The hypothalamic–pituitary–adrenal (HPA) system plays an important role in stress response. Chronic stress is thought to induce neuronal damage and contribute to the pathogenesis of psychiatric disorders by causing dysfunction of the HPA system and promoting the production and release of glucocorticoids, including corticosterone and cortisol. Several clinical studies have demonstrated the efficacy of herbal medicines in treating psychiatric disorders; however, their effects on corticosterone-induced neuronal cell death remain unclear. Here, we used HT22 cells to evaluate the neuroprotective potential of herbal medicines used in neuropsychiatry against corticosterone-induced hippocampal neuronal cell death. Cell death was assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) reduction and Live/Dead assays. Hangekobokuto, Kamikihito, Saikokaryukotsuboreito, Kamishoyosan, and Yokukansan were supplied in the form of water-extracted dried powders. Exposure of HT22 cells to ≥ 100 μM corticosterone decreased MTT values. Exposure to 500 μM corticosterone alone reduced MTT values to 18%, while exposure to 10 μM Mifepristone (RU486)—a glucocorticoid receptor antagonist—restored values to 36%. Corticosterone-induced cell death was partially suppressed by treatment with RU486. At 100 μg/mL, Hangekobokuto significantly suppressed the decrease in MTT values (15–32%) and increase in the percentage of ethidium homodimer-1-positive dead cells caused by corticosterone exposure (78–36%), indicating an inhibitory effect on cell death. By contrast, Kamikihito, Saikokaryukotsuboreito, Kamishoyosan, and Yokukansan did not affect corticosterone-induced cell death. Therefore, our results suggest that Hangekobokuto may ameliorate the onset and progression of psychiatric disorders by suppressing neurological disorders associated with increased levels of glucocorticoids.

Graphical abstract

中文翻译：

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Hangekobokuto 对皮质酮诱导的 HT22 细胞死亡的细胞保护作用

下丘脑-垂体-肾上腺（HPA）系统在应激反应中发挥着重要作用。慢性压力被认为会引起神经元损伤，并通过引起 HPA 系统功能障碍并促进糖皮质激素（包括皮质酮和皮质醇）的产生和释放，从而导致精神疾病的发病机制。多项临床研究已证明草药在治疗精神疾病方面的功效；然而，它们对皮质酮诱导的神经元细胞死亡的影响仍不清楚。在这里，我们使用 HT22 细胞来评估神经精神病学中使用的草药对皮质酮诱导的海马神经元细胞死亡的神经保护潜力。使用 3-[4,5-二甲基噻唑-2-基]-2,5 二苯基溴化四唑 (MTT) 还原和活/死测定法评估细胞死亡。Hangekobokuto、Kamikihito、Saikokaryukotsuboreito、Kamishoyosan 和 Yokukansan 以水提干燥粉末的形式提供。HT22 细胞暴露于 ≥ 100 μM 皮质酮会降低 MTT 值。单独暴露于 500 μM 皮质酮可将 MTT 值降低至 18%，而暴露于 10 μM 米非司酮 (RU486)（一种糖皮质激素受体拮抗剂）可将 MTT 值恢复至 36%。RU486 治疗部分抑制了皮质酮诱导的细胞死亡。在 100 μg/mL 时，Hangekobokuto 显着抑制了由于皮质酮暴露引起的 MTT 值下降 (15-32%) 和乙锭同二聚体-1 阳性死细胞百分比的增加 (78-​​36%)，表明对细胞死亡。相比之下，Kamikihito、Saikokaryukotsuboreito、Kamishoyosan 和 Yokukansan 不影响皮质酮诱导的细胞死亡。因此，我们的结果表明，Hangekobokuto 可能通过抑制与糖皮质激素水平增加相关的神经系统疾病来改善精神疾病的发病和进展。

图形概要