title: Ferulic acid-induced anti-depression and prokinetics similar to Chaihu-Shugan-San via polypharmacology.
abstract: Selective serotonin reuptake inhibitors (SSRIs), one of popular antidepressants as "one-compound-one-target" paradigm, cannot but discontinue because of inhibiting gut movement. Traditional Chinese medicine (TCM) Chaihu-Sugan-San (CSS) can simultaneously exert anti-depression and prokinetics. From this thread, we aimed to find a new antidepressant with polypharmacological mechanisms. In vivo antidepressive and prokinetic comparisons between CSS and its absorbed compound ferulic acid (FA) were made. And FA's action mechanisms involved in monoaminergic systems, HPA axis and gastrointestinal peptide ghrelin was then studied in forced swimming test (FST) of rat. Lastly, the jejunal contraction activity evoked by FA was measured in vitro. Compared with vehicle, FA reduced immobility time, increased locomotor activity, accelerated gastric emptying and intestinal transit similar to CSS whose absorbable component FA was identified in hippocampus and jejunum. FA's prokinetics in vivo was further supported by its jejunal contraction in vitro. FA-induced anti-immobility was prevented by pretreated with PCPA, WAY-100635, ketanserin, sulpiride, SCH233390, haloperidol and yohimbine, respectively. CRH, ACTH and 5-HT were significantly decreased, but ghrelin was apparently increased compared with vehicle. In summary, FA induced anti-depression and prokinetics similar to CSS via inhibiting serotonin, norepinephrine and dopamine reuptakes, regulating HPA axis, increasing ghrelin and stimulating jejunal contraction simultaneously.
authors.affiliation: Western Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Ying-jin
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
authors.forename: Xin-jiang
authors.initials: XJ
authors.lastname: Qiu
authors.forename: Ping
authors.initials: P
authors.lastname: Ren
authors.forename: Li-chen
authors.initials: LC
authors.lastname: Gao
authors.forename: Hong-hao
authors.initials: HH
authors.lastname: Zhou
authors.forename: Hui-yun
authors.initials: HY
authors.lastname: Zhang
authors.forename: Ming-Qi
authors.initials: MQ
authors.lastname: Qiao
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003373:Coumaric Acids / Q000032:analysis / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D054439:Ghrelin / Q000378:metabolism; D007537:Isometric Contraction / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D009043:Motor Activity / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D019338:Polypharmacy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D015306:Biogenic Monoamines; D003373:Coumaric Acids; D054439:Ghrelin; D010936:Plant Extracts; C497000:chaihu-shugan-san; D005473:Fluoxetine; D012701:Serotonin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C004999:ferulic acid