Abstract
Ischemic heart disease has become a major health challenge worldwide. Malva sylvestris L. (MS) is a traditional herbal medicine with anti-inflammatory properties and have been used as antioxidant and anti- inflammatory agent in infectious diseases and inflammatory diseases.In this study, we aimed at elucidating the mechanism of MS against ischemia-reperfusion (I/R)–induced injury in vivo and in vitro. The I/R animal model in rats and oxygen glucose deprivation/re-oxygenation (OGD/Re) model in H9c2 cells were used in this study. MS was used to pre-treat the rats and cells. Electrocardiogram, histology staining, qPCR, ELISA, CCK-8, and circRNA microarray were performed. We found that pre-treatment with MS extract attenuate OGD/Re-induced cell apoptosis and cell viability inhibition in H9c2 cells. In addition, pre-treatment with MS protected against I/R injury in vivo. The protective effects of MS pre-treatment were associated with inflammatory genes expression and cytokines release. Further mechanistic investigation revealed that MS protected cardiomyocytes through regulating circular RNA (circRNA). We identified a novel circRNA circ003593 that mediated the protective role of MS in vitro through NLRP3 complex, which was associated with reperfusion injury salvage kinase (RISK) signaling pathway. Conclusion: this study is the first time to demonstrate the protective role of MS on I/R injury. Our findings reveal a novel circRNA circ003593-mediated the protective role of MS through NLRP3 inflammasome. Circ003593 may serve as a potential therapeutic target for ischemic heart diseases.
Highlights
Ischemic heart disease (IHD) has high mortality and morbidity rates (Lee et al, 2016)
To determine whether Malva sylvestris L. (MS) pre-treatment was able to protect against cardiac injury induced by OGD/Re, we examined the cell viability and cell apoptosis after MS pre-treatment and OGD/Re stimulation
These results suggest that pre-treatment with MS extract attenuates OGD/ Re-induced cell apoptosis and cell viability inhibition in the H9c2 cells, which is associated with cytokines release
Summary
Ischemic heart disease (IHD) has high mortality and morbidity rates (Lee et al, 2016). Many traditional Chinese medicines have been used for treating IHD (Wang D. et al, 2016). (MS) is a traditional herbal medicine that contain essential oils, vitamins C, fatty acids, and various sterols, which have anti-inflammatory properties and have been used as antioxidant and anti- inflammatory agent in infectious diseases and inflammatory diseases (Veshkurova et al, 2006; Hicsonmez et al, 2009; Usami et al, 2013; Martins et al, 2014; Elsagh et al, 2015; Jabri et al, 2017). The mechnisms underlying MS protectes I/R injury are not fully clear. We aimed to elucidate the anti-apoptosis and anti-inflammation mechanism of MS againstischemia-reperfusion (I/R) injury in vivo and in vitro
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