Puerarin is a well-known traditional Chinese medicine which has been used for the treatment of cardiovascular diseases. Recently, a new advantageous crystal form of puerarin, puerarin-V, has been developed. However, the cardioprotective effects of puerarin-V on myocardial infarction (MI) heart failure are still unclear. In this research, we aim to evaluate the cardioprotective effects of puerarin-V on the isoproterenol (ISO)-induced MI mice and elucidate the underlying mechanisms. To induce MI in C57BL/6 mice, ISO was administered at 40 mg/kg subcutaneously every 12 h for three times in total. The mice were randomly divided into nine groups: (1) control; (2) ISO; (3) ISO + puerarin injection; (4–9) ISO + puerarin-V at different doses and timings. After treatment, cardiac function was evaluated by electrocardiogram (ECG), biochemical and histochemical analysis. In vitro inflammatory responses and apoptosis were evaluated in human coronary artery endothelial cells (HCAECs) challenged by lipopolysaccharide (LPS). LPS-induced PPAR-Υ/NF-κB and subsequently activation of cytokines were assessed by the western blot and real-time polymerase chain reaction (PCR). Administration of puerarin-V significantly inhibits the typical ST segment depression compared with that in MI mice. Further, puerarin-V treatment significantly improves ventricular wall infarction, decreases the incidence of mortality, and inhibits the levels of myocardial injury markers. Moreover, puerarin-V treatment reduces the inflammatory milieu in the heart of MI mice, thereby blocking the upregulation of proinflammatory cytokines (TNF-α, IL-1β and IL-6). The beneficial effects of puerarin-V might be associated with the normalization in gene expression of PPAR-Υ and PPAR-Υ/NF-κB /ΙκB-α/ΙΚΚα/β phosphorylation. In the in vitro experiment, treatment with puerarin-V (0.3, 1 and 3 μM) significantly reduces cell death and suppresses the inflammation cytokines expression. Likewise, puerarin-V exhibits similar mechanisms. The cardioprotective effects of puerarin-V treatment on MI mice in the pre + post-ISO group seem to be more prominent compared to those in the post-ISO group. Puerarin-V exerts cardioprotective effects against ISO-induced MI in mice, which may be related to the activation of PPAR-γ and the inhibition of NF-κB signaling in vivo and in vitro. Taken together, our research provides a new therapeutic option for the treatment of MI in clinic.

The endothelial-to-mesenchymal transition (EndMT) has been demonstrated to be involved in pulmonary vascular remodeling. It is partly attributed to oxidative and inflammatory stresses in endothelial cells. In current study, we conducted a series of experiments to clarify the effect of salvianolic acid A (SAA), a kind of polyphenol compound, in the process of EndMT in human pulmonary arterial endothelial cells and in vivo therapeutic efficacy on vascular remodeling in monocrotaline (MCT)-induced EndMT. EndMT was induced by TGFβ1 in human pulmonary arterial endothelial cells (HPAECs). SAA significantly attenuated EndMT, simultaneously inhibited cell migration and reactive oxygen species (ROS) formation. In MCT-induced pulmonary arterial hypertension (PAH) model, SAA improved vascular function, decreased TGFβ1 level and inhibited inflammation. Mechanistically, SAA stimulated Nrf2 translocation and subsequent heme oxygenase-1 (HO-1) up-regulation. The effect of SAA on EndMT in vitro was abolished by ZnPP, a HO-1 inhibitor. In conclusion, this study indicates a deleterious impact of oxidative stress on EndMT. Polyphenol antioxidant treatment may provide an adjunctive action to alleviate pulmonary vascular remodeling via inhibiting EndMT.

Heart failure with preserved ejection fraction (HFpEF) is a morbid, fatal, and common syndrome for which lack of evidence-based therapies. Salvianolic acid A (SAA), a major active ingredient of Salvia miltiorrhiza Burge, has shown potential to protect against cardiovascular diseases. This study aims to elucidate whether SAA possessed therapeutic activity against HFpEF and explore the potential mechanism. HFpEF mouse model was established infusing a combination of high-fat diet (HFD) and Nω-nitro-L-arginine methyl ester (L-NAME) for 14 weeks. After 10 weeks of feeding, HFpEF mice were given SAA (2.5, 5, 10 mg/kg) via oral gavage for four weeks. Body weight, blood pressure, blood lipids, glucose tolerance, exercise performance, cardiac systolic/diastolic function, cardiac pathophysiological changes, and inflammatory factors were assessed. Experimental results showed that SAA reduced HFpEF risk factors, such as body weight gain, glucose intolerance, lipid disorders, and increased exercise tolerance in HFpEF mice. Moreover, SAA not only relieved myocardial hypertrophy and fibrosis by reducing interventricular septal wall thickness, left ventricular posterior wall thickness, left ventricular mass, heart index, cardiomyocyte cross-sectional area and cardiac collagen content, but also improved cardiac diastolic function via reducing E/E' ratio. Finally, SAA inhibited TLR2/TLR4-mediated Myd88 activation and its downstream molecules TRAF6 and IRAK4, which decreases the release of proinflammatory cytokines and mediators through NF-κB and p38 MAPK pathways. In conclusion, SAA could attenuate cardiac inflammation and cardiac disfunction by TLR/Myd88/TRAF/NF-κB and p38MAPK/CREB signaling pathways in HFpEF mice, which provides evidence for SAA as a potential drug for treatment of HFpEF in clinic.