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.

Possible Involvement of the IL-6/JAK2/STAT3 Pathway in the Hypothalamus in Depressive-Like Behavior of Rats Exposed to Chronic Mild Stress

“…Actually, STAT3 is activated through the phosphorylation of tyrosine, which was not assessed in our research. Lipopolysaccharide, a bacterial endotoxin, can induce depressive-like behavior [59]. Hosoi et al [60] found that i.p.…”

Standardized Extract of Atractylodis Rhizoma Alba and Fructus Schisandrae Ameliorates Coughing and Increases Expectoration of Phlegm

“…Atractylodis Rhizoma Alba was reported to inhibit inducible NO synthase [22] and inflammatory cytokines through mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) [23,24]. Individual constituents of Fructus Schisandrae, schisandrin A, schisandrin, and gomisin N were reported to display anti-inflammatory effects [25][26][27]. Therefore, anti-inflammatory activity from CKD-497 could be expected, and in the current study, the production of NO and inflammatory cytokines (IL-8, IL-12, IL-13, TNF-α, and TGF-β1) was suppressed in LPS-stimulated macrophages.…”

Schisandra chinensis Fructus and Its Active Ingredients as Promising Resources for the Treatment of Neurological Diseases

“…As Araki et al reported, gomisin N ameliorated LPS-induced inflammation in mice and BV2 cells. The research demonstrated that an elevation of the inflammatory markers induced by LPS was inhibited by gomisin N treatment [ 52 ].…”