Oleanolic Acid Ameliorates Benign Prostatic Hyperplasia by Regulating PCNA-Dependent Cell Cycle Progression In Vivo and In Vitro

J Nat Prod. 2020 Apr 24;83(4):1183-1189. doi: 10.1021/acs.jnatprod.9b01210. Epub 2020 Mar 19.

Abstract

Oleanolic acid (OA) is a natural, biologically active pentacyclic triterpenoid found in Cornus officinalis. Although C. officinalis and OA have antiproliferative actions, the effects and mechanisms of OA in benign prostatic hyperplasia (BPH) are unclear. We examined the effect of OA in an animal model of testosterone-induced BPH. Male rats were injected with testosterone propionate with or without OA. The inhibitory effect of OA on BPH-1 cells was determined in vitro. Rats with BPH exhibited outstanding BPH symptoms, including prostatic enlargement, upregulated dihydrotestosterone and 5α-reductase 2 levels, and histological changes. Compared with the BPH group, the OA group showed fewer pathological alterations and regular androgen events. OA inhibited prostate cell proliferation by downregulating the expression of proliferating cell nuclear antigen (PCNA) and cell cycle markers in BPH-induced animals. This indicated that OA has superior therapeutic effect in the BPH animal model than finasteride. In vitro studies demonstrated upregulation of PCNA and cell cycle proteins, whereas OA clearly reduced this upregulation. Thus, OA may inhibit the development of BPH by targeting cell cycle progression markers. These suggest that OA is a potential agent for BPH treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects
  • Humans
  • Male
  • Molecular Structure
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proliferating Cell Nuclear Antigen / pharmacology
  • Proliferating Cell Nuclear Antigen / therapeutic use*
  • Prostatic Hyperplasia / drug therapy*
  • Prostatic Hyperplasia / pathology
  • Rats
  • Testosterone / chemistry*
  • Testosterone / metabolism
  • Testosterone Propionate / adverse effects

Substances

  • Proliferating Cell Nuclear Antigen
  • Testosterone
  • Oleanolic Acid
  • Testosterone Propionate