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

IF 4 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Chinese Journal of Natural Medicines Pub Date : 2024-07-01 DOI:10.1016/S1875-5364(24)60671-0
WEI Mengsha , SUN Weiguang , LIU Linlin , LI Yongqi , LI Lanqin , LI Qin , CHEN Yu , GUO Jieru , GU Lianghu , ZHU Hucheng , CHEN Chunmei , ZHANG Yonghui
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Abstract

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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高丽红参通过失调雄激素受体信号传导和抑制DRP1介导的线粒体分裂来缓解良性前列腺增生症。
在韩国和中国,传统上一直使用人参(C.A. Mey.)来缓解疲劳和消化系统疾病。特别是由人参提取的高丽红参(KRG)具有抗衰老和消炎的功效。然而,它对良性前列腺增生症(BPH)这种与衰老有关的代表性疾病的影响及其内在机制仍不清楚。本研究旨在阐明 KRG 对良性前列腺增生症的治疗效果,尤其关注线粒体动力学,包括裂变和融合过程。在丙酸睾酮(TP)诱导的良性前列腺增生大鼠模型和 TP 处理的 LNCaP 细胞中,以 mdivi-1 作为对照,评估了 KRG 对细胞增殖、凋亡、线粒体动力学和形态学的影响。结果显示,KRG 处理可降低良性前列腺增生组雄激素受体(AR)和前列腺特异性抗原的水平。KRG通过下调细胞周期蛋白D和增殖细胞核抗原(PCNA)水平抑制细胞增殖,并通过增加B细胞淋巴瘤蛋白2(Bcl-2)相关X蛋白(Bax)与Bcl-2的表达比例促进细胞凋亡。值得注意的是,与 BPH 组相比,KRG 处理增强了动态相关蛋白 1(DRP-1,丝氨酸 637)的磷酸化,从而抑制了线粒体裂变并导致线粒体伸长。线粒体动力学的这种调节与细胞增殖减少和凋亡增加有关。KRG 通过增强 DRP-1(ser637)磷酸化来失调 AR 信号并抑制线粒体裂变,从而有效减少细胞增殖并诱导细胞凋亡。这些研究结果表明,KRG 对线粒体动力学的调节为治疗良性前列腺增生症提供了一种前景广阔的临床方法。
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来源期刊
Chinese Journal of Natural Medicines
Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY
CiteScore
7.50
自引率
4.30%
发文量
2235
期刊介绍: The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.
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