Antidepressant‑like efect of dehydrozingerone from Zingiber ofcinale by elevating monoamines in brain: in silico and in vivo studies

Moorkoth, Sudheer and Sai Prathyusha, N and Manandhar, Suman and Sankhe, Runali and Pai, Sreedhara Ranganath K and Kumar, Nitesh (2021) Antidepressant‑like efect of dehydrozingerone from Zingiber ofcinale by elevating monoamines in brain: in silico and in vivo studies. Pharmacological Reports, 73. pp. 1273-1286. ISSN 1734-1140

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Abstract

Background Dehydrozingerone (DHZ) is an active ingredient of Zingiber ofcinale and structural half analogue of curcumin. In the present study, DHZ was evaluated for monoamine oxidase (MAO) inhibitory activity in silico and antidepressant activity in vivo. Method The binding afnity of DHZ with MAO-A (PDB ID: 2Z5Y) was assessed using Schrodinger’s Maestro followed by free energy calculation, pharmacokinetic property prediction using Qikprop and Molecular dynamics simulation using Desmond. In vivo antidepressant activity of DHZ was evaluated on C57 BL/6 male mice using Escilatopram as the standard antidepressant. Open feld test (OFT), forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant efect of the drugs on days 1 and 7. Following the behavioural study, neurotransmitters (noradrenaline, dopamine and serotonin) were estimated using liquid chromatography–mass spectrometry. Results DHZ demonstrated a greater binding afnity for the MAO-A enzyme compared to moclobemide in silico. Immobility in TST and FST were signifcantly (p < 0.05) reduced in vivo with 100mg/kg DHZ as compared to respective controls. DHZ treatment was more efective 1 h post treatment compared to vehicle control. A signifcant increase in levels of neurotransmitters was observed in mice brain homogenate in response to DHZ treatment, reassuring its antidepressant-like potential. Conclusion DHZ demonstrated MAO-A inhibition in silico, and the increased neurotransmitter levels in the brain in vivo were associated with an antidepressant-like efect

Item Type: Article
Uncontrolled Keywords: Dehydrozingerone ; Depression ; Monoamine oxidase-A ; Neurotransmitter ; Molecular dynamics ; LCMS
Subjects: Pharmacy > MCOPS Manipal > Pharmaceutical Quality Assurance
Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Library
Date Deposited: 01 Feb 2022 10:49
Last Modified: 01 Feb 2022 10:49
URI: http://eprints.manipal.edu/id/eprint/158256

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