title: Lipopolysaccharide induced anxiety- and depressive-like behaviour in mice are prevented by chronic pre-treatment of esculetin.
abstract: Inflammation and oxidative stress are involved in the pathophysiology of anxiety and depression. Esculetin (ESC), a coumarin derived potent antioxidant, also possessing anti-inflammatory and neuroprotective activity. This study investigated the effect of ESC in lipopolysaccharide (LPS)-induced anxiety- and depressive-like behaviour in mice. ESC (25 and 50mg/kg, p.o.) was administered daily for 14 days, and challenged with saline or LPS (0.83mg/kg; i.p.) on the 15th day. Behavioural paradigms such as elevated plus maze (EPM), open field test (OFT), forced swim test (FST) and tail suspension test (TST) were employed to assess anxiety- and depressive-like behaviour in mice post-LPS injection. Hippocampal cytokines, MDA and GSH level, and plasma corticosterone (CORT) were measured. ESC pre-treatment significantly (P<0.05) attenuated LPS-induced anxiety-like behaviour by modulating EPM and OFT parameters. Moreover, LPS-induced increase in immobility time in FST and TST were also prevented significantly (P<0.05) by ESC (50mg/kg). ESC pre-treatment ameliorated LPS-induced neuroinflammation by attenuating brain IL-1β, IL-6, TNF-α level, and oxidative stress as well as plasma CORT level. In conclusion, the results suggest that ESC prevented LPS-induced anxiety- and depressive-like behaviour which may be governed by inhibition of cytokine production, oxidative stress and plasma CORT level. The results support the potential usefulness of ESC in the treatment of psychiatric disorders associated with inflammation and oxidative stress.
authors.affiliation: Laboratory of Neuroscience, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India. Electronic address: niperkunj@gmail.com.
authors.forename: Kunjbihari
authors.initials: K
authors.lastname: Sulakhiya
authors.affiliation: Laboratory of Neuroscience, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India.
authors.forename: Gohil Pratik
authors.initials: GP
authors.lastname: Keshavlal
authors.affiliation: Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India.
authors.forename: Babul B
authors.initials: BB
authors.lastname: Bezbaruah
authors.affiliation: Laboratory of Neuroscience, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India.
authors.forename: Shubham
authors.initials: S
authors.lastname: Dwivedi
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India.
authors.forename: Satendra Singh
authors.initials: SS
authors.lastname: Gurjar
authors.affiliation: Laboratory of Neuroscience, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Munde
authors.affiliation: Laboratory of Neuroscience, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Jangra
authors.affiliation: Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India.
authors.forename: Mangala
authors.initials: M
authors.lastname: Lahkar
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India.
authors.forename: Ranadeep
authors.initials: R
authors.lastname: Gogoi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014468:Umbelliferones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014468:Umbelliferones; C007628:esculetin; D003345:Corticosterone
keywords: Anxiety; Depression; Esculetin; Lipopolysaccharide; Neuroinflammation; Oxidative stress