Effects of asiaticoside on levels of podocyte cytoskeletal proteins and renal slit diaphragm proteins in adriamycin-induced rat nephropathy

Life Sci. 2013 Sep 3;93(8):352-8. doi: 10.1016/j.lfs.2013.07.010. Epub 2013 Jul 18.

Abstract

Aims: Centella asiatica has been used to treat kidney diseases in Chinese traditional medicine. Asiaticoside (an extraction of C. asiatica) exerts a variety of pharmacological effects including immunomodulatory and anti-inflammatory functions. However, the mechanism of asiaticoside in the treatment of renal diseases remains largely unknown. This study investigated the molecular mechanism of asiaticoside in treating adriamycin-induced nephropathy of rats.

Main methods: Sixty-two SD male rats were randomly divided into normal control group (n=12) and nephropathy group (n=50). Except for the normal control group, rats were injected with adriamycin (6mg/kg) via the tail vein to induce nephropathy. Adriamycin induced nephropathic rats were divided into untreated group, prednisone group (25mg/kg), and asiaticoside groups with various dosages (8, 16 and 32mg/kg). Samples of urine and serum, tissue of kidney were collected for analysis after treatments for four weeks. Morphological changes were evaluated under light microscope and electron microscope. Synaptopodin, desmin, nephrin and podocin mRNA and protein were determined by RT-PCR and Western blotting.

Key findings: Compared to the untreated nephropathy group, asiaticoside treatment mitigated histological damages, decreased 24-hour urine protein excretion and total cholesterol, increased serum albumin. Asiaticoside treatment increased the mRNA and protein levels of synaptopodin, nephrin and podocin in a dose-dependent manner. Furthermore, asiaticoside treatment decreased the mRNA and protein levels of desmin.

Significance: Asiaticoside can mitigate adriamycin-induced nephropathy in rats, which is associated with the increase in synaptopodin, nephrin and podocin gene expression, and the decrease in desmin gene expression.

Keywords: Adriamycin-induced nephropathy; Asiaticoside; Desmin; Nephrin; Podocin; Synaptopodin.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / toxicity
  • Blotting, Western
  • Centella / chemistry*
  • Cytoskeletal Proteins / drug effects*
  • Cytoskeletal Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Doxorubicin / toxicity*
  • Gene Expression Regulation / drug effects
  • Kidney Diseases / chemically induced
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / physiopathology
  • Male
  • Medicine, Chinese Traditional / methods
  • Membrane Proteins / drug effects
  • Membrane Proteins / metabolism
  • Microscopy / methods
  • Podocytes / drug effects
  • Podocytes / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triterpenes / administration & dosage
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*

Substances

  • Antibiotics, Antineoplastic
  • Cytoskeletal Proteins
  • Membrane Proteins
  • RNA, Messenger
  • Triterpenes
  • Doxorubicin
  • asiaticoside