Panax ginseng (C.A. Mey.) has been traditionally employed in Korea and China to alleviate fatigue and digestive disorders. In particular, Korean red ginseng (KRG), derived from streamed and dried P. ginseng, is known for its anti-aging and anti-inflammatory properties. However, its effects on benign prostatic hyperplasia (BPH), a representative aging-related disease, and the underlying mechanisms remain unclear. This study aims to elucidate the therapeutic effects of KRG on BPH, with a particular focus on mitochondrial dynamics, including fission and fusion processes. 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 as a control. The results revealed that KRG treatment reduced the levels of androgen receptors (AR) and prostate-specific antigens in the BPH group. KRG inhibited cell proliferation by downregulating cyclin D and proliferating cell nuclear antigen (PCNA) levels, and it promoted apoptosis by increasing the ratio of B-cell lymphoma protein 2 (Bcl-2)-associated X protein (Bax) to Bcl-2 expression. Notably, KRG treatment enhanced the phosphorylation of dynamin-related protein 1 (DRP-1, serine 637) compared with that in the BPH group, which inhibited mitochondrial fission and led to mitochondrial elongation. This modulation of mitochondrial dynamics was associated with decreased cell proliferation and increased apoptosis. By dysregulating AR signaling and inhibiting mitochondrial fission through enhanced DRP-1 (ser637) phosphorylation, KRG effectively reduced cell proliferation and induced apoptosis. These findings suggest that KRG’s regulation of mitochondrial dynamics offers a promising clinical approach for the treatment of BPH.
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