Identification of BKca channel activation effect of Kushen extract containing Kurarinone to ease urinary incontinence or overactive bladder

Abstract

The large‐conductance Ca2+‐activated K+ channel (or BKCa channel) requires membrane depolarization or increased intracellular Ca2+ for its activation. This channel makes one of the most effective ways to generate membrane hyperpolarization and regulates several key physiological processes. In the bladder, BKCa channel evokes the relaxation of urinary bladder smooth muscle and thus represents a therapeutic target for urinary incontinence (UI) or overactive bladder (OAB). In our previous study, we reported that kurarinone, a prenylated flavanone from Sophora flavescens, potently activates BKCa channel and established its therapeutic potential for treating OAB (Lee et al., Mol Pharmacol. 90:140, 2016). Subsequently, we identified five more flavonoids from Kushen, the dry root of S. flavescens. including kuraridinol, a prenylated chalcone, significantly potentiating BKCa channel activity (Lee et al., Biol Pharm Bull. 41:1295, 2018). In this study, we analyzed the components of Kushen extracts isolated with differential ethanol concentrations and tested their efficacy for BKCa channel activation. We found that the potentiation effect of various extracts for BKCa channel correlates well with the concentration of kurainone in the extracts. In addition, the Kushen extracts potently relaxed acetylcholine‐induced contraction of rat bladder smooth muscle and thus decreased the micturition frequency of rats with overactive bladder symptoms. Our results strongly support the idea that the Kushen extract containing kurarinone as the main ingredient can be utilized as nutraceutical or functional food against lower urinary tract symptom such as UI or OAB.Support or Funding InformationThis work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry (IPET) through Agri‐Bio industry Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (317070‐4)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.