Sodium houttuyfonate protects against cardiac injury by regulating cardiac energy metabolism in diabetic rats

Eur J Pharmacol. 2022 Oct 15:932:175236. doi: 10.1016/j.ejphar.2022.175236. Epub 2022 Aug 28.

Abstract

Diabetic cardiomyopathy is a diabetic complication with complicated pathophysiological changes and pathogenesis and difficult treatment. Sodium houttuyfonate is the adduct of sodium bisulfite and houttuynin, the main volatile component in Houttuynia cordata Thunb, possesses a variety of activities including multiple interventions on inhibiting ventricular remodeling. The study aims to explore effect of sodium houttuyfonate on diabetic myocardial injury and its underlying mechanisms. The diabetes model was established by intraperitoneal injection of streptozotocin at a dose of 85 mg/kg. By intragastric administration for 26 days, sodium houttuyfonate (50 and 100 mg/kg/d) reversed the abnormal serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, improved the abnormal levels of serum aspartate aminotransferase and brain natriuretic peptide, reduced electrocardiogram P-R and QRS interval extension, accelerated the heart rate, decreased serum malondialdehyde content, up-regulated the myocardial energy metabolism including elevated the contents of ATP, ADP, total adenine nucleotides and phosphocreatine in myocardium, decreased AMP/ATP ratio, elevated myocardial Ca2+-Mg2+-ATPase activity, and down-regulated the mRNA expressions of AMP protein activation kinase α2 (AMPK-α2) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). In a conclusion, these results suggest that sodium houttuyfonate can improve cardiac energy metabolism disorder caused by diabetes by increasing cardiac Ca2+-Mg2+-ATPase activity and regulating AMPK signaling pathway, and then attenuates cardiac injury caused by hyperglycemia. In addition, sodium houttuyfonate also has the effects of anti-oxidation and improving abnormal levels of blood lipid.

Keywords: AMPK-α(2); Diabetes; Energy metabolism; Myocardial injury; PGC-1α; Sodium houttuyfonate.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adenosine Diphosphate / metabolism
  • Adenosine Monophosphate
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Alkanes
  • Animals
  • Aspartate Aminotransferases / metabolism
  • Cholesterol
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / drug therapy
  • Energy Metabolism
  • Heart Injuries* / drug therapy
  • Heart Injuries* / prevention & control
  • Lipoproteins, HDL
  • Lipoproteins, LDL / metabolism
  • Malondialdehyde
  • Natriuretic Peptide, Brain / metabolism
  • PPAR gamma / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Phosphocreatine / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin
  • Sulfites
  • Triglycerides

Substances

  • Alkanes
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • RNA, Messenger
  • Sulfites
  • Triglycerides
  • sodium houttuyfonate
  • Phosphocreatine
  • Natriuretic Peptide, Brain
  • Adenosine Monophosphate
  • Malondialdehyde
  • Streptozocin
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Cholesterol
  • Aspartate Aminotransferases
  • AMP-Activated Protein Kinases
  • Adenosine Triphosphatases