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Erschienen in: Journal of Natural Medicines 3/2022

08.03.2022 | Original Paper

Yokukansan suppresses neuroinflammation in the hippocampus of mice and decreases the duration of lipopolysaccharide- and diazepam-mediated loss of righting reflex induced by pentobarbital

verfasst von: Kei Kawada, Tomoaki Ishida, Kohei Jobu, Shumpei Morisawa, Tetsushi Kawazoe, Motoki Nishida, Satomi Nishimura, Naohisa Tamura, Saburo Yoshioka, Mitsuhiko Miyamura

Erschienen in: Journal of Natural Medicines | Ausgabe 3/2022

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Abstract

Neuroinflammation is associated with the development of hypoactive delirium, which results in poor clinical outcomes. Drugs effective against hypoactive sur have not yet been established. Yokukansan has an anti-neuroinflammatory effect, making it potentially effective against hypoactive delirium. This study aimed to examine the effect of Yokukansan on the pentobarbital-induced loss of righting reflex duration extended with lipopolysaccharide (LPS)-induced neuroinflammation and diazepam-induced gamma-aminobutyric acid receptor stimulation in a mouse model. The active ingredients in Yokukansan and its anti-neuroinflammatory effect on the hippocampus were also investigated. Furthermore, we examined the in vitro anti-inflammatory effects of Yokukansan on LPS-stimulated BV2 cells, a murine microglial cell line. Findings revealed that treatment with Yokukansan significantly decreased the duration of pentobarbital-induced loss of righting reflex by attenuating the LPS-induced increase in interleukin-6 and tumor necrosis factor-alpha levels in the hippocampus. Moreover, treatment with Yokukansan significantly decreased the number of ionized calcium-binding adapter molecule-1-positive cells in the hippocampal dentate gyrus after 24 h of LPS administration. In addition, glycyrrhizic acid, an active ingredient in Yokukansan, partially decreased the duration of pentobarbital-induced loss of righting reflex. Treatment with Yokukansan also suppressed the expression of inducible nitric oxide, interleukin-6, and tumor necrosis factor mRNA in LPS-stimulated BV2 cells. Thus, these findings suggest that Yokukansan and glycyrrhizic acid may be effective therapeutic agents for treating neuroinflammation-induced hypoactive delirium.

Graphical abstract

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Metadaten
Titel
Yokukansan suppresses neuroinflammation in the hippocampus of mice and decreases the duration of lipopolysaccharide- and diazepam-mediated loss of righting reflex induced by pentobarbital
verfasst von
Kei Kawada
Tomoaki Ishida
Kohei Jobu
Shumpei Morisawa
Tetsushi Kawazoe
Motoki Nishida
Satomi Nishimura
Naohisa Tamura
Saburo Yoshioka
Mitsuhiko Miyamura
Publikationsdatum
08.03.2022
Verlag
Springer Nature Singapore
Erschienen in
Journal of Natural Medicines / Ausgabe 3/2022
Print ISSN: 1340-3443
Elektronische ISSN: 1861-0293
DOI
https://doi.org/10.1007/s11418-022-01612-7

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