Oridonin Protects against Myocardial Ischemia–Reperfusion Injury by Inhibiting GSDMD-Mediated Pyroptosis

Abstract

Pyroptosis serves a crucial function in various types of ischemia and reperfusion injuries. Oridonin, a tetracycline diterpene derived from Rabdosia rubescens, can significantly inhibit the aggregation of NLRP3-mediated inflammasome. This experiment is aimed at investigating the effect of oridonin on pyroptosis in mice cardiomyocytes. Based on the models of myocardial ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R), Evans Blue/TTC double staining, TUNEL staining, and Western blotting were applied to determine the effects of oridonin on myocardial damage, cellular activity and signaling pathways involved in pyroptosis. During I/R and H/R treatments, the extent of gasdermin D-N domains was upregulated in cardiomyocytes. Apart from that, oridonin improved cell survival in vitro and decreased the myocardial infarct size in vivo by also downregulating the activation of pyroptosis. Finally, the expression levels of ASC, NLRP3 and p-p65 were markedly upregulated in cardiomyocytes after H/R treatment, whereas oridonin suppressed the expression of these proteins. The present experiment revealed that myocardial I/R injury and pyroptosis can be alleviated and inhibited by oridonin pretreatment via NF-κB/NLRP3 signaling pathway, both in vivo and in vitro. Therefore, oridonin may serve as a potentially novel agent for the clinical treatment of myocardial ischemia-reperfusion injuries.

Effects of “accurate measurement” comprehensive sports activities on balance ability, body composition and bone density of female college students

“…The musculoskeletal benefits of exercise are clearly beneficial for middleaged and older adults (Lim and Goh, 2022;Schaun et al, 2022), and studies have concluded that comprehensive content exercise helps by improving muscle size, muscle strength, balance and physical function in older adults that have decreased because of age (Shahtahmassebi et al, 2022). Due to changing lifestyles and increased academic stress, physical and mental health problems among college students have become increasingly serious, and there are systematic evaluations of qigong exercises considered to improve physical and mental health of college students, with no significant effects on muscle strength found (Lin et al, 2022b). There is also a study of the effects of 8 weeks of resistance training on physical performance and body composition in adolescent athletes, with significant benefits in muscular endurance, strength and static balance (Fayazmilani et al, 2022).…”

Initial Despair and Current Hope of Identifying a Clinically Useful Treatment of Myocardial Reperfusion Injury: Insights Derived from Studies of Platelet P2Y12 Antagonists and Interference with Inflammation and NLRP3 Assembly

“…But inflammasomes are also found in cardiomyocytes themselves [117][118][119][120][121]. Indeed, the hypoxia/reoxygenation of rat cardiomyocytes leads to the release of the N-terminal fragment of GSDMD and cas-1, while their release is significantly curtailed when NLRP3 is inhibited [122]. Furthermore, after NLRP3 inhibition, the expected loss of membrane integrity and the release of LDH as a marker of membrane failure are no longer apparent.…”

Tumor microenvironment‐activatable oridonin‐loaded iron‐based metal–organic frameworks for targeting cancer therapy

“…Oridonin (Ori) is a natural organic compound of kaurene diterpenoids extracted from Isodon rubescens. 1,2 Ori has antitumor, [3][4][5] antibacterial, [6][7][8] antiangiogenesis, 9 delayed aging, 10 and many other biological activities. 11 It can induce apoptosis, 12,13 autophagy, and cell cycle arrest of tumor cells by regulating multiple molecular signal pathways, 14,15 inhibiting the proliferation and metastasis of many cancer cells.…”