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Garcinia mangostana Linn displays antidepressant-like and pro-cognitive effects in a genetic animal model of depression: a bio-behavioral study in the Flinders Sensitive Line rat

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Abstract

There is abundant evidence for both disorganized redox balance and cognitive deficits in major depressive disorder (MDD). Garcinia mangostana Linn (GM) has anti-oxidant activity. We studied the antidepressant-like and pro-cognitive effects of raw GM rind in Flinders Sensitive Line (FSL) rats, a genetic model of depression, following acute and chronic treatment compared to a reference antidepressant, imipramine (IMI). The chemical composition of the GM extract was analysed for levels of α- and γ-mangostin. The acute dose-dependent effects of GM (50, 150 and 200 mg/kg po), IMI (20 mg/kg po) and vehicle were determined in the forced swim test (FST) in FSL rats, versus Flinders Resistant Line (FRL) control rats. Locomotor testing was conducted using the open field test (OFT). Using the most effective dose above coupled with behavioral testing in the FST and cognitive assessment in the novel object recognition test (nORT), a fixed dose 14-day treatment study of GM was performed and compared to IMI- (20 mg/kg/day) and vehicle-treated animals. Chronic treated animals were also assessed with respect to frontal cortex and hippocampal monoamine levels and accumulation of malondialdehyde. FSL rats showed significant cognitive deficits and depressive-like behavior, with disordered cortico-hippocampal 5-hydroxyindole acetic acid (5-HIAA) and noradrenaline (NA), as well as elevated hippocampal lipid peroxidation. Acute and chronic IMI treatment evoked pronounced antidepressant-like effects. Raw GM extract contained 117 mg/g and 11 mg/g α- and γ-mangostin, respectively, with acute GM demonstrating antidepressant-like effects at 50 mg/kg/day. Chronic GM (50 mg/kg/d) displayed significant antidepressant- and pro-cognitive effects, while demonstrating parity with IMI. Both behavioral and monoamine assessments suggest a more prominent serotonergic action for GM as opposed to a noradrenergic action for IMI, while both IMI and GM reversed hippocampal lipid peroxidation in FSL animals. Concluding, FSL rats present with cognitive deficits and depressive-like behaviors that are reversed by acute and chronic GM treatment, similar to that of IMI.

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Acknowledgements

The authors would like to thank Hylton Bunting and Antoinette Fick for their assistance in the breeding and welfare of the animals. The authors would also like to thank Dr Dewet Wolmarans for assistance with analyzing the nORT data, Dr Makhotso Lekhooa for valuable insights into the writing of the paper, and Trent Ashton (Deakin University, Australia) for assisting with the chromatographic fingerprinting of GM. We also acknowledge Walter Dreyer and Francois Viljoen for their assistance during the ELISA and HPLC analyses, respectively.

Sources of funding

The authors declare that this work has been funded by the South African National Research Foundation (BHH; grant number 77323). The grant-holder acknowledges that opinions, findings and conclusions or recommendations expressed in any publication generated by NRF supported research are those of the authors, and that the NRF accepts no liability whatsoever in this regard. This funder had no other role in the study. MB is supported by a NHMRC Senior Principal Research Fellowship 1,059,660.

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Authors and Affiliations

  1. Division of Pharmacology and Center of Excellence for Pharmaceutical Sciences, School of Pharmacy, North West University, Internal box 16, Potchefstroom, 2520, South Africa

    Inge Oberholzer, Marisa Möller & Brian H. Harvey

  2. Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Deakin University, Locked Bag 20000, Geelong, 3220, Australia

    Brendan Holland

  3. Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, P.O. Box 291, Geelong, 3220, Australia

    Olivia M. Dean & Michael Berk

  4. Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, 3052, Australia

    Olivia M. Dean

  5. Department of Psychiatry, Level 1 North, Main Block, Royal Melbourne Hospital, University of Melbourne, Parkville, 3052, Australia

    Olivia M. Dean

  6. Orygen, The National Centre of Excellence in Youth Mental Health, the Department of Psychiatry, and the Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia

    Michael Berk

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The authors declare that over the past three years, Brian Harvey has participated in advisory boards and received honoraria from Servier®, and has received research funding from Servier® and Lundbeck®. The authors declare that, except for income from the primary employer and research funding to BHH from the above-mentioned organizations and agencies, no financial support or compensation has been received from any individual or corporate entity over the past three years for research or professional services, and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.

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Oberholzer, I., Möller, M., Holland, B. et al. Garcinia mangostana Linn displays antidepressant-like and pro-cognitive effects in a genetic animal model of depression: a bio-behavioral study in the Flinders Sensitive Line rat. Metab Brain Dis 33, 467–480 (2018). https://doi.org/10.1007/s11011-017-0144-8

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