Chrysophanic acid reduces testosterone-induced benign prostatic hyperplasia in rats by suppressing 5α-reductase and extracellular signal-regulated kinase

Oncotarget. 2017 Feb 7;8(6):9500-9512. doi: 10.18632/oncotarget.13430.

Abstract

Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in male population, of which incidence increases gradually with age. In this study, we investigated the effect of chrysophanic acid (CA) on BPH. BPH was induced by a 4-week injection of testosterone propionate (TP). Four weeks of further injection with vehicle, TP, TP + CA, TP + finasteride was carried on. In the CA treatment group, the prostate weight was reduced and the TP-induced histological changes were restored as the normal control group. CA treatment suppressed the TP-elevated prostate specific antigen (PSA) expression. In addition, 5α-reductase, a crucial factor in BPH development, was suppressed to the normal level close to the control group by CA treatment. The elevated expressions of androgen receptor (AR), estrogen receptor α and steroid receptor coactivator 1 by TP administration were also inhibited in the CA group when compared to the TP-induced BPH group. Then we evaluated the changes in three major factors of the mitogen-activated protein kinase chain during prostatic hyperplasia; extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38). While ERK was elevated in the process of BPH, JNK and p38 was not changed. This up-regulated ERK was also reduced as normal by CA treatment. Further in vitro studies with RWPE-1 cells confirmed TP-induced proliferation and elevated AR, PSA and p-ERK were all reduced by CA treatment. Overall, these results suggest a potential pharmaceutical feature of CA in the treatment of BPH.

Keywords: 5α-reductase; benign prostatic hyperplasia-BPH; chrysophanic acid; extracellular signal-regulated kinase; prostate specific antigen.

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism*
  • 5-alpha Reductase Inhibitors / pharmacology*
  • Animals
  • Anthraquinones / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects*
  • Disease Models, Animal
  • Down-Regulation
  • Estrogen Receptor alpha / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Finasteride / pharmacology
  • Male
  • Nuclear Receptor Coactivator 1 / metabolism
  • Organ Size
  • Phosphorylation
  • Prostate / drug effects*
  • Prostate / enzymology
  • Prostate / pathology
  • Prostate-Specific Antigen / metabolism
  • Prostatic Hyperplasia / chemically induced
  • Prostatic Hyperplasia / enzymology
  • Prostatic Hyperplasia / pathology
  • Prostatic Hyperplasia / prevention & control*
  • Rats, Sprague-Dawley
  • Receptors, Androgen / metabolism
  • Signal Transduction / drug effects
  • Testosterone Propionate*
  • Time Factors

Substances

  • 5-alpha Reductase Inhibitors
  • Anthraquinones
  • Estrogen Receptor alpha
  • Receptors, Androgen
  • Finasteride
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • Nuclear Receptor Coactivator 1
  • Extracellular Signal-Regulated MAP Kinases
  • Prostate-Specific Antigen
  • chrysophanic acid
  • Testosterone Propionate