Cardioprotective Effects of Puerarin-V on Isoproterenol-Induced Myocardial Infarction Mice Is Associated with Regulation of PPAR-Υ/NF-κB Pathway.

Abstract

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.

• Authors: Xuguang Li, Tianyi Yuan, Di Chen, Yucai Chen, Shuchan Sun, Danshu Wang, Lianhua Fang, Yang Lu, Guanhua Du
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 23 Issue 12 (Dec 14 2018) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 30558188 (Publication Type: Journal Article)

Chemical References

• Interleukin-1beta
• Interleukin-6
• Isoflavones
• NF-kappa B
• Peroxisome Proliferator-Activated Receptors
• Tumor Necrosis Factor-alpha
• Isoproterenol
• puerarin

Topics

• Animals
• Coronary Vessels (cytology)
• Electrocardiography
• Endothelial Cells (drug effects)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Isoflavones (therapeutic use)
• Isoproterenol (toxicity)
• Male
• Mice
• Mice, Inbred C57BL
• Myocardial Infarction (chemically induced)
• NF-kappa B (metabolism)
• Peroxisome Proliferator-Activated Receptors (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)