Galangin alleviates vascular dysfunction and remodelling through modulation of the TNF-R1, p-NF-κB and VCAM-1 pathways in hypertensive rats

Life Sci. 2021 Nov 15:285:119965. doi: 10.1016/j.lfs.2021.119965. Epub 2021 Sep 17.

Abstract

Galangin is a natural flavonoid isolated from ginger, honey and propolis.

Aims: To investigate the effect of galangin on blood pressure, vascular changes, sympathoexcitation, oxidative stress and inflammation in rats treated with NG-nitro-l-arginine methyl ester (l-NAME).

Materials and methods: Male Wistar rats (220-250 g) were given l-NAME (0.5 mg/mL in drinking water) to induce hypertension for 5 weeks. They were treated with vehicle, galangin (30 or 60 mg/kg), or amlodipine (10 mg/kg) for the final two weeks (n = 6/group).

Key findings: Galangin significantly reduced blood pressure and improved the impairment of endothelium-dependent vasodilation in hypertensive rats. Sympathoexcitation, including enhancement of contractile responses to electrical field stimulation, increases in intensity of tyrosine hydroxylase and plasma norepinephrine concentration in hypertensive rats, was attenuated by galangin treatment. Galangin also reduced systemic and vascular oxidative damage and increased plasma nitric oxide levels in the hypertensive groups. Aortic remodelling accompanied by aortic wall hypertrophy and fibrosis observed in hypertensive rats were alleviated by galangin treatment. Furthermore, galangin exhibited an anti-inflammatory effect by suppressing the upregulation of tumour necrosis factor receptor 1 (TNF-R1), phospho-nuclear factor kappa B (p-NF-κB) and vascular cell adhesion protein 1 (VCAM-1) in aortic tissue and reducing plasma tumour necrosis factor alpha (TNF-α) in l-NAME rats. In conclusion, galangin had antihypertensive effects that were relevant to attenuating endothelial dysfunction, sympathoexcitation and vascular remodelling. These effects might be contributed by antioxidant and anti-inflammatory capacities and modulation of the TNF-R1, p-NF-κB and VCAM-1 pathways in hypertensive rats.

Keywords: Galangin; Hypertension; Oxidative stress and inflammation; Sympathoexcitation; Vascular dysfunction and remodelling.

MeSH terms

  • Amlodipine / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antihypertensive Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Blood Pressure / drug effects
  • Flavonoids / pharmacology*
  • Hypertension / metabolism*
  • Male
  • NF-kappa B / metabolism*
  • NG-Nitroarginine Methyl Ester
  • Rats
  • Rats, Wistar
  • Receptors, Tumor Necrosis Factor, Type I / metabolism*
  • Vascular Cell Adhesion Molecule-1 / metabolism*
  • Vascular Remodeling / drug effects*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antihypertensive Agents
  • Antioxidants
  • Flavonoids
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor, Type I
  • Tnfrsf1a protein, rat
  • Vascular Cell Adhesion Molecule-1
  • galangin
  • Amlodipine
  • NG-Nitroarginine Methyl Ester