Ub Wijerathne Charith, Park Hee-Seon, Jeong Hye-Yun, Song Ji-Won, Moon Og-Sung, Seo Young-Won, Won Young-Suk, Son Hwa-Young, Lim Jong-Hwan, Yeon Sung-Hum, Kwun Hyo-Jung
Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University.
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology.
Biol Pharm Bull. 2017 Dec 1;40(12):2125-2133. doi: 10.1248/bpb.b17-00468. Epub 2017 Sep 22.
Quisqualis indica (QI) has been used for treating disorders such as stomach pain, constipation, and digestion problem. This study was aimed to evaluate the therapeutic efficacy of QI extract on treating benign prostatic hyperplasia (BPH) in LNCaP human prostate cancer cell line and a testosterone-induced BPH rat model. LNCaP cells were treated with QI plus testosterone propionate (TP), and androgen receptor (AR) and prostate specific antigen (PSA) expression levels were assessed by Western blotting. To induce BPH, the rats were subjected to a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks. The rats in treatment group were orally gavaged with QI (150 mg/kg) together with the TP injection. In-vitro studies showed that TP-induced increases in AR and PSA expression in LNCaP cells were reduced by QI treatment. In BPH-model rats, the prostate weight, testosterone in serum, dihydrotestosterone (DHT) concentration and 5α-reductase type 2 mRNA expression in prostate tissue were significantly reduced following the treatment with QI. TP-induced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 were significantly attenuated in QI-treated rats. In addition, QI induced apoptosis by up-regulating caspase-3 and -9 activity and decreasing the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio in prostate tissues of BPH rats. Further investigation showed that TP-induced activation of AKT and glycogen synthase kinase 3β (GSK3β) was reduced by QI administration. Therefore, our findings suggest that QI attenuates the BPH state in rats through anti-proliferative and pro-apoptotic activities and might be useful in the clinical treatment of BPH.
使君子已被用于治疗胃痛、便秘和消化问题等病症。本研究旨在评估使君子提取物对LNCaP人前列腺癌细胞系和睾酮诱导的良性前列腺增生(BPH)大鼠模型中治疗良性前列腺增生的疗效。用使君子加丙酸睾酮(TP)处理LNCaP细胞,并通过蛋白质免疫印迹法评估雄激素受体(AR)和前列腺特异性抗原(PSA)的表达水平。为诱导BPH,给大鼠每日皮下注射TP(3mg/kg),持续4周。治疗组大鼠在注射TP的同时口服使君子(150mg/kg)。体外研究表明,使君子处理可降低TP诱导的LNCaP细胞中AR和PSA表达的增加。在BPH模型大鼠中,使君子治疗后前列腺重量、血清睾酮、双氢睾酮(DHT)浓度和前列腺组织中2型5α-还原酶mRNA表达均显著降低。在使君子处理的大鼠中,TP诱导的前列腺增生以及增殖细胞核抗原(PCNA)和细胞周期蛋白D1的表达均显著减弱。此外,使君子通过上调BPH大鼠前列腺组织中半胱天冬酶-3和-9的活性以及降低B细胞淋巴瘤2(Bcl-2)/Bcl-2相关X蛋白(Bax)的比值来诱导细胞凋亡。进一步研究表明,使君子给药可降低TP诱导的AKT和糖原合酶激酶3β(GSK3β)的激活。因此,我们的研究结果表明,使君子通过抗增殖和促凋亡活性减轻大鼠的BPH状态,可能对BPH的临床治疗有用。