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    Zanthoxylum alatum Attenuates Lipopolysaccharide-Induced Depressive-like Behavior in Mice Hippocampus

    Chandana Choudhury Barua1★, Beenita Saikia1, Xinguo Ren2, R. Elancheran3, Debesh Chandra Pathak4, Shantanu Tamuli5, Acheenta Gohain Barua6★ Corresponding author

    1. 1Departments of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University.
    2. 2Department of Psychiatry, Molecular Biology Research Building, University of Illinois, Chicago, IL, USA.
    3. 3Division of Life Science, Drug Discovery Lab, Institute of Advanced Study in Science and Technology, Guwahati, Assam, India.
    4. 4Veterinary Pathology.
    5. 5Veterinary Biochemistry and.
    6. 6Veterinary Public Health, College of Veterinary Science, Assam Agricultural University.

    CORRESPONDENCE

    Chandana Choudhury Barua

    Departments of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University.

    chanacin@gmail.com

    Received: 20-12-2017; Revised: 01-02-2018.

    Volume 14, Issue 59s · pp. S673–S682 · PUBLISHED 17 January 2019 · DOI: 10.4103/pm.pm_606_17

    View on Pharmacogn. Mag. original site ↗

    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- B (NFB), 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 NFB, 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 NFB, 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.

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      Barua, C. C., Saikia, B., Ren, X., Elancheran, R., Pathak, D. C., Tamuli, S., & Barua, A. G. (2019). Zanthoxylum alatum Attenuates Lipopolysaccharide-Induced Depressive-like Behavior in Mice Hippocampus. Pharmacognosy Magazine, 14(59s), S673–S682. https://doi.org/10.4103/pm.pm_606_17