Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-Shi, Chiba, 274-8555, Japan.
Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan.
J Nat Med. 2024 Jan;78(1):255-265. doi: 10.1007/s11418-023-01766-y. Epub 2023 Nov 28.
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.
下丘脑-垂体-肾上腺 (HPA) 系统在应激反应中发挥重要作用。慢性应激被认为通过引起 HPA 系统功能障碍和促进皮质酮等糖皮质激素的产生和释放，导致神经元损伤，并促进精神疾病的发病机制。几项临床研究表明，草药在治疗精神疾病方面具有疗效；然而，它们对皮质酮诱导的神经元细胞死亡的影响尚不清楚。在这里，我们使用 HT22 细胞评估了几种用于神经精神疾病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]-2,5-二苯基四氮唑溴盐 (MTT) 还原和 Live/Dead 测定法评估细胞死亡。给予 HT22 细胞水提取物干燥粉末形式的柴胡加龙骨牡蛎汤、加味逍遥散、芍药甘草汤、归脾汤和六君子汤。暴露于≥100 μM 皮质酮会降低 MTT 值。单独暴露于 500 μM 皮质酮将 MTT 值降低至 18%，而单独暴露于 10 μM 米非司酮（RU486）-一种糖皮质激素受体拮抗剂-将值恢复至 36%。皮质酮诱导的细胞死亡部分被 RU486 抑制。在 100μg/mL 时，柴胡加龙骨牡蛎汤显著抑制 MTT 值的降低（15-32%）和暴露于皮质酮引起的 ethidium homodimer-1 阳性死细胞百分比的增加（78-36%），表明对细胞死亡具有抑制作用。相比之下，加味逍遥散、芍药甘草汤、归脾汤和六君子汤对皮质酮诱导的细胞死亡没有影响。因此，我们的结果表明，柴胡加龙骨牡蛎汤可能通过抑制与皮质酮水平升高相关的神经紊乱来改善精神疾病的发作和进展。
