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ABSTRACT
Objectives: Depression is a common neuropsychiatric disorder. The available pharmacotherapy is ineffective for a substantial proportion of patients and has numerous side effects. Therefore, finding safer drugs for the management of depression is of paramount importance. The present study was aimed to identify the compound responsible for anti-depressant like effects of Allium cepa outer scale extract (ACE) and to elucidate its mechanism of action.
Methods:The anti-depressant compound from ACE was separated using bioactivity guided fractionation. Furthermore, mouse model of unpredictable chronic mild stress (UCMS) induced depressive behaviour was employed to investigate the anti-depressant like activity and potential mechanism of bioactive compound using behavioural tests (forced swim test (FST), sucrose preference test (SPT), open field test (OFT)) as well as by assessing brain oxidative stress, monoamine oxidase A and serotonin levels.
Results:ACE and its ethylacetate fraction (EF) showed marked anti-depressant like effects in mice in the FST model. Chromatographic and spectroscopic studies of EF lead to the isolation of quercetin and quercetin 4'-O-glucoside (QG). Of these, QG (20 mg/kg) treated animals showed activity similar to that shown by fluoxetine in mice using FST. Thus, QG was tested for anti-depressant like activity against UCMS induced depressive behaviour in mice. Treatment of UCMS- exposed mice with QG (20 mg/kg) improved UCMS induced behaviour anomalies and restored brain biochemical parameters (oxidative stress, MAO-A activity and serotonin levels).
Discussion:QG is responsible for anti-depressant like effects of ACE possibly via prevention of brain oxidative stress and restoring serotonin levels by inhibiting MAO-A activity.
Supplementary material
The HPLC chromatogram of ethylacetate fraction, and 1H and 13C NMR spectra and mass spectra of isolated compounds are available as supplementary material.
Acknowledgements
The authors are highly thankful to the Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India for providing all the necessary facilities to carry out this research.
Disclosure statement
No potential conflict of interest was reported by the authors.
Notes on contributors
Varinder Singh is working as Assistant Professor at Maharaja Agrasen School of Pharmacy, Maharaja Agrasen University, Baddi, Himachal Pradesh, India. He got his Ph.D. in Pharmacognosy from Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India. He is actively involved in exploring the wealth of natural medicine especially herbal drugs for the management of neurological disorders. He has been awarded with UGC-BSR fellowship from University Grants Commission, New Delhi, India (Government of India). Currently, he is performing research activities independently at Maharaja Agrasen University, Baddi, Himachal Pradesh.
Gargi Chauhan is an M.Pharm student at Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India. She is working on the isolation of bioactive compounds from medicinal plants.
Richa Shri is a professor of Pharmacognosy at the Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India. She studied from UIPS, Panjab University, Chandigarh, India. She strongly believes that nature has an answer to all human needs and ailments; we only have to understand what nature is saying. Her areas of research interest are biological and phytochemical evaluation of plants with neuroprotective, anti-anxiety and anti-depressant activities. Currently, she and her team are investigating the efficacy of the genus Allium in various neurodegenerative disorders.