Oridonin Attenuates Myocardial Ischemia/Reperfusion Injury via Downregulating Oxidative Stress and NLRP3 Inflammasome Pathway in Mice

Abstract

Oridonin (ORI), the major pharmacological component extracted from a traditional Chinese medicine, possesses a beneficial effect on myocardial ischemia/reperfusion (I/R) injury. However, the underlying molecular mechanism by which ORI effects take place is not completely known. Thus, whether ORI works via downregulating oxidative stress and nod-like receptor protein-3 (NLRP3) inflammasome pathway was investigated in this study. Mice underwent surgery to induce myocardial I/R injury, and some were administered ORI (10 mg/kg/day) pretreatment, while others were not. The myocardial enzymes’ levels, infarct area, and inflammatory injury were measured. The activation situation of oxidative stress and NLRP3 inflammasome was also detected. We found that ORI pretreatment significantly alleviated CK-MB and cTnI levels and infarct size induced by I/R. ORI mitigated the inflammatory injury by decreasing the pathological damage and lowering TNF-α, IL-1β, and IL-18 levels. Moreover, the SOD1 and eNOS levels were significantly increased by ORI, while MDA and iNOS levels were relatively decreased. The oxidative stress was reversed using ORI pretreatment. Importantly, NLRP3 inflammasome pathway was also inhibited by ORI, as reflected by the lower protein levels of NLRP3, caspase-1, and IL-1β. In conclusion, ORI alleviates myocardial injury induced by I/R via inhibiting the oxidative stress and NLRP3 inflammasome pathway.

Oridonin ameliorates depressive-like behaviors induced by chronic unpredictable mild stress in mice via TXNIP/NLRP3 signaling pathway

“…Oridonin inhibited the expression of TXNIP, NLRP3, and cleaved caspase-1 induced by CUMS, suggesting a possible mechanism for the anti-depression effects of oridonin. A similar effect of oridonin was found in mice with myocardial ischemia/reperfusion (I/R) injury [10]. Oridonin alleviated I/R induced myocardial injury by inhibiting oxidative stress and the NLRP3 inflammasome pathway [10].…”

“…A similar effect of oridonin was found in mice with myocardial ischemia/reperfusion (I/R) injury [10]. Oridonin alleviated I/R induced myocardial injury by inhibiting oxidative stress and the NLRP3 inflammasome pathway [10].…”

“…It has attracted increased attention because of its various pharmacological effects, including antiinflammatory and anti-oxidant activities [9]. For example, oridonin binds NLRP3, a central component of the inflammasome, and further inhibits NLRP3 inflammasome activation [10]. In vitro, oridonin inhibits the expression of inducible nitric oxide synthase and prostaglandinendoperoxide synthase 2 by inhibiting nuclear factor kappa B DNA binding activity [11].…”

Oridonin: A Review of Its Pharmacology, Pharmacokinetics and Toxicity

“…As reported by researches in recent years, oridonin exhibited beneficial influences on cardiovascular disease. In a myocardial ischemia-reperfusion injury mouse models, down-regulation of oxidative stress and NLRP3 inflammation has been shown to mitigative effect of oridonin to myocardial ischemia reperfusion injury ( Lu et al, 2020 ). Similar results have been verified by researchers from the perspective of metabonomics ( Zhang J. et al, 2019 ).…”

Interplays between inflammasomes and viruses, bacteria (pathogenic and probiotic), yeasts and parasites

“…Several data are showed that in an NLRP3 inflammasome-dependent manner oridonin exerts therapeutic effects on myocardial ischemia, liver fibrosis, neuroinflammation, colitis and sepsis. Also, there are reports that oridonin reduces lung inflammation and improves survival in SARS-CoV-infected animals [ [127] , [128] , [129] , [130] , [131] ]. The mechanism of oridonin action is based on the suppression of NF-κB or MAPK activity and inhibition of inflammasome-independent pro-inflammatory cytokines releases, such as TNF-α and IL-6 [ 132 ].…”