Myricitrin attenuates memory impairment in a rat model of sepsis-associated encephalopathy via the NLRP3/Bax/Bcl pathway

Abstract

Introduction: The present investigation determined the protective effect of myricitrin against sepsis-associated encephalopathy in rats. Material and methods: Sepsis was induced by cecal ligation and puncture (CLP); rats were treated with 30 or 100 mg/kg of myricitrin for 5 days prior to the induction of CLP. The effect of myricitrin was observed by determining the neurological function using the open field test and step-down inhibitory avoidance test. Cerebral oedema and the levels of inflammatory and oxidative stress mediators were determined in brain tissues. Moreover, the expression levels of Bcl-2, Bax, IκB-α, nuclear factor κB (NF-κB), caspase-3 and NLRP3 were estimated in brain tissues by Western blotting and the mRNA expression of NF-κB, caspase-3 and NLRP3 in brain tissues was estimated by realtime polymerase chain reaction. An immunofluorescence assay was performed to estimate inflammasome activity. Results: The results suggest that treatment with myricitrin protects neuronal function in rats with CLP-induced sepsis. Decreases in inflammation and oxidative stress mediators were observed in the brain tissues of the myricitrin-treated group compared to the CLP group. Moreover, treatment with myricitrin ameliorated the altered Bcl-2, Bax, IκB-α, NF-κB, caspase-3 and NLRP3 protein and mRNA expression levels in the brain tissues of septic rats. Conclusions: The data reveal that myricitrin ameliorated neuroinflammation and improved memory in rats with CLP-induced sepsis by regulating the NLRP3/Bax/Bcl signalling pathway.

Malvidin alleviates mitochondrial dysfunction and ROS accumulation through activating AMPK-α/UCP2 axis, thereby resisting inflammation and apoptosis in SAE mice

“…Several studies have demonstrated that flavonoids alleviate sepsis brain injury (Zhu et al, 2019), memory impairment (Gong et al, 2019), cognitive dysfunction (Karimian, 2020) by exerting their antioxidant and anti-inflammatory functions.…”

“…The aim of this study is to investigate the pathogenesis of SAE and look for effective prophylactic drugs aiming to provide early clinical intervention for SAE patients to treat brain dysfunction, thereby reducing sepsis mortality and improving the quality of life of SAE patients. Several studies have demonstrated that flavonoids alleviate sepsis brain injury ( Zhu et al, 2019 ), memory impairment ( Gong et al, 2019 ), cognitive dysfunction ( Karimian, 2020 ) by exerting their antioxidant and anti-inflammatory functions. As a member of the flavonoids family, malvidin alleviates inflammation and oxidative stress in several LPS-mediated injury models ( Bastin et al, 2020 ).…”

“…Flavonoids are the most common active polyphenols, widely distributed in plants, with a variety of pharmacological effects, including anti-inflammatory ( Hussain et al, 2016 ), anti-cancer ( Kopustinskiene et al, 2020 ), anti-proliferative ( Fernández et al, 2021 ), antioxidant, and inhibition of free radical-mediated processes ( Parhiz et al, 2015 ). Many studies have reported that flavonoids alleviate sepsis-induced brain injury ( Zhu et al, 2019 ), memory impairment ( Gong et al, 2019 ), cognitive dysfunction ( Karimian, 2020 ), and sepsis-induced lung damage ( Toklu et al, 2008 ), kidney damage ( Ren et al, 2020 ), and heart damage ( Wu B. et al, 2020 ) through antioxidant and anti-inflammatory functions. Anthocyanins are a group of flavonoids with similar anti-inflammatory and antioxidant properties to other members of flavonoids family ( Aqil et al, 2012 ).…”

The Neuroprotective Effect of Short Chain Fatty Acids Against Sepsis-Associated Encephalopathy in Mice

“…In gram-negative sepsis, LPS induced activation of NF-κB, which translocated to the nucleus where it promotes transcription of inflammatory mediators, including COX-2 ( 89 ). In the brain tissues of the CLP-induced mice, the expression of NF-κB was enhanced ( 90 ). The study showed that exogenous SCFAs, especially butyrate, can block the activation of NF-B in diabetic glomerulonephritis mice ( 91 ) and Usami, M. et al.…”

Myricetin attenuates hypoxic-ischemic brain damage in neonatal rats via NRF2 signaling pathway

“…It has been reported that myricetin could alleviate intestinal ischemia-reperfusion induced injury through attenuating inflammatory responses and oxidative stress ( Sun Y et al, 2018 ). In addition, myricetin could exert a protective effect on sepsis-associated encephalopathy through modulating inflammasome and apoptotic signaling ( Gong et al, 2019 ). However, there is a lack of research on myricetin in HIE.…”