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1.
J Nat Med ; 77(3): 561-571, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37115471

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-1ß, 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-1ß, 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.


Subject(s)
Drugs, Chinese Herbal , Glycyrrhiza , Mice , Animals , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Glycyrrhizic Acid/pharmacology , Pentobarbital/pharmacology , Pentobarbital/therapeutic use , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Diazepam/therapeutic use , Reflex, Righting , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Hippocampus/metabolism , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Drugs, Chinese Herbal/pharmacology
2.
J Nat Med ; 76(3): 634-644, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35257304

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.


Subject(s)
Delirium , Lipopolysaccharides , Animals , Delirium/metabolism , Diazepam/metabolism , Diazepam/pharmacology , Diazepam/therapeutic use , Drugs, Chinese Herbal , Glycyrrhizic Acid/pharmacology , Hippocampus , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Mice , NF-kappa B/metabolism , Neuroinflammatory Diseases , Pentobarbital/metabolism , Pentobarbital/pharmacology , Pentobarbital/therapeutic use , Reflex, Righting , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
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