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Cardioprotective Effects of Puerarin-V on Isoproterenol-Induced Myocardial Infarction Mice Is Associated with Regulation of PPAR-Υ/NF-κB Pathway
- Source :
- Molecules, Volume 23, Issue 12, Molecules, Vol 23, Iss 12, p 3322 (2018)
- Publication Year :
- 2018
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2018.
-
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<br />(2) ISO<br />(3) ISO + puerarin injection<br />(4&ndash<br />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-&Upsilon<br />/NF-&kappa<br />B 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-&alpha<br />IL-1&beta<br />and IL-6). The beneficial effects of puerarin-V might be associated with the normalization in gene expression of PPAR-&Upsilon<br />and PPAR-&Upsilon<br />B /&Iota<br />&kappa<br />B-&alpha<br />/&Iota<br />&Kappa<br />&alpha<br />/&beta<br />phosphorylation. In the in vitro experiment, treatment with puerarin-V (0.3, 1 and 3 &mu<br />M) 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-&gamma<br />and the inhibition of NF-&kappa<br />B signaling in vivo and in vitro. Taken together, our research provides a new therapeutic option for the treatment of MI in clinic.
- Subjects :
- Male
0301 basic medicine
Interleukin-1beta
Peroxisome Proliferator-Activated Receptors
Pharmaceutical Science
anti-apoptosis
Inflammation
Pharmacology
Article
NF-κB
Analytical Chemistry
Proinflammatory cytokine
lcsh:QD241-441
Electrocardiography
Mice
03 medical and health sciences
chemistry.chemical_compound
lcsh:Organic chemistry
Puerarin
In vivo
Drug Discovery
Animals
Medicine
Myocardial infarction
Physical and Theoretical Chemistry
Interleukin-6
Tumor Necrosis Factor-alpha
business.industry
puerarin-V
Organic Chemistry
Isoproterenol
NF-kappa B
Endothelial Cells
medicine.disease
Coronary Vessels
Isoflavones
anti-inflammation
Mice, Inbred C57BL
030104 developmental biology
myocardial infarction
chemistry
PPAR-Υ
Chemistry (miscellaneous)
Apoptosis
Heart failure
Molecular Medicine
medicine.symptom
business
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....9d18fd46ee382effde9312dd15a43ad4
- Full Text :
- https://doi.org/10.3390/molecules23123322