Cerebral MAO Activity Is Not Altered by a Novel Herbal Antidepressant Treatment

  • Ravid DoronEmail author
  • Ziv Versano
  • Or Burstein
  • Motty Franko
  • Alon Shamir
  • Roni Toledano
  • Assaf Handelsman
  • Moshe Rehavi


Inhibition of monoamine oxidase (MAO)-A/B can ameliorate depressive- and anxiety-related symptoms via increase of monoamine extracellular levels. However, such inhibition can also instigate hypertensive response following exposure to dietary tyramine (i.e., “the cheese effect”). Novel herbal treatment (NHT) is an herbal formula that has been demonstrated to reduce depressive- and anxiety-like symptoms in pre-clinical studies. The aim of the current study was to examine whether the therapeutic potential of NHT is underlain by inhibition of MAO-A/B and whether NHT poses a risk for tyramine hyper-potentiation. Unpredictable chronic mild stress (UCMS)–exposed mice and naïve mice were treated for 3 weeks with NHT (30 mg/kg; i.p.), the selective serotonin reuptake inhibitor (SSRI) escitalopram (15 mg/kg; i.p.), or saline. Subsequently, MAO-A/B activities in the hypothalamus, striatum, and prefrontal cortex (PFC) were assessed. Exposure to UCMS led to significant increases in both MAO-A and MAO-B activities in the hypothalamus (p < 0.001) and in the PFC (p < 0.01 for MAO-A; p < 0.001 for MAO-B). Neither NHT nor escitalopram had any notable effects. Treatment with NHT was supported as safe in terms of risk for inducing a hypertensive response. The antidepressant- and anxiolytic-like effects of NHT are mediated via pathways other than MAO-A/B inhibition.


Monoamine oxidase A/B (MAO-A/B) Unpredictable chronic mild stress (UCMS) Depression Novel herbal treatment (NHT) Escitalopram 



The authors would like to thank Nadav Kately for inventing and developing the NHT formula, Yafit Hirshler for her support in the realization of the manuscript, and Dr. Fong-pin Liang from KPC for his support in gathering data regarding the herbal compounds of NHT used in this study.

Compliance with Ethical Standards

Ethical Approval

All procedures were performed in accordance with the ethical standards of The Academic College Tel Aviv Yaffo Committee for Animal Care and Use, and The Guide for the Care and Use of Laboratory Animals of the National Institutes of Health guidelines were followed.

Conflict of Interest

Ravid Doron has an approved patent relating to the herbal treatment for anxiety disorders (patent no. 9,320,772, USA). Other than that, all authors assert that none has any commercial or financial involvements that might present an appearance of a conflict of interest in connection with the submitted manuscript.

Supplementary material

12031_2019_1366_MOESM1_ESM.pdf (59 kb)
Supplementary Figure 1 (PDF 58 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department Of Education and PsychologyThe Open University of IsraelRa’ananaIsrael
  2. 2.School Of Behavioral ScienceThe Academic College Tel Aviv YaffoTel AvivIsrael
  3. 3.Department of Physiology and Pharmacology, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  4. 4.The Dr. Miriam and Sheldon G. Adelson Chair and Center for the Biology of Addictive DiseasesTel Aviv UniversityTel AvivIsrael
  5. 5.Faculty of MedicineTechnion – Israel Institute of TechnologyHaifaIsrael
  6. 6.Mazor Mental Health CenterAkkoIsrael

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