Curcumin ameliorates hypertension via gut-brain communication in spontaneously hypertensive rat

Toxicol Appl Pharmacol. 2021 Oct 15:429:115701. doi: 10.1016/j.taap.2021.115701. Epub 2021 Aug 25.

Abstract

Gut dysbiosis and dysregulation of gut-brain communication have been identified in hypertensive patients and animal models. Previous studies have shown that probiotic or prebiotic treatments exert positive effects on the pathophysiology of hypertension. This study aimed to examine the hypothesis that the microbiota-gut-brain axis is involved in the antihypertensive effects of curcumin, a potential prebiotic obtained from Curcuma longa. Male 8- to 10-week-old spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were divided into four groups: WKY rats and SHRs treated with vehicle and SHRs treated with curcumin in dosage of 100 or 300 mg/kg/day for 12 weeks. Our results show that the elevated blood pressure of SHRs was markedly decreased in both curcumin-treated groups. Curcumin treatment also altered the gut microbial composition and improved intestinal pathology and integrity. These factors were associated with reduced neuroinflammation and oxidative stress in the hypothalamus paraventricular nucleus (PVN). Moreover, curcumin treatment increased butyrate levels in the plasma, which may be the result of increased butyrate-producing gut microorganisms. In addition, curcumin treatment also activated G protein-coupled receptor 43 (GPR 43) in the PVN. These results indicate that curcumin reshapes the composition of the gut microbiota and ameliorates the dysregulation of the gut-brain communication to induce antihypertensive effects.

Keywords: Butyrate; Curcumin; Gut microbiota; Gut–brain axis; Hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antihypertensive Agents / pharmacology*
  • Antioxidants / pharmacology
  • Bacteria / drug effects*
  • Bacteria / growth & development
  • Bacteria / metabolism
  • Blood Pressure / drug effects*
  • Brain-Gut Axis / drug effects*
  • Butyrates / blood
  • Cardiomegaly / metabolism
  • Cardiomegaly / microbiology
  • Cardiomegaly / physiopathology
  • Cardiomegaly / prevention & control
  • Curcumin / pharmacology*
  • Disease Models, Animal
  • Dysbiosis
  • Gastrointestinal Microbiome / drug effects*
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypertension / microbiology
  • Hypertension / physiopathology
  • Inflammation Mediators / metabolism
  • Male
  • Oxidative Stress / drug effects
  • Paraventricular Hypothalamic Nucleus / drug effects*
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Paraventricular Hypothalamic Nucleus / physiopathology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antihypertensive Agents
  • Antioxidants
  • Butyrates
  • Ffar2 protein, rat
  • Inflammation Mediators
  • Receptors, G-Protein-Coupled
  • Curcumin