Transcriptional regulation of corticotrophin releasing factor gene by furocoumarins isolated from seeds of Psoralea corylifolia.
Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system plays a causal role in the development and course of depression. Clinically effective antidepressant drugs normalize the disturbed activity of the HPA axis by inhibition of corticotrophin releasing factor gene promoter activity. Furocoumarins from Psoralea corylifolia have been demonstrated to possess potent antidepressant properties. In order to ascertain whether these coumarin components directly regulate corticotrophin releasing factor (CRF) gene transcription, we studied their effect on CRF promoter activity using the luciferase reporter assay in Neuro-2A cells. CRF promoter was cloned into firefly luciferase reporter vector and co-transfected into Neuro-2A cells with Renilla luciferase plasmid as internal control. CRF promoter transcription activity was induced by forskolin. We found that one of the components of P. corylifolia, psoralidin, strongly inhibited forskolin-induced CRF promoter activity. We further confirmed that psoralidin suppressed CRF gene transcription by quantitative reverse transcription polymerase chain reaction. Hence, down-regulation of CRF gene transcription by psoralidin may be involved in the molecular mechanism underlying its potent antidepressant effect.
Chen
Yangchao
Y
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
Cheung
Yuen-Ting
YT
Kong
Ling-dong
LD
Ng
Tzi Bun
TB
Qiao
Chunfeng
C
Mo
Shi-fu
SF
Xu
Hong-xi
HX
Kung
Hsiang-fu
HF
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics*; D005473:Fluoxetine / Q000494:pharmacology; D011564:Furocoumarins / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D029907:Psoralea / Q000737:chemistry*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012639:Seeds / Q000737:chemistry; D013778:Tetrazolium Salts; D013844:Thiazoles
D018687:Antidepressive Agents, Second-Generation; D011564:Furocoumarins; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D005473:Fluoxetine; D005576:Colforsin; D003346:Corticotropin-Releasing Hormone; C022616:thiazolyl blue