Astragaloside IV protects against isoproterenol-induced cardiac hypertrophy by regulating NF-κB/PGC-1α signaling mediated energy biosynthesis.
We previously reported that Astragaloside IV (ASIV), a major active constituent of Astragalus membranaceus (Fisch) Bge protects against cardiac hypertrophy in rats induced by isoproterenol (Iso), however the mechanism underlying the protection remains unknown. Dysfunction of cardiac energy biosynthesis contributes to the hypertrophy and Nuclear Factor κB (NF-κB)/Peroxisome Proliferator-Activated Receptor-γ Coactivator 1α (PGC-1α) signaling gets involved in the dysfunction. The present study was designed to investigate the mechanism by which ASIV improves the cardiac hypertrophy with focuses on the NF-κB/PGC-1α signaling mediated energy biosynthesis. Sprague-Dawley (SD) rats or Neonatal Rat Ventricular Myocytes (NRVMs) were treated with Iso alone or in combination with ASIV. The results showed that combination with ASIV significantly attenuated the pathological changes, reduced the ratios of heart weight/body weight and Left ventricular weight/body weight, improved the cardiac hemodynamics, down-regulated mRNA expression of Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP), increased the ratio of ATP/AMP, and decreased the content of Free Fat Acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with ASIV significantly decreased the surface area and protein content, down-regulated mRNA expression of ANP and BNP, increased the ratio of ATP/AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, ASIV increased the protein expression of ATP5D, subunit of ATP synthase and PGC-1α, inhibited translocation of p65, subunit of NF-κB into nuclear fraction in both rats and NRVMs compared with Iso alone. Parthenolide (Par), the specific inhibitor of p65, exerted similar effects as ASIV in NRVMs. Knockdown of p65 with siRNA decreased the surface areas and increased PGC-1α expression of NRVMs compared with Iso alone. The results suggested that ASIV protects against Iso-induced cardiac hypertrophy through regulating NF-κB/PGC-1α signaling mediated energy biosynthesis.
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, Jinzhou, Liaoning, P.R. China.
Suping
S
Zhang
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, Jinzhou, Liaoning, P.R. China.
Futian
F
Tang
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, Jinzhou, Liaoning, P.R. China.
Yuhong
Y
Yang
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, Jinzhou, Liaoning, P.R. China.
Meili
M
Lu
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, Jinzhou, Liaoning, P.R. China.
Aina
A
Luan
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, Jinzhou, Liaoning, P.R. China.
Jing
J
Zhang
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, Jinzhou, Liaoning, P.R. China.
Juan
J
Yang
Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Drug Research Institute, Liaoning Medical University, Jinzhou, Liaoning, P.R. China.
Hongxin
H
Wang
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015536:Down-Regulation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000009:adverse effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000172:deficiency / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*
D016328:NF-kappa B; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012503:Saponins; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014315:Triterpenes; D020097:Natriuretic Peptide, Brain; C052064:astragaloside A; D009320:Atrial Natriuretic Factor; D007545:Isoproterenol