Salvia miltiorrhiza protects against diabetic nephropathy through metabolome regulation and wnt/β-catenin and TGF-β signaling inhibition

Pharmacol Res. 2019 Jan:139:26-40. doi: 10.1016/j.phrs.2018.10.030. Epub 2018 Nov 3.

Abstract

Diabetic nephropathy (DN) is a complication of diabetes that is caused by uncontrolled high blood sugar. It has been reported that Salvia miltiorrhiza (SM) possesses the ability to prevent kidney damage, although the mechanisms remain unclear. The study was to investigate whether and how SM improved DN injury via regulation of metabolome and the molecular mechanisms. In this study, SD rats were fed a high glucose / high fat diet accompanied by 0.5% glucose water. Three weeks later, the rats were given one intraperitoneal injection of 30 mg/kg STZ each day for three days for DN model. The biochemical indicators and metabolomics of plasma, urine and renal tissue were analyzed. Then the western blotting analysis of renal tissue and glomerular mesangial cells were investigated. The results showed that Salvia miltiorrhiza extracts improved the renal injury and regulation of abnormal glycolipid metabolism. The metabolites in serum, urine and renal tissues have been changed significantly. The involved metabolic pathways mainly include phospholipid, arachidonic acid, and pyrimidine metabolisms. Meanwhile, SM inhibited the relative expression levels of wnt4, β-catenin and TGF-β in renal tissue and high-glucose induced glomerular mesangial cells.

Keywords: Diabetic nephropathy; Metabolome alterations; Salvia miltiorrhiza; wnt/β-catenin and TGF-βsignal pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Metabolome / drug effects*
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use*
  • Protective Agents / pharmacology*
  • Protective Agents / therapeutic use*
  • Rats, Sprague-Dawley
  • Salvia miltiorrhiza*
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism
  • Wnt Proteins / metabolism
  • beta Catenin / metabolism

Substances

  • Plant Extracts
  • Protective Agents
  • Transforming Growth Factor beta
  • Wnt Proteins
  • beta Catenin