Erigeron linifolius attenuates lipopolysachharide-induced depressive-like behavior in mice by impeding neuroinflammation, oxido-nitrosative stress, and upregulation of tropomyosin receptor kinase B-derived neurotrophic factor and monoaminergic pathway in

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Pharmacognosy Magazine ,2019,15,62,92-103.
Published:April 2019
Type:Original Article
Authors:
Author(s) affiliations:

Chandana Choudhury Barua1, Kunjbihari Sulakhiya2, Prakash Haloi1, Lipika Buragohain1, Beenita Saikia1, Iswar Chandra Barua1, Debesh Chandra Pathak3, Shantanu Tamuli4, R Elancheran5, Xinquo Ren6
1Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam, India
2NeuroPharmacology Research Lab (NPRL) Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, India
3Department of Pathology, College of Veterinary Science, Guwahati, Assam, India
4Department of Animal Biochemistry, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam, India
5Drug Discovery Lab, Life Science Division, Institute of Advanced Study in Science and Technology, Guwahati, Assam, India
6Department of Psychiatry, Molecular Biology Research Building, University of Illinois, Chicago, Illinois, USA

Abstract:

Background: Immuno-inflammatory, oxido-nitrosative stress, brain-derived neurotrophic factor-tropomyosin receptor kinase (BDNF-TrkB), and monoaminergic pathways involve in the pathophysiology of depression. Erigeron linifolius (EL) possesses antioxidant, anticonvulsant, antitumor, and hypoglycemic activities. Objective: To investigate the effect of EL hydroalcoholic extract (ELHA) against lipopolysachharide (LPS)-induced depressive-like behavior and neurochemical alterations in mice. Materials and Methods: Mice were pretreated with vehicle, imipramine (10 mg/kg, intraperitoneally [i. p.]), and ELHA (100 and 200 mg/kg, per oral) for 14 days, and depressive-like behavior was induced by LPS (0.83 mg/kg, i. p.). Depressive-like behavior in mice was evaluated by open-field test, forced swimming test (FST), and tail suspension test (TST). Cytokines (tumor necrosis factor-alpha [TNF-α], interleukin-1β [IL-1β], IL-6, and IL-10), BDNF, monoamines (noradrenaline [NA], dopamine, 5-hydroxy), and oxido-nitrosative stress parameters (lipid peroxidation [LPO], glutathione [GSH], GSH peroxidase [GPx], catalase [CAT], superoxide dismutase [SOD], nitric oxide) were measured in the hippocampus (HC). Hippocampal caspase-3, nuclear factor-kappa B phosphor 65 (NF-κB p65), nuclear-related factor 2 (Nrf2), and TrkB and BDNF levels were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting. Results: Liquid chromatography-electrospray ionization-mass spectroscopy (MS)/MS analysis revealed the presence of ambrosin, friedelin, flavone, scopoletin, and luteolin in ELHA. ELHA showed significant antidepressant-like effect by decreasing the immobility time in FST and TST in LPS-challenged mice. Moreover, ELHA significantly attenuated TNF-α, IL-1β, IL-6, and LPO levels in LPS-challenged mice, whereas LPS-induced decrease in hippocampal IL-10, BDNF, GSH, GPx, CAT, SOD, and monoamine levels was also restored significantly by ELHA. RT-PCR and immunobloting results showed that ELHA significantly attenuated the upregulation of Caspase-3, NF-κB, p65, and Nrf2 and downregulation of TrkB and BDNF levels in the HC of LPS-challenged mice. Conclusion: The findings demonstrated antidepressant-like action of ELHA which could be due to the inhibition of neuroinflammation, oxido-nitrosative stress, and upregulation of TrkB-BDNF and monoaminergic pathways in the HC.

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