Anxiolytic-like effects of hochuekkito in lipopolysaccharide-treated mice involve interleukin-6 inhibition.
Anxiolytic-like effects of hochuekkito in lipopolysaccharide-treated mice involve interleukin-6 inhibition.
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DOI：
10.3389/fphar.2022.890048
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发表时间：
2022
影响因子：
5.6
通讯作者：
Sendo, Toshiaki
中科院分区：
文献类型：
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作者：
Ushio, Soichiro;Wada, Yudai;Nakamura, Mizuki;Matsumoto, Daiki;Hoshika, Kota;Shiromizu, Shoya;Iwata, Naohiro;Esumi, Satoru;Kajizono, Makoto;Kitamura, Yoshihisa;Sendo, Toshiaki
Hochuekkito（HET）是一种汉方药，用于治疗术后和疾病后的全身不适和动力下降。已知HET调节免疫和调节炎症。然而，HET对炎症诱导的中枢神经系统疾病的确切机制和作用尚不清楚。本研究旨在探讨HET对炎症诱导的焦虑样行为的影响以及脂多糖（LPS）诱导的焦虑样行为的机制。用LPS（300 μg/kg，腹膜内）（一种细菌内毒素）处理癌症研究所小鼠以诱导全身炎症。在LPS处理之前，每天一次向小鼠施用HET（1.0g/kg，口服），持续2周。注射LPS后24 h，采用光暗箱实验和洞板实验观察HET对焦虑样行为的影响。注射LPS后2、5和24 h采集血清样本，测定血清中白细胞介素-6（IL-6）水平。采用人和小鼠巨噬细胞（分别为THP-1和RAW264.7细胞）研究HET对LPS诱导的IL-6分泌的影响。HET的重复给药可预防LPS处理小鼠的焦虑样行为，并降低血清IL-6水平。HET显著抑制LPS诱导的RAW264.7和THP-1细胞IL-6分泌。类似地，HET的化学成分之一的Escherin抑制LPS诱导的焦虑样行为。我们的研究表明，HET改善LPS诱导的焦虑样行为，并抑制IL-6的释放在体内和体外。因此，我们推测HET可能对炎症诱导的焦虑样行为有用。
Hochuekkito (HET) is a Kampo medicine used to treat postoperative and post-illness general malaise and decreased motivation. HET is known to regulate immunity and modulate inflammation. However, the precise mechanism and effects of HET on inflammation-induced central nervous system disorders remain unclear. This study aimed to assess the effect of HET on inflammation-induced anxiety-like behavior and the mechanism underlying anxiety-like behavior induced by lipopolysaccharide (LPS). Institute of Cancer Research mice were treated with LPS (300 μg/kg, intraperitoneally), a bacterial endotoxin, to induce systemic inflammation. The mice were administered HET (1.0 g/kg, orally) once a day for 2 weeks before LPS treatment. The light-dark box test and the hole-board test were performed 24 h after the LPS injection to evaluate the effects of HET on anxiety-like behaviors. Serum samples were obtained at 2, 5, and 24 h after LPS injection, and interleukin-6 (IL-6) levels in serum were measured. Human and mouse macrophage cells (THP-1 and RAW264.7 cells, respectively) were used to investigate the effect of HET on LPS-induced IL-6 secretion. The repeated administration of HET prevented anxiety-like behavior and decreased serum IL-6 levels in LPS-treated mice. HET significantly suppressed LPS-induced IL-6 secretion in RAW264.7 and THP-1 cells. Similarly, glycyrrhizin, one of the chemical constituents of HET, suppressed LPS-induced anxiety-like behaviors. Our study revealed that HET ameliorated LPS-induced anxiety-like behavior and inhibited IL-6 release in vivo and in vitro. Therefore, we postulate that HET may be useful against inflammation-induced anxiety-like behavior.
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