Nobiletin, a flavone from shekwasha (Citrus depressa), alleviates hypertensive bladder response

抄録

Nobiletin, is a polymethoxy flavonoid abundantly present in citrus fuits, including shekwasha (citrus depressa) producd in southern parts of Japan such as Okinawa.This study aimed to clarify the effect of a nobiletin on urodynamic functions in anesthetized cystitis rat cystometry. Futhermore, to understand the mechanism of effect of nobiletine on urodynamic functions, we performed in vitro organ bath study and measured intracellular cAMP concentration on rat bladder strips.

　The effect of single oral administration of nobiletin mixture (50 mg/kg) was examined on urodynamic parameters in cystometrograms of anesthetized cystitis rats induced by cyclophosphamide. In organ bath study, rat urine bladder smooth muscle stirps were placed in organ baths containing 10 mL of an aerated Krebs-Henseteit solution, and contractions were recorded using isometric force displacement transducers. Following the acquisition of control 80 mM KCl response, acetylcholine (ACh) was added to the bath at 100 µM. Then, to investigate the effet of nobiletin on ACh-induced contraction, it was added at 1 mM and harvested bladder strips for measuring intracellular cAMP.

　Single oral administration of nobiletin in CYP-induced cystitis rat cystometry caused an increase in the micturition interval and voided volume and a significant decrease of micturition frequency during the intravesical infusion of saline. The nobiletin had little effect on the threshold pressure and basal pressure, but maximum micturition pressure was significantry decreased . Nobiletine significantly inhibited ACh-induced contraction on the rat bladder strips and significantrly increased intracellular cAMP concentration.

　Single oral administration of nobiletin alleviated significantly urodynamic symptoms in hyperactive rat bladder by prolonging the micturition interval and decreasing micturition frequency. Although the precise mechanism which nobiletin improved a hyperactive bladder response in CYP-induced cystitis rats remains to be clarified, the potency of increasing intracellular cAMP in the bladder smooth mascles may be partly contribute to the beneficial effect.

　Nobiletin improved significantly urodynamic symptoms in hyperactive rat bladders by decreasing the micturition frequency. Thus, the current results may support the clinical efficacy of nobiletin mixture in the treatment of lower urinary tract symptoms accompanying overactive bladder.