Antidepressant-like effect of dehydrozingerone from Zingiber officinale by elevating monoamines in brain: in silico and in vivo studies

Abstract

Background Dehydrozingerone (DHZ) is an active ingredient of Zingiber officinale 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 affinity 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 field test (OFT), forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant effect 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 affinity for the MAO-A enzyme compared to moclobemide in silico. Immobility in TST and FST were significantly (p < 0.05) reduced in vivo with 100mg/kg DHZ as compared to respective controls. DHZ treatment was more effective 1 h post treatment compared to vehicle control. A significant 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 effect.

Discovery of Novel Boron-Containing N-Substituted Oseltamivir Derivatives as Anti-Influenza A Virus Agents for Overcoming N1-H274Y Oseltamivir-Resistant

“…Then, 2c was drawn using ChemDraw professional software, imported to Maestro and then optimized using the LigPrep module. LigPrep performed the 3D structure conversion from 2D with accurate chiralities and an OPLS force field was applied to generate stable conformer with minimum potential energy [ 43 ]. The crystal structures of N1 (H5N1, PDB code: 2HU0) and N1-H274Y (H5N1-H274Y, PDB code: 3CL0) were retrieved from molecular dynamics (MD) simulations using Amber14 software as previously described [ 28 ].…”

Dehydrozingerone Alleviates Hyperalgesia, Oxidative Stress and Inflammatory Factors in Complete Freund’s Adjuvant-Induced Arthritic Rats

“…The dose of DHZ chosen in this experiment was according to previous studies. 9 , 10 The animals were treated daily for 28 days, and body weight gain of the animals was routinely recorded.…”

“…Previous studies have reported several pharmacological properties of DHZ, including anti-inflammatory, antioxidant, antiobesity, anticancer, neuroprotective, tyrosinase inhibitory, antidepressant and antifungal effects. [9][10][11][12] However, despite the numerous reports of the therapeutic effects of DHZ, there are no reports on whether DHZ possesses therapeutic efficacy on RA. As such, the present study evaluated the therapeutic effects of DHZ in rat models of CFA-induced arthritis.…”

Antifungal Activity of Ginger Rhizome Extract against Fusarium solani

“…Results indicate that ginger contains monoterpenoids, sesquiterpenoids, phenolic compounds, and its derivatives, aldehydes, ketones, alcohols, esters, which provide a broad antimicrobial spectrum against different microorganisms and make it an interesting alternative to synthetic antimicrobials [13,14]. For example, 6-gingerol inhibits the proliferation of human cervical cancer cells and induces their apoptosis [15]. Recent studies have shown that both ginger extract and ginger essential oil have antifungal activities against plant pathogens, such as Fusarium oxysporum and Colletotrichum falcatum [16,17].…”