The protective effects of polysaccharide extract from Xin-Ji-Er-Kang formula on Ang II-induced HUVECs injury, L-NAME-induced hypertension and cardiovascular remodeling in mice

BMC Complement Altern Med. 2019 Jun 13;19(1):127. doi: 10.1186/s12906-019-2539-z.

Abstract

Background: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection against cardiovascular diseases, including hypertension and myocarditis.

Methods: Cultured human umbilical vascular endothelial cells (HUVECs) were treated with angiotensin II (Ang II) and different concentrations of aqueous layer extracts (AqE). Subsequently nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) expression levels were detected. In addition, fifty Kunming mice were randomized into control, Nω-nitro-L-arginine methyl ester (L-NAME), L-NAME+AqE, L-NAME+XJEK and L-NAME+fosinopril treatment groups. Following 8 weeks of treatment, the cardiac hemodynamic index was measured, relaxation of the aorta was examined and pathological changes were observed. Colorimetric analysis and enzyme linked immunosorbent assay (ELISA) were applied to determine the relevant indicators in plasma and cardiac tissues.

Results: The in vitro study results demonstrated that AqE could preserve endothelial function (NO, 21.05 ± 2.03 vs. 8.64 ± 0.59; eNOS, 1.08 ± 0.17 vs.0.73 ± 0.06). In addition, the in vivo results demonstrated that compared with the control group, treatment with AqE could enhance a high hemodynamic state (left ventricular systolic pressure, 116.76 ± 9.96 vs.114.5 ± 15.16), improve endothelial function (NO, 7.98 ± 9.64 vs. 1.66 ± 3.11; eNOS, 19.78 ± 3.18 vs.19.38 ± 3.85), suppress oxidative stress (OS) (superoxide dismutase, 178.17 ± 13.78 vs. 159.38 ± 18.86; malondialdehyde, 0.77 ± 0.13 vs.1.25 ± 0.36) and reverse cardiovascular remodeling.

Conclusion: Polysaccharide from XJEK exerts protective effects against Ang II-induced injury in HUVECs and L-NAME-induced hypertension in mice and the underlying mechanism may be attributed to improving endothelial dysfunction, OS and the inflammation status in mice.

Keywords: Cardiac remodeling; Endothelial dysfunction; Hypertension; Inflammation; Oxidative stress.

MeSH terms

  • Angiotensin II
  • Animals
  • Aorta / drug effects
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Blood Pressure / drug effects
  • Cytokines / metabolism
  • Drug Evaluation, Preclinical
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / drug effects*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hypertension / chemically induced
  • Hypertension / drug therapy*
  • Inflammation / drug therapy
  • Male
  • Malondialdehyde / blood
  • Mice
  • Myocardium / metabolism
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / blood
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress / drug effects
  • Phytotherapy
  • Superoxide Dismutase / blood
  • Vascular Remodeling / drug effects*

Substances

  • Cytokines
  • Drugs, Chinese Herbal
  • xin-ji-er-kang
  • Angiotensin II
  • Nitric Oxide
  • Malondialdehyde
  • N,N-dimethylarginine
  • Arginine
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Superoxide Dismutase
  • NG-Nitroarginine Methyl Ester