Park Hee-Seon, Seo Chang-Seob, Wijerathne Charith Ub, Jeong Hye-Yun, Moon Og-Sung, Seo Young-Won, Won Young-Suk, Son Hwa-Young, Lim Jong-Hwan, Kwun Hyo-Jung
Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University.
K-herb Research Center, Korea Institute of Oriental Medicine.
Biol Pharm Bull. 2019 Jan 1;42(1):1-9. doi: 10.1248/bpb.b18-00313. Epub 2018 Nov 1.
Veratrum maackii (VM), a perennial plant in the Melanthiaceae family, has anti-hypertensive, anti-cholinergic, anti-asthmatic, anti-tussive, anti-fungal, anti-melanogenesis, and anti-tumor activities. Here, we investigated the therapeutic effect of VM on benign prostatic hyperplasia (BPH) in human normal prostate cell line (WPMY-1) and a testosterone propionate-induced BPH animal model. WPMY-1 cells were treated with VM (1-10 µg/mL) and testosterone propionate (100 nM). BPH in rats was generated via daily subcutaneous injections of testosterone propionate (3 mg/kg) dissolved in corn oil, for 4 weeks. VM (150 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the testosterone propionate. All rats were sacrificed and the prostates were dissected, weighed, and subjected to histological, immunohistochemical, and biochemical examinations. Immunoblotting experiments indicated that WPMY-1 cells treated testosterone propionate had increased expression of prostate specific antigen (PSA) and androgen receptor (AR), and treatment with VM or finasteride blocked this effect. In rat model, VM significantly reduced prostate weight, prostatic hyperplasia, prostatic levels of dihydrotestosterone (DHT), and expression of proliferation markers such as proliferating cell nuclear antigen (PCNA) and cyclin D1, but increased the expression of pro-apoptotic Bcl-2-associated X protein (Bax) and the cleavage of caspase-3. VM administration also suppressed the testosterone propionate-induced activation of nuclear factor-kappaB (NF-κB). Our results indicate that VM effectively represses the development of testosterone propionate-induced BPH, suggesting it may be a useful treatment agent for BPH.
藜芦(VM)是藜芦科的一种多年生植物,具有抗高血压、抗胆碱能、抗哮喘、止咳、抗真菌、抗黑色素生成和抗肿瘤活性。在此,我们研究了VM对人正常前列腺细胞系(WPMY-1)和丙酸睾酮诱导的良性前列腺增生(BPH)动物模型中BPH的治疗作用。用VM(1-10μg/mL)和丙酸睾酮(100 nM)处理WPMY-1细胞。通过每日皮下注射溶解于玉米油中的丙酸睾酮(3 mg/kg),持续4周,诱导大鼠发生BPH。在给予丙酸睾酮的同时,通过口服灌胃每日给予VM(150 mg/kg),持续4周。处死所有大鼠,解剖前列腺,称重,并进行组织学、免疫组织化学和生化检查。免疫印迹实验表明,用丙酸睾酮处理的WPMY-1细胞中前列腺特异性抗原(PSA)和雄激素受体(AR)的表达增加,而用VM或非那雄胺处理可阻断这种作用。在大鼠模型中,VM显著降低了前列腺重量、前列腺增生、前列腺组织中双氢睾酮(DHT)的水平以及增殖标志物如增殖细胞核抗原(PCNA)和细胞周期蛋白D1的表达,但增加了促凋亡蛋白Bcl-2相关X蛋白(Bax)的表达和半胱天冬酶-3的裂解。给予VM还抑制了丙酸睾酮诱导的核因子-κB(NF-κB)的激活。我们的结果表明,VM有效地抑制了丙酸睾酮诱导的BPH的发展,提示它可能是一种治疗BPH的有效药物。