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Metab Brain Dis. 2018 Apr;33(2):467-480. doi: 10.1007/s11011-017-0144-8. Epub 2017 Nov 3.

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.

Author information

1
Division of Pharmacology and Center of Excellence for Pharmaceutical Sciences, School of Pharmacy, North West University, Internal box 16, Potchefstroom, 2520, South Africa.
2
Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Deakin University, Locked Bag 20000, Geelong, 3220, Australia.
3
Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, P.O. Box 291, Geelong, 3220, Australia.
4
Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, 3052, Australia.
5
Department of Psychiatry, Level 1 North, Main Block, Royal Melbourne Hospital, University of Melbourne, Parkville, 3052, Australia.
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.
7
Division of Pharmacology and Center of Excellence for Pharmaceutical Sciences, School of Pharmacy, North West University, Internal box 16, Potchefstroom, 2520, South Africa. Brian.Harvey@nwu.ac.za.

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.

KEYWORDS:

Chromatographic fingerprinting; Ethnopharmacology; Inflammation; Mangosteen; Oxidative stress; Psychiatry

PMID:
29101602
DOI:
10.1007/s11011-017-0144-8

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