Identification of oxytocin receptor activating chemical components from traditional Japanese medicine   全文下載

Identification of oxytocin receptor activating chemical components from traditional Japanese medicine

"Oxytocin (Oxt) is known to regulate social communication, stress and body weight. The activation of Oxt receptors(OTR) has clinical potential to abate stress disorders and metabolic syndrome. Kamikihito (KKT) is a traditional Japanesemedicine used to treat psychological stress-related disorders. We investigated the effects of KKT, its ingredientsand chemical components on Oxt neurons and OTR. C-Fos expression was examined after oral and peripheral administrationof KKT in rats. Electrophysiological change of Oxt neurons and Oxt release upon application of KKT weremeasured in rat brain slice. The direct effect of KKT, its ingredients and its chemical components were examined bycytosolic Ca2þ([Ca2þ]i) measurement in Oxt neurons and OTR-expressing HEK293 cells. Both intraperitoneal and oraladministration of KKT in rats induced c-Fos expression in neurons of the paraventricular nucleus (PVN) including Oxtneurons. Application of KKT induced activation of Oxt neurons and Oxt release. KKT increased [Ca2þ]i in OTRexpressingHEK293 cells, and failed to activate with OTR antagonist. KKT-induced PVN Oxt neuron activation was alsoattenuated by OTR antagonist. Seven chemical components (rutin, ursolic acid, (Z )-butylidenephtalide, p-cymene,senkunolide, [6]-shogaol, [8]-shogaol) of three ingredients (Zizyphi Fructus, Angelicae Acutilobae Radix, ZingiberisRhizoma) from KKT had potential to activate OTR. KKT can directly activate PVN Oxt neurons by interacting with OTR.The interaction of seven chemical components from KKT may contribute to activate OTR. Effect of KKT on Oxt neuronsand OTR may contribute to the treatment of Oxt related disorders."