Red ginseng and 20(S)-Rg3 control testosterone-induced prostate hyperplasia by deregulating androgen receptor signaling

Abstract

Since prostate growth is governed by the androgen signaling pathway, blockade of the pathway is regarded as an appropriate strategy for the treatment of benign prostatic hyperplasia (BPH). Panax ginseng is known to have various pharmacological activities. Of several products of its root, red ginseng, having many bioactive ginsenosides, is most popularly used in Korea, and recently has been reported to control the proliferation of cancer cells. We here tested the effect of a water extract of Korean red ginseng (WKRG) on testosterone-induced prostate hyperplasia. WKRG (daily intraperitoneal injection) prevented prostate overgrowth and epithelial thickening induced by testosterone in rats, and suppressed a rat prostate kallikrein-S3. In human prostate cells, WKRG inhibited testosterone-induced cell proliferation, arrested cell cycle by inducing p21 and p27, and induced apoptosis. Testosterone-induced expression of human kallikrein-3 mRNA and activation of androgen receptor (AR) were effectively inhibited by WKRG. Of the major ginsenosides included in WKRG, 20(S)-Rg3 was identified to repress AR activity and to attenuate prostate cell growth during testosterone stimulation. Moreover, 20(S)-Rg3 downregulated AR by facilitating the degradation of AR protein. WKRG and 20(S)-Rg3 were found to have new pharmacological activities against testosterone-induced prostate overgrowth. Given that red ginseng has been used safely in Asia for 1000 years, red ginseng and 20(S)-Rg3 could be potential therapeutic regimens for treating BPH.

Ginsenoside 20(S)-Rg3 Targets HIF-1α to Block Hypoxia-Induced Epithelial-Mesenchymal Transition in Ovarian Cancer Cells

“…This paucity of 20(S)-Rg3 targets hinders the elucidation of precise upstream signaling events leading to the inhibition of hypoxia-induced EMT, and poses technical challenges to structure-based function improvement of 20(S)-Rg3 for even better therapeutic efficacy in vivo . Moreover, since 20(S)-Rg3 is active against a variety of human cancers [29], [30], [45], it remains to be seen whether or not this ginsenoside also blocks EMT in other well-characterized tumor models. Our work reported here lays ground for necessary additional studies of this existing compound to warrant its clinical use as a new anti-cancer drug for the treatment of various metastatic diseases including ovarian cancer.…”

Lycopersicon esculentum Extract Enhances Cognitive Function and Hippocampal Neurogenesis in Aged Mice

“…A western blot analysis was performed as previously described [20]. The protein quantity was determined using a bicinchoninic acid (BCA) reagent (Sigma-Aldrich).…”

Red Ginseng Extract Promotes the Hair Growth in Cultured Human Hair Follicles

“…6 Ginsenoside-Rg3 reportedly inhibits the transcriptional activities of androgen receptors and downregulates androgen receptors in a prostate cancer cell line. 7 Several murine studies support the hypothesis that ginseng and its ginsenosides may promote hair growth. [8][9][10] The administration of ginseng suppresses apoptosis in hair follicles in irradiated mice.…”