Berberine ameliorates renal injury in a rat model of D-galactose-induced aging through a PTEN/Akt-dependent mechanism

Arch Physiol Biochem. 2020 May;126(2):157-165. doi: 10.1080/13813455.2018.1499117. Epub 2018 Aug 25.

Abstract

This study aimed to investigate the protective effects of berberine (BBR) against D-galactose (D-gal)-induced renal aging in rats, pointing to its ability to modulate phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt signalling, and to attenuate oxidative stress, inflammation and apoptosis. Renal aging was induced by subcutaneous injection of D-gal for six consecutive weeks along with simultaneous oral administration of BBR and compared to control rats and rats received individual doses of either drug. BBR treatment significantly reduced the serum levels of urea and creatinine, retrieved the alterations in kidney histopathology, and restored redox balance evidenced by alleviations of the level of malondialdehyde, 8-hydroxy-2'-deoxyguanosine and activating heme oxygenase-1 enzyme. Moreover, it markedly reduced the serum levels of pro-inflammatory mediators, along with down-regulation of PTEN expression, enhanced Akt activity, as well as significantly higher immunostaining of the anti-apoptotic marker (Bcl-2). These findings hold a great promise for the use of BBR as a protecting agent against renal aging.

Keywords: D-galactose; PTEN/Akt; aging; berberine; oxidative stress.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine / blood
  • Administration, Oral
  • Aging / genetics*
  • Aging / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Apoptosis
  • Berberine / pharmacology*
  • Creatinine / blood
  • Galactose / toxicity
  • Gene Expression Regulation
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Inflammation
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Malondialdehyde / blood
  • Oxidative Stress / drug effects
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Renal Insufficiency / chemically induced
  • Renal Insufficiency / drug therapy*
  • Renal Insufficiency / genetics
  • Renal Insufficiency / metabolism
  • Signal Transduction
  • Urea / blood

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Bcl2 protein, rat
  • Proto-Oncogene Proteins c-bcl-2
  • Berberine
  • Malondialdehyde
  • 8-Hydroxy-2'-Deoxyguanosine
  • Urea
  • Creatinine
  • Heme Oxygenase-1
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • Pten protein, rat
  • Galactose