Riligustilide Attenuated Renal Injury by the Blockade of Renin

Cell Physiol Biochem. 2018;50(2):654-667. doi: 10.1159/000494186. Epub 2018 Oct 11.

Abstract

Background/aims: Nephropathy related with renin can be alleviated with ACE-inhibitors or AT1R blockers, whereas they might be ineffective after long-term administration because of a feedback production of enhanced renin. Therefore, it is urgent to develop a new category of anti-nephropathy medicine directly targeting renin. Riligustilide (C20), originally isolated from the Chinese herb Ligusticumporteri, a rhizome, was confirmed effective against many diseases.

Methods: The therapeutic effect of C20 on renal injury and its underlying mechanism were investigated in three different nephrotic models, which were spontaneously hypertension rats (SHR) model, diabetic nephropathy in BTBR ob/ob mice model and 5/6-nephrectomized (5/6NX) rats model.

Results: The intensity of kidney fibrosis was extensively decreased in the C20-treated rats compared to the vehicle animals. C20 significantly alleviated renal injury much more in 5/6 NX rats than in vehicle group. The rats in 5/6 NX without administrated C20 developed albuminuria earlier with more severe symptoms. Additionally, our findings showed that C20 down-regulated the renin expression and relocation of CREB-CBP complex in vivo and in vitro.

Conclusion: C20 plays importantly reno-protective roles most likely through the relocation of CREB-CBP complex.

Keywords: CREB; Nephropathy; Renal Injury; Renin; Riligustilide.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Benzofurans / metabolism
  • Benzofurans / pharmacology*
  • Benzofurans / therapeutic use
  • CREB-Binding Protein / metabolism
  • Cell Line
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology*
  • Diabetic Nephropathies / prevention & control
  • Disease Models, Animal
  • Down-Regulation / drug effects*
  • Kidney / drug effects
  • Kidney / pathology
  • Male
  • Medicine, Chinese Traditional
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Obese
  • Molecular Docking Simulation
  • Nephrectomy
  • Phosphoproteins / metabolism
  • Rats
  • Rats, Inbred SHR
  • Renin / antagonists & inhibitors
  • Renin / metabolism*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Benzofurans
  • Membrane Proteins
  • Pag1 protein, rat
  • Phosphoproteins
  • riligustilide
  • CREB-Binding Protein
  • Crebbp protein, rat
  • Renin