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Glycyrrhizae Radix suppresses lipopolysaccharide- and diazepam-induced nerve inflammation in the hippocampus, and contracts the duration of pentobarbital- induced loss of righting reflex in a mouse model

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Abstract

Nerve inflammation is linked to the development of various neurological disorders. This study aimed to examine whether Glycyrrhizae Radix effectively influences the duration of the pentobarbital-induced loss of righting reflex, which may increase in a mouse model of lipopolysaccharide (LPS)-induced nerve inflammation and diazepam-induced γ-aminobutyric acid receptor hypersensitivity. Furthermore, we examined the anti-inflammatory effects of Glycyrrhizae Radix extract on LPS-stimulated BV2 microglial cells, in vitro. Treatment with Glycyrrhizae Radix significantly decreased the duration of pentobarbital-induced loss of righting reflex in the mouse model. Furthermore, treatment with Glycyrrhizae Radix significantly attenuated the LPS-induced increases in interleukin-1β, interleukin-6, and tumor necrosis factor-alpha at the mRNA level, and it significantly reduced the number of ionized calcium-binding adapter molecule-1-positive cells in the hippocampal dentate gyrus 24 h after LPS treatment. Treatment with Glycyrrhizae Radix also suppressed the release of nitric oxide, interleukin-1β, interleukin-6, and tumor necrosis factor protein in culture supernatants of LPS-stimulated BV2 cells. In addition, glycyrrhizic acid and liquiritin, active ingredients of Glycyrrhizae Radix extract, reduced the duration of pentobarbital-induced loss of righting reflex. These findings suggest that Glycyrrhizae Radix, as well as its active ingredients, glycyrrhizic acid and liquiritin, may be effective therapeutic agents for the treatment of nerve inflammation-induced neurological disorders.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by JSPS KAKENHI Grant Number 20H01008.

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Authors and Affiliations

  1. Graduate School of Integrated Arts and Sciences, Kochi University, 185-1 Kohasu, Oko, Nankoku, Kochi, Japan

    Kei Kawada, Shumpei Morisawa, Motoki Nishida, Naohisa Tamura & Mitsuhiko Miyamura

  2. Department of Pharmacy, Kochi Medical School Hospital, 185-1 Kohasu, Oko-cho, Nankoku, Kochi, Japan

    Kei Kawada, Tomoaki Ishida, Kohei Jobu, Shumpei Morisawa, Motoki Nishida, Naohisa Tamura, Saburo Yoshioka & Mitsuhiko Miyamura

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  1. Kei Kawada
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  2. Tomoaki Ishida
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  6. Naohisa Tamura
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  8. Mitsuhiko Miyamura
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Contributions

KK: conceptualization, methodology, Investigation, writing—original draft, project administration, funding acquisition. TI: conceptualization, methodology, formal analysis, investigation, writing—review and editing. KJ: validation, investigation, resources, writing—review and editing. SM: investigation. TK: investigation. MN: investigation. SN: investigation. NT: investigation. SY: investigation, data curation. MM: resources, writing—review and editing, supervision.

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Correspondence to Kei Kawada.

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The authors have no competing interests to declare that are relevant to the content of this article.

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Animal experiments were approved by the Committee for the Care and Use of Laboratory Animals at Kochi University (approval no. O-0009, April 23, 2021).

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Kawada, K., Ishida, T., Jobu, K. et al. Glycyrrhizae Radix suppresses lipopolysaccharide- and diazepam-induced nerve inflammation in the hippocampus, and contracts the duration of pentobarbital- induced loss of righting reflex in a mouse model. J Nat Med 77, 561–571 (2023). https://doi.org/10.1007/s11418-023-01700-2

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  • DOI: https://doi.org/10.1007/s11418-023-01700-2

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