Effects of steroidal saponins extract from Ophiopogon japonicus root ameliorates doxorubicin-induced chronic heart failure by inhibiting oxidative stress and inflammatory response

Pharm Biol. 2019 Dec;57(1):176-183. doi: 10.1080/13880209.2019.1577467.

Abstract

Context: Ophiopogonis Radix, the root of Ophiopogon japonicus (Thunb.) Ker-Gawl (Liliaceae), is a Traditional Chinese Medicine, which has been investigated to possess effective treatment of cardiovascular diseases.

Objective: This study evaluates the cardioprotective effects of steroidal saponins extract from Ophiopogon japonicus (SOJ) root against doxorubicin-induced chronic heart failure (CHF) through the amelioration of oxidative stress and inflammation.

Materials and methods: A Sprague-Dawley rat model of CHF was established by intraperitoneally injected with DOX. All rats were randomly divided into four groups: Control group, CHF group, CHF + SOJ (100 mg/kg) treatment group, SOJ (100 mg/kg) treatment group (n = 8/group). After six weeks administration, biometric and echocardiography were measured. The levels of biochemical parameters were measured using commercial kits.

Results: The values of LVESP, +dP/dtmax, -dP/dtmax, EF and FS increased to 116.20 ± 1.68 mmHg, 2978.71 ± 168.26 mmHg/s, 3452.61 ± 286.09 mmHg/s, 68.26 ± 5.28% and 31.97 ± 3.79%, respectively; the values of LVEDP, LVESD and LVEDD decreased to 8.85 ± 0.84 mmHg, 8.39 ± 0.45 mm and 12.36 ± 0.87 mm in CHF + SOJ group. In addition, the levels of IL-6, TNF-α and IL-1β decreased to 154.41 ± 7.72 pg/mg protein, 110.02 ± 6.96 pg/mg protein and 39.39 ± 5.27 pg/mg protein, respectively; the relative activity of p38 MAPK decreased to 2.60 ± 0.40 in CHF + SOJ group. Furthermore, the activities of SOD, CAT and GSH-Px increased to 268.77 ± 6.20 U/mg protein, 13.68 ± 0.68 U/mg protein and 316.90 ± 8.08 µmol/mg protein, and the content of MDA decreased to 4.03 ± 0.43 nmol/mg protein in CHF + SOJ group.

Conclusions: SOJ exerts the cardioprotective effect against DOX-induced CHF through suppressing inflammatory and oxidative stress. These results provide evidence that SOJ might be an effective treatment for CHF.

Keywords: Cardiovascular diseases; antioxidant effect; cardiotoxicity; inflammatory cytokines.

MeSH terms

  • Animals
  • Cardiotonic Agents / isolation & purification
  • Cardiotonic Agents / pharmacology*
  • Chronic Disease
  • Doxorubicin / toxicity
  • Echocardiography
  • Heart Failure / chemically induced
  • Heart Failure / prevention & control*
  • Inflammation / chemically induced
  • Inflammation / prevention & control
  • Male
  • Medicine, Chinese Traditional / methods
  • Ophiopogon / chemistry*
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Saponins / isolation & purification
  • Saponins / pharmacology*
  • Steroids / isolation & purification
  • Steroids / pharmacology

Substances

  • Cardiotonic Agents
  • Plant Extracts
  • Saponins
  • Steroids
  • Doxorubicin