title: Synergistic antidepressant-like effect of ferulic acid in combination with piperine: involvement of monoaminergic system.
abstract: The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects.
authors.affiliation: Ningbo college of Health Sciences, Ningbo, Zhejiang Province, 325600, China.
authors.forename: Gaowen
authors.initials: G
authors.lastname: Li
authors.affiliation: Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325021, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Ruan
authors.affiliation: Department of Pharmacy, The Second Affiliate Hospital, Wenzhou Medical University, Wenzhou, 325021, China.
authors.forename: Ruijie
authors.initials: R
authors.lastname: Chen
authors.affiliation: Taizhou Institution for Food and Drug Control, Taizhou, 318000, China.
authors.forename: Renye
authors.initials: R
authors.lastname: Wang
authors.affiliation: Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325021, China.
authors.forename: Xupei
authors.initials: X
authors.lastname: Xie
authors.affiliation: Pingyang Hospital of Traditional Chinese Medicine, Pingyang, Zhejiang Province, 325400, China.
authors.forename: Meixi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Pingyang Hospital of Traditional Chinese Medicine, Pingyang, Zhejiang Province, 325400, China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Chen
authors.affiliation: Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325021, China.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Behavioral Neuroscience, Department of Psychology, West Virginia University, Morgantown, West Virginia, 26505, USA.
authors.forename: Miranda
authors.initials: M
authors.lastname: Reed
authors.affiliation: Department of Neurology, Lianyungang second people's Hospital, Lianyungang, Jiangsu Province, 222023, China.
authors.forename: Jiechun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325021, China.|Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, 14214, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325021, China. wenzhoupan2003@163.com.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Neurosurgery and Neurology, Changzhou Second People's Hospital, Changzhou, Jiangsu Province, 213003, China. wuhuang213003@163.com.
authors.forename: Wu
authors.initials: W
authors.lastname: Huang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D052117:Benzodioxoles / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism*; D001682:Biological Availability; D001923:Brain Chemistry / Q000187:drug effects; D003373:Coumaric Acids / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D004357:Drug Synergism; D019417:Hindlimb Suspension / Q000523:psychology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008995:Monoamine Oxidase / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D013550:Swimming / Q000523:psychology
chemical_list: D000470:Alkaloids; D000928:Antidepressive Agents; D052117:Benzodioxoles; D015306:Biogenic Monoamines; D003373:Coumaric Acids; D018377:Neurotransmitter Agents; D010880:Piperidines; D053284:Polyunsaturated Alkamides; C004999:ferulic acid; D008995:Monoamine Oxidase; C008922:piperine
keywords: Depression; Ferulic acid; MAO; Monoamines; Piperine