Korean red ginseng alleviates benign prostatic hyperplasia by dysregulating androgen receptor signaling and inhibiting DRP1-mediated mitochondrial fission

Background: Panax ginseng (C.A. Mey.) has traditionally been used in Korea and China to treat fatigue and digestive conditions. In particular, Korean red ginseng (KRG, produced from streamed and dried P. ginseng) exerts anti-aging and anti-inflammatory effects. However, the effects of KRG on benign prostatic hyperplasia (BPH), a representative aging-related disease, and the underlying mechanisms remain unclear. In this study, we investigate the therapeutic effects of KRG on BPH based on mitochondrial dynamics (fission and fusion). Methods: The effects of KRG on cell proliferation, apoptosis, and mitochondrial dynamics and morphology were evaluated in a rat model of testosterone propionate (TP)-induced BPH and TP-treated LNCaP cells, with mdivi-1. Results: KRG treatment reduced the levels of androgen receptors (AR) and prostate-specific antigens in the BPH group. KRG inhibited cell proliferation by reducing cyclin D and proliferation of cell nuclear antigen but induced apoptosis by increasing the ratio of B-cell lymphoma protein 2 (Bcl-2)- associated X to Bcl-2 expression. Notably, KRG treatment increased the phosphorylation of dynamin-related protein 1 (DRP-1, serine 637) compared with that in the BPH group, leading to the inhibition of mitochondrial fission and elongation of the mitochondria. Decreased cell proliferation and increased apoptosis were observed with KRG treatment. Conclusion: KRG dysregulated AR signaling and inhibited mitochondrial fission by increasing DRP-1 (ser637) phosphorylation, leading to decreased cell proliferation and induction of apoptosis. The regulation of mitochondrial dynamics by KRG demonstrates a potential clinical strategy for alleviating BPH.