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Synergistic antidepressant-like effect of ferulic acid in combination with piperine: involvement of monoaminergic system

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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.

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Acknowledgments

G.W. Li, L.N. Ruan, R.J. Chen and R.Y. Wang contributed equally to this work. This work was funded by the Natural Science Foundation of Ningbo (No. 2012A610256; 2014A610256), 2015 Zhejiang provincial Public Welfare Technology Application Research Plan (2015C33297), and Ministry of Science and Technology Spark Plan (2014GA701011) for G.W. Li.; The Natural Science Foundation of Changzhou (No. ZD2O1413) for Dr. W. Huang; The National Institute of General Medical Sciences (Reed - U54GM104942) for Dr. M. Reed. Zhejiang Province Extremely Key Subject Building Funding “Pharmacology and Biochemical Pharmaceutics 2008”, Latitudinal project of Wenzhou Medical University (No. 95012011) and Natural Science Foundation of Zhejiang Province (No. Y14H310034) for Professor J. C. Pan.

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Authors and Affiliations

  1. Ningbo college of Health Sciences, Ningbo, Zhejiang Province, 325600, China

    Gaowen Li

  2. Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, 325021, China

    Lina Ruan, Xupei Xie, Qizhi Yan, Ying Xu & Jianchun Pan

  3. Department of Pharmacy, The Second Affiliate Hospital, Wenzhou Medical University, Wenzhou, 325021, China

    Ruijie Chen

  4. Taizhou Institution for Food and Drug Control, Taizhou, 318000, China

    Renye Wang

  5. Pingyang Hospital of Traditional Chinese Medicine, Pingyang, Zhejiang Province, 325400, China

    Meixi Zhang & Lichao Chen

  6. Behavioral Neuroscience, Department of Psychology, West Virginia University, Morgantown, West Virginia, 26505, USA

    Miranda Reed

  7. Department of Neurosurgery and Neurology, Changzhou Second People’s Hospital, Changzhou, Jiangsu Province, 213003, China

    Wu Huang

  8. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, 14214, USA

    Ying Xu

  9. Department of Neurology, Lianyungang second people’s Hospital, Lianyungang, Jiangsu Province, 222023, China

    Jiechun Chen

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  1. Gaowen Li
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  2. Lina Ruan
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  3. Ruijie Chen
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  4. Renye Wang
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  5. Xupei Xie
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  6. Meixi Zhang
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  7. Lichao Chen
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  8. Qizhi Yan
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  9. Miranda Reed
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  10. Jiechun Chen
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  11. Ying Xu
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  12. Jianchun Pan
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  13. Wu Huang
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Correspondence to Jianchun Pan or Wu Huang.

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Li, G., Ruan, L., Chen, R. et al. Synergistic antidepressant-like effect of ferulic acid in combination with piperine: involvement of monoaminergic system. Metab Brain Dis 30, 1505–1514 (2015). https://doi.org/10.1007/s11011-015-9704-y

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  • DOI: https://doi.org/10.1007/s11011-015-9704-y

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