Background: Myocardial ischemia/reperfusion (I/R) injury has become a global public health concern.An increasing amount of evidence has shown that polyphyllin I (PPI) has anti-apoptotic and antioxidant functions. This study was performed to evaluate the cardioprotective effects of PPI in a rat model of myocardial I/R injury and the underlying mechanism.
Methods:We exposed induced a rat model of I/R injury by exposing rat hearts to left anterior descending coronary artery ligation for 30 min, followed by 24 h of reperfusion. Cardiac function was analyzed by echocardiography and HE staining. Myocardial apoptosis, inflammation, and oxidative stress were detected to analyze the PPI's role in I/R injury.
Results:The results showed that pretreatment with PPI improved impaired histological morphology, as shown by histopathological examination. Echocardiography analysis showed that PPI increased the levels of HR, left ventricular ejection fraction (LVEF), and left ventricular wall thickness (LVWT), accompanied by decreased left ventricular end-systolic volume (LVESV). Also, PPI decreased the expression of CK-MB, Mb, cTnI, and LDH. Specifically, PPI also changed the expression of apoptotic makers (Caspase-3, Bax, and Bcl-2), inflammatory cytokines (TNF-α, IL-6, iNOS, and IL-10) and oxidative stress markers (SOD, GSH, ROS, and MDA). Notably, western blot (WB) showed that PPI treatment inhibited the phosphorylation activity of NF-κB p65.
Conclusions:The findings showed that PPI exerted a favorable protective effect on I/R injury by inhibiting the inflammatory response and oxidative stress. It offered new drug candidates for the treatment of myocardial I/R injury.
Background: Andrographolide (Andro) is an active compound extracted from Andrographis, which has protective anti-inflammatory effects. But, its pathological role in coronary heart disease (CHD) is unclear, the aim of this study is to investigate the therapeutic effect of Andro in CHD and explore its potential mechanism.Methods: Here, we established a mouse model of CHD, and rats were randomly divided into 5 groups (n=10): sham, Andro (50 mg/kg), CHD, CHD + Andro (10 mg/kg), and CHD + Andro (50 mg/kg). HE staining was employed to evaluate the pathological changes of myocardial injury cardiac injury. The serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), highdensity lipoprotein cholesterol (HDL-C), nitric oxide (NO), TXA2, ET-1, and prostaglandin I2 (PGI2) were detected by ELISA assay. Myocardial inflammation and the interaction between Andro and PPAR-α/NF-κB axis was measured using western blot.Results: Compared with CHD groups, Andro preserved cardiac injury and decreased the levels of TC, TG, and LDL-C while increasing the level of HDL-C. In addition, Andro also reduced the levels of TNF-α, MCP-1, hs-CRP and IL-1β by shifting the macrophage phenotype and attenuated the endothelial dysfunction by increasing the serum levels of ET-1 and TAX2 and decreasing the levels of NO and PGI2 in mice. Furthermore, Andro impeded cardiac apoptosis and inhibited the activation of PPARα and NF-κB proteins.Conclusions: Andro may represent a medicinal approach for assessing and treating CHD.
Cardiovascular diseases (CVDs) are leading causes of death in the world, owing to noticeable incidence and mortality. traditional Chinese Medicine (tCM) SINI Decoction (SND) is used to prevent and treat CVDs, which has attracted extensive attention for its moderate and little side effects. However, the involved molecular mechanisms are exceedingly complicated and remain unclear. Systems pharmacology, as a novel approach that integrates systems biology and pharmacology plays a significant role in investigating the molecular mechanism of tCM. In systems pharmacology approach, we use to systematically uncover the mechanisms of action in Chinese medicinal formula SND as an effective treatment for CVDs, which mainly includes:1) molecular database building; 2) ADMe evaluation; 3) target-fishing 4) network construction and analysis. The results show that 78 underlying valid ingredients and their corresponding 71 direct targets of SND were obtained. And SND take part in cardiomyocyte protection, blood pressure regulation, and lipid regulation module in treatment of CVDs by cooperative way. Systems pharmacology as an emerging field that investigates the molecular mechanisms of TCM through pharmacokinetic evaluation target prediction, and pathway analysis, which will facilitate the development of traditional Chinese herbs in modern medicine.
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