Panax quinquefolius L. Saponins Protect Myocardial Ischemia Reperfusion No-Reflow Through Inhibiting the Activation of NLRP3 Inflammasome via TLR4/MyD88/NF-κB Signaling Pathway

Abstract

At present, many patients who undergo reperfusion immediately after percutaneous coronary intervention will undergo microvascular obstruction and reduction in myocardial blood flow. This phenomenon is called “no-reflow (NR),” and there is still no effective therapy for NR. Studies showed Panax quinquefolius L. saponins (PQS) have effect on MI/R injury, while the effect and mechanism of PQS on MI/R induced NR are not clear. In this study, we established a MI/R model to investigate whether PQS decrease NR phenomenon via suppression of inflammation. We found that PQS significantly alleviated the symptoms of NR by reducing ischemia, infarction, and NR area; improving cardiac function; preventing pathological morphology changes of myocardium; depressing leukocytes’ aggregation and adhesion; and suppressing the excessive inflammation. Further study demonstrated that PQS remarkably inhibited TLR4, MyD88, p-NF-κB, and NLRP3 inflammasome-associated protein, and these effects could be reversed by LPS. These results indicated that PQS may protect NR by inhibiting the activation of NLRP3 inflammasome via TLR4/MyD88/NF-κB signaling pathway in part, suggesting that PQS exist potential in preventing NR induced by MI/R.

LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes

“…Furthermore, octreotide and melatonin reduce inflammasome-induced pyroptosis through suppressing TLR4-NF-κB-NLRP3 pathway in hepatic I/R damage ( 33 ). In this study, TLR4/MyD88/NF-κB/NLRP3 inflammasome pathway was activated in myocardial I/R tissues, consistent with a previous study ( 34 ). Silencing PVT1 decreased the activation of TLR4/MyD88/NF-κB/NLRP3 pathway.…”

Inhibition of Lipopolysaccharide-Induced Inflammatory and Oxidative Responses by Trans-cinnamaldehyde in C2C12 Myoblasts

“…TLR4/Myd88/NF-κB is known as a classical signaling pathway whose activation is consider to be responsible for the massive inflammation and considered to be a valuable and promising therapeutic target against inflammation related diseases 57 - 60 . Yu et al 58 reported that Panax quinquefolius L . Saponins protect myocardial ischemia reperfusion through blocking TLR4/Myd88/NF-κB signaling pathway suggesting it can be potential therapeutic target pathway for preventing myocardial ischemia.…”

Geniposide suppresses NLRP3 inflammasome-mediated pyroptosis via the AMPK signaling pathway to mitigate myocardial ischemia/reperfusion injury

“…The activation of inflammasome can further induce pyroptosis. Pyroptosis is a type of inflammatory programmed cell death closely correlated with NLRP3 inflammasome including NLRP3, ASC, caspase-1, and N-GSDMD proteins [8]. The activation of NLRP3 inflammasome and gasdermin D (GSDMD), instead of apoptotic caspase, is essential for inducing cell pyroptosis which is manifested as DNA damage, cell swelling, formation of cell membrane pores and release of cellular contents.…”

“…Fig 8. The underlying molecular mechanisms of the protective effects of geniposide against the myocardial ischemia/reperfusion injury of mice.…”