Salvianolic acid A as a multifunctional agent ameliorates doxorubicin-induced nephropathy in rats

Sci Rep. 2015 Jul 21:5:12273. doi: 10.1038/srep12273.

Abstract

Nephrotic syndrome (NS) is still a therapeutic challenge. To date there is no ideal treatment. Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury. Salvianolic acid A (SAA) is the major active component of Salviae Miltiorrhizae Bunge. Previous studies have demonstrated that SAA is a multi-target agent and has various pharmacological activities. The pleiotropic properties of SAA predict its potential in the treatment of NS. The study investigated the effect of SAA on doxorubicin-induced nephropathy. The kidney function related-biochemical changes, hemorheological parameters and oxidative stress status were determined, and histological examination using light and transmission electron microcopies and western blot analysis were also performed. Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology. Furthermore, SAA restored podocin expression, down-regulated the expression of NF-κB p65 and p-IκBα while up-regulating IκBα protein expression. Overall, as a multifunctional agent, SAA has a favorable renoprotection in doxorubicin-induced nephropathy. The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects. All these indicate that SAA is likely to be a promising agent for NS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeic Acids / therapeutic use*
  • Doxorubicin / adverse effects*
  • Hemorheology / drug effects
  • I-kappa B Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / ultrastructure
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / complications
  • Kidney Diseases / drug therapy*
  • Lactates / therapeutic use*
  • Male
  • Malondialdehyde / metabolism
  • Membrane Proteins / metabolism
  • NF-KappaB Inhibitor alpha
  • Oxidative Stress / drug effects
  • Phosphorylation
  • Podocytes / drug effects
  • Podocytes / pathology
  • Podocytes / ultrastructure
  • Proteinuria / complications
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism
  • Time Factors
  • Transcription Factor RelA / metabolism

Substances

  • Caffeic Acids
  • I-kappa B Proteins
  • Intracellular Signaling Peptides and Proteins
  • Lactates
  • Membrane Proteins
  • NPHS2 protein
  • Nfkbia protein, rat
  • Transcription Factor RelA
  • NF-KappaB Inhibitor alpha
  • Malondialdehyde
  • salvianolic acid A
  • Doxorubicin
  • Superoxide Dismutase