Journal of Natural Medicines ( IF 2.5 ) Pub Date : 2022-03-08 , DOI: 10.1007/s11418-022-01612-7 Kei Kawada 1, 2 , Tomoaki Ishida 2 , Kohei Jobu 2 , Shumpei Morisawa 1, 2 , Tetsushi Kawazoe 1, 2 , Motoki Nishida 1, 2 , Satomi Nishimura 1, 2 , Naohisa Tamura 1, 2 , Saburo Yoshioka 2 , Mitsuhiko Miyamura 1, 2
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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
中文翻译：
Yokukansan 抑制小鼠海马中的神经炎症，并减少戊巴比妥诱导的脂多糖和地西泮介导的翻正反射丧失的持续时间
神经炎症与低活跃性谵妄的发展有关，这会导致不良的临床结果。尚未确定有效对抗低活性 sur 的药物。Yokukansan 具有抗神经炎症作用，使其可能有效对抗低活性谵妄。本研究旨在检查 Yokukansan 对小鼠模型中戊巴比妥诱导的翻正反射持续时间丧失的影响，该持续时间因脂多糖 (LPS) 诱导的神经炎症和地西泮诱导的 γ-氨基丁酸受体刺激而延长。还研究了 Yokukansan 中的活性成分及其对海马的抗神经炎症作用。此外，我们检测了 Yokukansan 对 LPS 刺激的 BV2 细胞（一种小鼠小胶质细胞系）的体外抗炎作用。研究结果表明，用 Yokukansan 治疗通过减弱 LPS 诱导的海马白细胞介素 6 和肿瘤坏死因子 α 水平的增加，显着缩短了戊巴比妥诱导的翻正反射丧失的持续时间。此外，在 LPS 给药 24 小时后，用 Yokukansan 治疗显着减少了海马齿状回中离子化钙结合衔接分子 1 阳性细胞的数量。此外，Yokukansan 中的活性成分甘草酸可部分缩短戊巴比妥引起的翻正反射丧失的持续时间。Yokukansan 治疗还抑制了 LPS 刺激的 BV2 细胞中诱导型一氧化氮、白细胞介素 6 和肿瘤坏死因子 mRNA 的表达。因此，
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