PPARγ Mediates the Cardioprotective Roles of Danlou Tablet After Acute Myocardial Ischemia-Reperfusion Injury

Abstract

Ischemic heart disease is one of the biggest threats to human life in the world. Reperfusion therapy is an effective strategy to reduce infarct size and ischemic injury. However, reperfusion process may cause secondary myocardial injury which is defined as ischemia-reperfusion injury (IRI). Exploring potential therapeutic strategy to attenuate IRI is extremely important. Danlou tablet (Dan), a Chinese herbal compound consisting of ten herbs, has been identified to be protective for the heart. However, the mechanism of Dan-induced cardioprotection after acute reperfusion was unelucidated. In this study, to investigate the role and mechanism of Dan in myocardial IRI, we performed acute IRI modeling in mice and oxygen-glucose deprivation–reperfusion (OGD/R)-induced apoptosis in primary neonatal rat cardiomyocytes (NRCMs). We found that Dan had protective effect against acute IRI in mice, as evidenced by reduced infarct size, TUNEL-positive cardiomyocytes (CMs), and Bax/Bcl2 ratio and cleaved-caspase 3/caspase 3 ratio in vivo. Meanwhile, Dan inhibited OGD/R-induced apoptosis of NRCMs in vitro. Mechanistically, Dan could activate proliferator-activated receptor gamma (PPARγ) in both IRI hearts and OGD/R-stressed NRCMs, while inhibition of PPARγ attenuated the protective effect of Dan against IRI in vivo and OGD/R-induced CM apoptosis in vitro. These data reveal that Dan attenuates acute myocardial IRI and CM apoptosis through activating PPARγ. Our findings may extend the knowledge of Chinese medicine and provide potential strategy for the precise treatment of ischemic heart diseases.

Danlou tablet inhibits high-glucose-induced cardiomyocyte apoptosis via the miR-34a-SIRT1 axis

“…Thus, proper and effective treatments for DCM are in urgent demand. Dan has been reported to have cardioprotective effects in multiple cardiovascular diseases, such as atherosclerosis, myocardial ischemia-reperfusion injury [ 17 , 19 ], etc. However, whether Dan confers protection against DCM is unclear.…”

“…In addition, Dan protected against myocardial reperfusion injury by regulating endothelial and inducible nitric oxide levels [ 36 ]. Furthermore, a recent study reported that the administration of Dan reduced acute myocardial injury and cardiomyocyte apoptosis by activating PPARγ [ 19 ].…”

“…In the past decades, evidence has shown that Dan confers cardioprotective effects. For example, it is reported that Dan treatment effectively improves arteriosclerosis and reduces myocardial ischemia-reperfusion injury (IRI) [ [17] , [18] , [19] , [20] , [21] , [22] , [23] ]. Moreover, Dan treatment significantly improves cardiac function in patients with myocardial infarction, and the incidence of adverse cardiovascular events is also lower in patients receiving Dan [ 23 ].…”

“…Moreover, Dan treatment significantly improves cardiac function in patients with myocardial infarction, and the incidence of adverse cardiovascular events is also lower in patients receiving Dan [ 23 ]. In addition, a recent study reports that the administration of Dan significantly inhibits cardiomyocyte apoptosis and provides protection against acute IRI [ 19 ]. However, to our knowledge, the effects of Dan on DCM and its therapeutic potential have not been investigated.…”