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甘草酸在良性前列腺增生中通过 5α-还原酶调节和细胞凋亡的治疗作用。

Therapeutic role of Glycyrrhiza Uralensis fisher on benign prostatic hyperplasia through 5 alpha reductase regulation and apoptosis.

机构信息

Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.

Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea; Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.

出版信息

Phytomedicine. 2022 Oct;105:154371. doi: 10.1016/j.phymed.2022.154371. Epub 2022 Jul 31.

Abstract

BACKGROUND

Benign prostatic hyperplasia (BPH) is an age-related disease in adult men. There are two pharmacological treatments for BPH. However, these synthetic materials have various risks, many studies are being conducted to develop new drugs from natural sources.

PURPOSE

In this study, we proposed a beneficial effect of Glycyrrhiza uralensis Fischer on the development and progression of BPH, focusing on the androgen receptor (AR) and 5α-reductase 2 (5AR2) signaling axis.

METHODS

To explain the therapeutic efficacy of a water extract of G. uralensis (GUWE) for BPH, we used testosterone propionate (TP)-induced BPH rat models and TP-treated RWPE-1 human prostate epithelial cells.

RESULTS

In the TP-induced BPH rat models, GUWE reduced the enlarged prostate weight, prostate index, prostate epithelial thickness, and serum DHT levels. In addition, the protein levels of AR and 5AR2 in prostate tissues were significantly decreased by GUWE treatment. Furthermore, GUWE induced apoptosis signaling through an increase of Bcl-2 associated X protein (Bax), caspase 3, and Poly (ADP-ribose) polymerase (PARP) and a decrease of B-cell lymphoma-extra-large (Bcl-xL) in prostate tissues of TP-induced BPH rats. These findings were also confirmed in TP-treated RWPE-1 cells. Fi treatment markedly decreased the sperm count in the epididymis of BPH rats, but GUWE treatment did not affect the sperm count, suggesting less toxicity.

CONCLUSION

These findings suggested that GUWE reduces the development of BPH by inhibiting AR-5AR2 and activating the apoptosis signaling pathway. Furthermore, unlike finasteride, GUWE did not affect sperm count. Therefore, we suggest that GUWE has a potential as a safer alternative option for BPH treatment.

摘要

背景

良性前列腺增生(BPH)是成年男性的一种与年龄相关的疾病。有两种治疗 BPH 的药理学方法。然而,这些合成材料存在各种风险,因此许多研究正在从天然来源开发新药物。

目的

在这项研究中,我们提出了甘草(Glycyrrhiza uralensis Fischer)对 BPH 发展和进展的有益影响,重点关注雄激素受体(AR)和 5α-还原酶 2(5AR2)信号轴。

方法

为了解释甘草水提取物(GUWE)治疗 BPH 的疗效,我们使用了丙酸睾酮(TP)诱导的 BPH 大鼠模型和 TP 处理的 RWPE-1 人前列腺上皮细胞。

结果

在 TP 诱导的 BPH 大鼠模型中,GUWE 降低了前列腺重量、前列腺指数、前列腺上皮厚度和血清 DHT 水平。此外,GUWE 处理显著降低了前列腺组织中 AR 和 5AR2 的蛋白水平。此外,GUWE 通过增加 B 细胞淋巴瘤-extra-large(Bcl-xL)蛋白水平诱导前列腺组织中的凋亡信号,通过增加 Bax、caspase 3 和聚(ADP-核糖)聚合酶(PARP)蛋白水平诱导前列腺组织中的凋亡信号。在 TP 处理的 RWPE-1 细胞中也证实了这些发现。Fi 处理显著降低了 BPH 大鼠附睾中的精子数,但 GUWE 处理并未影响精子数,提示毒性较小。

结论

这些发现表明,GUWE 通过抑制 AR-5AR2 和激活凋亡信号通路来减少 BPH 的发展。此外,与非那雄胺不同,GUWE 不影响精子数。因此,我们认为 GUWE 作为 BPH 治疗的更安全替代方案具有潜力。

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