Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin Health Industry Park, Jinghai District, Tianjin, 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formula, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin Health Industry Park, Jinghai District, Tianjin, 301617, China.
Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin Health Industry Park, Jinghai District, Tianjin, 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
J Ethnopharmacol. 2021 Mar 25;268:113666. doi: 10.1016/j.jep.2020.113666. Epub 2020 Dec 7.
ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis Franch (CCF), also known as Huang Lian in China, is a traditional Chinese medicine that commonly used for more than 2000 years. Clinically, CCF often used as anti-inflammatory, immune regulation and other effects. It has been reported that the decoction containing CCF can be used for the treatment of benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS). AIM OF THE STUDY: This research aims to investigate the effect of CCF on inhibition of BPH development in vivo and in vitro, and further identify the active compound (s) and the possible mechanism involved in BPH-related bladder dysfunction. MATERIALS AND METHODS: Oestrodial/testosterone-induced BPH rat model was established as the in vivo model. The prostate index (PI) was calculated, the pathogenesis was analyzed and the micturition parameters were determined in the shamed-operated, BPH model and BPH + CCF groups after 4-week administration. The tension in detrusor strips was then assessed upon KCl or ACh stimulation with or without incubation of CCF or active compounds. To further investigate the signaling involved, rat detrusor cells were cultured as the in vitro models, the instantaneous calcium influx was measured and the ROCK-1 expression was detected. RESULTS: Increased PI value and the aggravated prostatic pathology were observed with voiding dysfunction in BPH rats, which were significantly blocked by oral CCF taken. ACh or KCl-induced contractile responses in detrusor strips were significantly inhibited and the micturition parameters were improved when incubation with CCF or its active compounds such as berberine. Both CCF and berberine suppressed the cellular calcium influx and ROCK-1 expression upon ACh stimulation, demonstrating that berberine was one of the active compounds that contributed to CCF-improved micturition symptoms and function. CONCLUSIONS: Taken together, our findings give evidence that CCF and its active compound berberine inhibited BPH and bladder dysfunction via Ca and ROCK signaling, supporting their clinical use for BPH and BPH-related LUTS treatment.
药用植物学相关性：黄连（Coptis chinensis Franch，简称 CCF）是中国传统医学中一种使用了两千多年的草药。临床上，CCF 常被用作抗炎、免疫调节等。有报道称，含有 CCF 的汤剂可用于治疗良性前列腺增生（BPH）或下尿路症状（LUTS）。
研究目的：本研究旨在探讨 CCF 对体内和体外 BPH 发展的抑制作用，并进一步鉴定与 BPH 相关膀胱功能障碍相关的活性化合物（s）和可能的作用机制。
材料和方法：建立了雌激素/睾丸酮诱导的 BPH 大鼠模型作为体内模型。在 4 周给药后，通过计算前列腺指数（PI）、分析发病机制和测定排尿参数，对假手术、BPH 模型和 BPH+CCF 组进行评估。然后，在没有或有 CCF 或活性化合物孵育的情况下，通过 KCl 或 ACh 刺激评估逼尿肌条的张力。为了进一步研究涉及的信号通路，将大鼠逼尿肌细胞培养为体外模型，测量瞬时钙内流并检测 ROCK-1 表达。
结果：BPH 大鼠出现排尿功能障碍，表现为 PI 值升高和前列腺病理加重，这些变化均被口服 CCF 显著阻断。当用 CCF 或其活性化合物如小檗碱孵育时，ACh 或 KCl 诱导的逼尿肌条收缩反应明显受到抑制，排尿参数得到改善。CCF 和小檗碱均抑制了 ACh 刺激时的细胞钙内流和 ROCK-1 表达，表明小檗碱是 CCF 改善排尿症状和功能的活性化合物之一。
结论：综上所述，我们的研究结果表明，CCF 及其活性化合物小檗碱通过 Ca 和 ROCK 信号通路抑制 BPH 和膀胱功能障碍，支持其在 BPH 和 BPH 相关 LUTS 治疗中的临床应用。
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