Correlation between the metabolic profile of Nelumbo Seed, a component of Seishinrenshiin, and its inhibitory activity on bladder smooth muscle contraction

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.