title: Honokiol abrogates chronic restraint stress-induced cognitive impairment and depressive-like behaviour by blocking endoplasmic reticulum stress in the hippocampus of mice.
abstract: The primary objective of our study is to investigate the neuroprotective efficacy of honokiol and imipramine against restraint stress (RS)-induced cognitive impairment and depressive-like behaviour in mice. We examined whether the neuroprotective activity of honokiol and imipramine mediates through the inhibition of endoplasmic reticulum stress. Adult Swiss albino mice were restrained for 6h/day for 28 days. Honokiol (3 and 10mg/kg) and Imipramine (10 and 30mg/kg) were administered for last 7 days to the different groups. Cognitive function was assessed by Morris water maze and novel object recognition test. Forced swimming test and tail suspension test were performed to evaluate the restraint stress-induced depressive-like behaviour. Proinflammatory cytokines, brain-derived neurotrophic factor, and ER stress markers i.e. 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) were quantified in the hippocampus. We observed cognitive impairment and depressive-like behaviour in RS-exposed animals. Honokiol (10mg/kg) treated group depicted marked reduction in cognitive impairment and depressive-like behaviour. However, imipramine (10 and 30mg/kg) prevented the depressive-like behaviour but failed to prevent RS-induced cognitive impairment. Moreover, proinflammatory cytokines, GRP78 and CHOP were elevated in the hippocampus of stressed mice as compared to unstressed mice. Honokiol (10mg/kg) significantly prevented the RS-induced elevated levels of proinflammatory cytokines and endoplasmic reticulum stress markers. Our results clearly suggest the beneficial potential of honokiol in restraint stress through inhibition of proinflammatory cytokines and endoplasmic reticulum stress. Honokiol could be an intriguing therapeutic approach in endoplasmic reticulum stress related neuro-pathophysiological conditions.
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam 781032, India; Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Jangra
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam 781032, India; Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India.
authors.forename: Shubham
authors.initials: S
authors.lastname: Dwivedi
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam 781032, India; Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India.
authors.forename: Chandra Shaker
authors.initials: CS
authors.lastname: Sriram
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India; Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India.
authors.forename: Satendra Singh
authors.initials: SS
authors.lastname: Gurjar
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam 781032, India; Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India.
authors.forename: Mohit
authors.initials: M
authors.lastname: Kwatra
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam 781032, India; Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India.
authors.forename: Kunjbihari
authors.initials: K
authors.lastname: Sulakhiya
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam 781022, India; Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India.
authors.forename: Chandana C
authors.initials: CC
authors.lastname: Baruah
authors.affiliation: Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, Assam 781032, India; Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam 781022, India; Department of Pharmacology, Gauhati Medical College, Guwahati, Assam 781032, India. Electronic address: dr.mlahkar@gmail.com.
authors.forename: Mangala
authors.initials: M
authors.lastname: Lahkar
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D016207:Cytokines / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007099:Imipramine / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D012149:Restraint, Physical / Q000523:psychology; D013315:Stress, Psychological / Q000150:complications*; D051742:Transcription Factor CHOP / Q000235:genetics; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007099:Imipramine; D017705:Lignans; D051742:Transcription Factor CHOP; C497250:Ddit3 protein, mouse; C000717248:Hspa5 protein, mouse; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: Cognitive impairment; Depressive-like behaviour; Endoplasmic reticulum stress; Honokiol; Imipramine; Restraint stress