2. Academic Validation
  3. In Vitro and In Vivo Characterization of the Alkaloid Nuciferine

In Vitro and In Vivo Characterization of the Alkaloid Nuciferine

  • PLoS One. 2016 Mar 10;11(3):e0150602. doi: 10.1371/journal.pone.0150602.
Martilias S Farrell 1,  John D McCorvy 1,  Xi-Ping Huang 1 2,  Daniel J Urban 1,  Kate L White 1,  Patrick M Giguere 1,  Allison K Doak 3,  Alison I Bernstein 4,  Kristen A Stout 4,  Su Mi Park 5,  Ramona M Rodriguiz 5,  Bradley W Gray 6,  William S Hyatt 6,  Andrew P Norwood 6,  Kevin A Webster 7,  Brenda M Gannon 6,  Gary W Miller 4,  Joseph H Porter 7,  Brian K Shoichet 3,  William E Fantegrossi 6,  William C Wetsel 5,  Bryan L Roth 1 8 9 10 11 12 2
Affiliations

Affiliations

  • 1 Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
  • 2 National Institute of Mental Health Psychoactive Drug Screening Program, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
  • 3 Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America.
  • 4 Department of Environmental Health, Rollins School of Public Health and Center for Neurodegenerative Diseases, Emory University, Atlanta, Georgia, United States of America.
  • 5 Departments of Psychiatry and Behavioral Sciences, Cell Biology, and Neurobiology, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical Center, Durham, North Carolina, United States of America.
  • 6 Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
  • 7 Department of Psychology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
  • 8 Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
  • 9 Program in Neuroscience, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
  • 10 Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
  • 11 Carolina Institute for Developmental Disabilities, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
  • 12 Division of Chemical Biology and Medicinal Chemistry, School of Pharmacy, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
PMID: 26963248 DOI: 10.1371/journal.pone.0150602
Abstract

Rationale: The sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. Nuciferine, an alkaloid component of Nelumbo nucifera and Nymphaea caerulea, had a predicted molecular profile similar to antipsychotic compounds. Our study characterizes nuciferine using in vitro and in vivo pharmacological assays.

Methods: Nuciferine was first characterized in silico using the similarity ensemble approach, and was followed by further characterization and validation using the Psychoactive Drug Screening Program of the National Institute of Mental Health. Nuciferine was then tested in vivo in the head-twitch response, pre-pulse inhibition, hyperlocomotor activity, and drug discrimination paradigms.

Results: Nuciferine shares a receptor profile similar to aripiprazole-like antipsychotic drugs. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the Dopamine Transporter. In rodent models relevant to antipsychotic drug action, nuciferine blocked head-twitch responses and discriminative stimulus effects of a 5-HT2A agonist, substituted for clozapine discriminative stimulus, enhanced amphetamine induced locomotor activity, inhibited phencyclidine (PCP)-induced locomotor activity, and rescued PCP-induced disruption of prepulse inhibition without induction of catalepsy.

Conclusions: The molecular profile of nuciferine was similar but not identical to that shared with several approved antipsychotic drugs suggesting that nuciferine has atypical antipsychotic-like actions.

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