Harada Kazuo, Fukuda Yuki, Ohkubo Takahiro, Sugaya Kimio, Osaki Yukihiko
Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita, Osaka, 565-0871, Japan.
Central R&D Laboratory, KOBAYASHI Pharmaceutical Co., Ltd, 1-30-3 Toyokawa, Ibaraki, Osaka, 567-0057, Japan.
J Nat Med. 2025 May;79(3):556-567. doi: 10.1007/s11418-025-01889-4. Epub 2025 Mar 19.
Seishinrenshiin (SRI), a Kampo formula, is often used for frequent urination. Nelumbo Seed, a crude-drug component of SRI was reported to inhibit bladder smooth muscle contraction using excised rat bladder tissues. However, the active ingredients of Nelumbo Seed have not yet been identified. In this study, we investigated the active ingredients of Nelumbo Seed that inhibit bladder smooth muscle contraction. We obtained liquid chromatography/mass spectrometry profiles of extracts prepared from five types of Nelumbo Seed materials from different production areas and evaluated their inhibitory effects on excised rat bladder smooth muscle contraction. Analysis of these data using orthogonal projections to latent structures revealed neferine (Nef) as the compound with the highest variable influence on projection. Among the Nelumbo Seed materials processed using different methods, the Nef content was the highest in 'Sekirenshi', when embryo and pericarp were not removed at all. We determined the effects of administering Nelumbo Seed extracts with different Nef content on frequent-urination model rats. The Nef content in rat plasma was the highest when the Sekirenshi extract was administered, but Nef was not detected when seed embryos were removed. In this model, administration of the Nelumbo Seed extract improved the maximum bladder contraction pressure and bladder contraction interval, albeit not significantly. In particular, Sekirenshi tended to reduce the maximum bladder contraction pressure compared to other Nelumbo Seed. Our results indicate that although Nef in Nelumbo Seed does not clearly improve frequent urination, it might contribute to the improvement of urination disorder.
精神苓心饮（SRI）是一种汉方制剂，常用于治疗尿频。据报道，SRI的一种生药成分莲子可使用切除的大鼠膀胱组织抑制膀胱平滑肌收缩。然而，莲子的活性成分尚未确定。在本研究中，我们调查了莲子中抑制膀胱平滑肌收缩的活性成分。我们获得了来自不同产地的五种莲子材料提取物的液相色谱/质谱图，并评估了它们对切除的大鼠膀胱平滑肌收缩的抑制作用。使用正交投影到潜在结构对这些数据进行分析，发现甲基莲心碱（Nef）是对投影影响最大的化合物。在使用不同方法加工的莲子材料中，“石莲子”中Nef含量最高，因为其完全未去除胚和果皮。我们测定了给不同Nef含量的莲子提取物对尿频模型大鼠的影响。给予石莲子提取物时，大鼠血浆中Nef含量最高，但去除种子胚后未检测到Nef。在该模型中，给予莲子提取物可改善最大膀胱收缩压和膀胱收缩间隔，尽管效果不显著。特别是，与其他莲子相比，石莲子倾向于降低最大膀胱收缩压。我们的结果表明，虽然莲子中的Nef不能明显改善尿频，但它可能有助于改善排尿障碍。
