Uliginosin B, a Natural Phloroglucinol, Increases Hippocampal GSH, MCP-1 and IL-10 Levels in Mice

• Published in: Revista brasileira de farmacognosia 2023-12, Vol.33 (6), p.1274-1286
• Main Authors: Marangon, Caroline Guerra, Rojas, Camila Schafer, Michelsen, Marina Zaneti, Sakamoto, Satchie, Jacques, Carlos Eduardo Diaz, von Poser, Gilsane Lino, Regla Vargas, Carmen, Rates, Stela Maris Kuze
• Format: Article
• Language: English
• Subjects: Medicine; Original Article; Pharmacy
• ISSN: 1981-528X; 1981-528X
• DOI: 10.1007/s43450-023-00459-7

The activation of immuno-inflammatory pathways and oxidative/nitrosative stress results in behavioral, neurochemical, and neuroendocrine abnormalities such as those observed in depressive disorders. Uliginosin B, a natural dimeric acylphloroglucinol derivative, exhibits antidepressant-like effect in rodent models of depression, but its mode of action is still unclear. Therefore, the aim of this study was to investigate the effect of uliginosin B on hippocampal stress oxidative and inflammation markers in mice submitted to an immune challenge. Male CF1 mice were exposed to a stressful stimulus (5 min forced swimming) plus LPS from E. coli (450 µg/kg, i.p .) and then orally treated with uliginosin B 15 mg/kg, imipramine 20 mg/kg or vehicle 10 ml/kg. The animals were evaluated in the open field (6 and 24 h after immune challenging) and tail suspension test (24 h after immune challenging). The hippocampal levels of stress oxidative (sulfhydryl, catalase, glutathione reduced), thiobarbituric acid-reactive species and inflammatory markers (IL-6, IL-10, IL-12p70, MCP-1, IFN-γ, TNF-α) were measured. As expected, the administration of LPS preceded by a forced swimming session triggered sickness and depression-like behaviors in the open field and tail suspension test, respectively. Neither uliginosin B nor imipramine reduced the sickness behavior score. However, both drugs showed a partial protective effect against the depressive-like effect of LPS in the tail suspension test. Noteworthy, uliginosin B enhanced glutathione reduced, MCP-1 and IL-10 hippocampal levels. In conclusion, this study suggests that immuno-inflammatory and antioxidant pathways might play a role in the antidepressant-like effect of uliginosin B. Graphical Abstract