title: Gomisin N ameliorates lipopolysaccharide-induced depressive-like behaviors by attenuating inflammation in the hypothalamic paraventricular nucleus and central nucleus of the amygdala in mice.
abstract: Emotional impairments such as depressive symptoms often develop in patients with sustained and systemic immune activation. The objective of this study is to investigate the effect of gomisin N, a dibenzocyclooctadiene lignan isolated from the dried fruits of Schisandra chinensis (Turcz.) Baill., which exhibited inhibitory effects of the bacterial endotoxin lipopolysaccharide (LPS)-induced NO production in a screening assay, on inflammation-induced depressive symptoms. We examined the effects of gomisin N on inflammation induced by LPS in murine microglial BV-2 cells and on LPS-induced behavioral changes in mice. Gomisin N inhibited LPS-induced expression of mRNAs for inflammation-related genes (inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α) in BV-2 cells. Administration of gomisin N attenuated LPS-induced expression of mRNAs for inflammation-related genes, increases in the number of c-Fos immunopositive cells in the hypothalamus and amygdala, depressive-like behavior in the forced swim test and exploratory behavior deficits 24 h after LPS administration in mice. These results suggest that gomisin N might ameliorate LPS-induced depressive-like behaviors through inhibition of inflammatory responses and neural activation in the hypothalamus and amygdala.
authors.affiliation: Laboratory of Functional Biomolecules and Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan. Electronic address: r-araki@pharm.setsunan.ac.jp.
authors.forename: Ryota
authors.initials: R
authors.lastname: Araki
authors.affiliation: Laboratory of Functional Biomolecules and Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hiraki
authors.affiliation: Laboratory of Functional Biomolecules and Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Nishida
authors.affiliation: Laboratory of Functional Biomolecules and Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Inatomi
authors.affiliation: Laboratory of Functional Biomolecules and Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan. Electronic address: yabe@pharm.setsunan.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yabe
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D066274:Central Amygdaloid Nucleus / Q000187:drug effects / Q000378:metabolism*; D034242:Cyclooctanes / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000139:chemically induced / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011083:Polycyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D032141:Schisandra
chemical_list: D000893:Anti-Inflammatory Agents; D034242:Cyclooctanes; D018836:Inflammation Mediators; D017705:Lignans; D008070:Lipopolysaccharides; D010936:Plant Extracts; D011083:Polycyclic Compounds; C015499:schizandrin B
keywords: Amygdala; Depressive-like behavior; Gomisin N; Hypothalamus; Lipopolysaccharide