Zanthoxylum alatum attenuates lipopolysaccharide-induced depressive-like behavior in mice hippocampus

Chandana Choudhury Barua; Beenita Saikia; Xinguo Ren; R Elancheran; Debesh Chandra Pathak; Shantanu Tamuli; Acheenta Gohain Barua

Articles

Abstract

Pharmacognosy Magazine,2018,14,59s,s673-682s.

DOI:10.4103/pm.pm_606_17

Published:January 2019

Type:Original Article

Authors:

Author(s) affiliations:

Chandana Choudhury Barua¹, Beenita Saikia¹, Xinguo Ren², R Elancheran³, Debesh Chandra Pathak⁴, Shantanu Tamuli⁵, Acheenta Gohain Barua⁶
¹ Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam, India
² Department of Psychiatry, Molecular Biology Research Building, University of Illinois, Chicago, IL, USA
³ Division of Life Science, Drug Discovery Lab, Institute of Advanced Study in Science and Technology, Guwahati, Assam, India
⁴ Department of Veterinary Pathology, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam, India
⁵ Department of Veterinary Biochemistry, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam, India
⁶ Department of Veterinary Public Health, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam, India

Abstract:

Background: Zanthoxylum alatum (ZA) is used ethnomedicinally for the treatment of various diseases. It is used as a nerve tonic in weak patients and in vertigo. Objective: The beneficial effect of hydroethanolic extract of ZA seeds (HEZA) on lipopolysaccharide (LPS)-induced depression-like behavior in mice was studied with its possible underlying mechanisms. Materials and Methods: HEZA (100 and 200 mg/kg, p.o.) and imipramine (10 mg/kg, i.p) were administered for 14 consecutive days, followed by LPS (0.83 mg/kg i.p) injection, 30 min posttreatment. Behavioral studies including the open field test, forced swimming test, tail suspension test and sucrose preference test were performed after 24 h of LPS administration. Levels of pro-oxidant markers (Lipid peroxidation (LPO), Nitric oxide (NO) and antioxidant enzyme viz. Glutathione (GSH), Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx) were estimated biochemically; Norepinephrine (NE), Dopamine (DA) and 5-hydroxytryptamine (5-HT) levels by high-performance liquid chromatography; nuclear factor- κB (NFκB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and caspase-3 mRNA expression using reverse transcription-polymerase chain reaction; the proteins of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB), in hippocampal tissue were evaluated by Western blot. Hesperidin, magnoflorine, melicopine, and sesamin were few phytoconstituents identified by liquid chromatography–electrospray ionization–tandem mass spectrometry studies. Results: Administration of LPS produced significant depression-like behavior by reducing the locomotor activity in open field test, increasing the immobility time in forced swim test and tail suspension test, increased LPO, NO, decreased GSH, SOD, CAT, GPx levels; lowered NE, DA and 5-HT level, upregulated NFκB, Nrf2 and Caspase-3 mRNA expression and downregulated BDNF, TrKB protein expression. Pretreatment with imipramine and HEZA reversed LPS-induced behavioral patterns, inhibited oxido-nitrosative stress, elevated antioxidant enzyme levels, and normalized the NE, DA, and 5-HT levels. The treatment also suppressed the mRNA expression of NFκB, Nrf2, and Caspase-3 gene with upregulation of BDNF protein expression, the molecular marker for depression. Conclusion: Antidepressant-like activity of HEZA is assumed to be mediated by antioxidant property, impending neuroinflammation, alteration of monoaminergic responses, and preventing BDNF depletion.