title: St. John's Wort increases brain serotonin synthesis by inhibiting hepatic tryptophan 2, 3 dioxygenase activity and its gene expression in stressed rats.
abstract: We aimed to investigate the effects of herbal St. John's Wort (SJW) on transcriptional regulation of hepatic tryptophan 2, 3 - dioxygenase (TDO) enzyme activity and brain regional serotonin (5-HT) levels in rats exposed to forced swim test (FST). TDO mRNA expression was quantified using real-time reverse transcription polymerase chain (RT-PCR) reaction and brain regional indoleamines were determined by high performance liquid chromatography coupled to fluorescence detector. Behavioral analysis shows significant reduction in immobility time in SJW (500mg/kg/ml) administered rats. It was found that pretreatment of SJW to rats did not prevent stress-induced elevation in plasma corticosterone levels however it increases serotonin synthesis by virtue of inhibiting hepatic TDO enzyme activity and its gene expression, ascertaining the notion that there exists an inverse relationship between hepatic TDO enzyme activity and brain 5-HT. The drug also decreases serotonin turnover in all the brain areas (hypothalamus, hippocampus amygdala) in stressed rats endorsing its monoamine oxidase inhibition property. Inhibition of TDO enzyme activity and its gene expression by the drug provides new insights for the development of therapeutic interventions for stress related mental illnesses.
authors.affiliation: Clinical Biochemistry and Psychopharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi.
authors.forename: Samina
authors.initials: S
authors.lastname: Bano
authors.affiliation: Clinical Biochemistry and Psychopharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi.
authors.forename: Iffat
authors.initials: I
authors.lastname: Ara
authors.forename: Kausar
authors.initials: K
authors.lastname: Saboohi
authors.affiliation: Department of Pathology and Microbiology, The Aga Khan University Hospital, Karachi, Pakistan.
authors.forename: Tariq
authors.initials: T
authors.lastname: Moattar
authors.affiliation: Department of Biological and Biomedical Sciences, The Aga Khan University Hospital, Karachi, Pakistan.
authors.forename: Bushra
authors.initials: B
authors.lastname: Chaoudhry
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020902:Hypericum; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000096:biosynthesis*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000523:psychology; D014158:Transcription, Genetic / Q000187:drug effects; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D012333:RNA, Messenger; D012701:Serotonin; D014366:Tryptophan Oxygenase; D003345:Corticosterone