in atherosclerosis mice after baicalin treatment. We silenced NLRP3 by administration of lentivirus expressing NLRP3 shRNA to atherosclerosis mice and monitored the IL-1, IL-18, and ROS production, and NLRP3 inflammasome activation. Results: Baicalin remarkably inhibited the production of IL-1, IL-18, mitochondria ROS, total ROS, ICAM-1, and VCAM-1. Baicalin reduced the expression of NLRP3 inflammasome and suppressed its activation. Baicalin significantly reduced the plaque area. Silencing NLRP3 resulted in decreased production of IL-1, IL-18, mitochondria ROS, total ROS, ICAM-1, and VCAM-1, and inhibition of NLRP3 inflammasome activation. Conclusion: Baicalin ameliorated atherosclerosis by inhibiting NLRP3 inflammasome.

The Role of NLRP3 Inflammasome in Cerebrovascular Diseases Pathology and Possible Therapeutic Targets

“…NLRP3-Q705K minor allele carriage is associated with an increased risk of stroke/transient ischaemic attack ( Kastbom et al., 2015 ). Inhibition of NLRP3 inflammasome and IL-1β improves neurological deficits, alleviates brain tissue damage ( Ito et al., 2015 ; Wang, Wang, et al., 2015 ; Lammerding et al., 2016 ; Thakkar et al., 2016 ; Hong et al., 2018 ; Ismael et al., 2018 ; Teng et al., 2018 ; Qu et al., 2019 ; Mo et al., 2020 ; Zhang, Zhao, et al., 2020 ), decreases infarct volume, and alleviates the brain oedema post-ischaemic stroke ( Yang et al., 2014 ; Zhang et al., 2014 ; Wang, Li, et al., 2015 ; Lu et al., 2016 ; Qiu et al., 2016 ; He et al., 2017 ; Chen, Xu, et al., 2018 ; Ismael et al., 2018 ; Ma et al., 2019 ).…”

“…Ischaemia/reperfusion or oxygen-glucose deprivation/reoxygenation can induce the first-step signal of NLRP3 activation, resulting in increased proinflammatory cytokines and NLRP3 expression in injured tissues ( Ito et al., 2015 ; Wang, Wang, et al., 2015 ; Chen, Dixon, et al., 2018 ; Lemarchand et al., 2019 ; Zhang, Zhao, et al., 2020 ). Reportedly, the NLRP3 inflammasome was first activated in microglia cells after brain ischaemia/reperfusion injury and then expressed in neurons and microvascular endothelial cells, but mainly in neurons ( Gong et al., 2018 ).…”

“…ROS induced by SAH and intracranial hemorrhage activates NF-κB, thus translocating the p65 subunit into the nucleus and increasing the mRNA levels of NLRP3 and proinflammatory cytokines ( Figure 4 ) ( Shao et al., 2016 ). Activation of the ROS/NF-κB/NLRP3 inflammasome led to early brain injury after SAH and intracranial hemorrhage ( Shao et al., 2016 ), while inhibition of the ROS/NF-κB/NLRP3 inflammasome pathway improved neurological deficits following ischaemia/reperfusion injury (Zhang, Zhao, et al., 2020 ). Zeng et al.…”

“…(2020) and Gong et al. (2018) demonstrated that mitochondrial dysfunction activates the NLRP3 inflammasome in microglia after oxygen-glucose deprivation/reoxygenation ( Gong et al., 2018 ; Zhang, Zhao, et al., 2020 ). The role of ROS and NLRP3 inflammasomes in cerebrovascular diseases may be related to thioredoxin-interacting protein (TXNIP), a widely expressed protein that interacts with thioredoxin.…”

“…In addition, traditional Chinese medicines, such as Baicalin, also have inhibitory effects on the first-step activation of NLRP3 inflammasome. In mouse atherosclerosis models, Baicalin treatment at 50 and 100 mg/kg significantly reduced NLRP3 and caspase-1 mRNA levels and delayed atherosclerosis progression ( Zhao et al., 2020 ).…”