Zhou Heng-Pu, Su Jie, Wei Ke-Jian, Wu Su-Xiang, Yu Jing-Jing, Yu Yi-Kang, Niu Zhuang-Wei, Jin Xiao-Hu, Yan Mei-Qiu, Chen Su-Hong, Lyu Gui-Yuan
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Chin J Integr Med. 2025 Jun;31(6):490-498. doi: 10.1007/s11655-025-3925-7. Epub 2025 Apr 15.
To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia.
Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry.
DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01).
DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA receptors expressions and GA/GABA ratio.
探讨铁皮石斛提取物（DOE）对失眠的治疗作用及潜在机制。
将42只雄性Sprague-Dawley大鼠随机分为6组（每组n = 7）：正常对照组、模型对照组、褪黑素（MT，40 mg/kg）组及3个剂量的DOE组（0.25、0.50和1.00 g/kg）。将大鼠置于强光（10,000勒克斯）和高噪声（>80分贝）环境（每天12小时）中饲养16周以诱导失眠，从第10周开始至第16周，相应地对大鼠给予MT和DOE。采用戊巴比妥钠诱导的睡眠实验、蔗糖偏好实验和自主活动实验等行为学测试来评估大鼠睡眠和情绪的变化。检测大鼠的血压、血液黏度、血糖和尿酸等代谢相关指标。采用苏木精-伊红染色和尼氏染色评估大鼠脑海马1区（CA1）的病理变化。此外，采用酶联免疫吸附测定法检测γ-氨基丁酸（GABA）、谷氨酸（GA）、5-羟色胺（5-HT）和白细胞介素-6（IL-6）等睡眠相关因子。最后，使用聚合酶链反应（PCR）芯片筛选DOE潜在的改善睡眠的受体，并通过定量PCR和免疫组织化学验证结果。
DOE显著改善了大鼠的睡眠和情绪，延长了戊巴比妥钠诱导的睡眠时间，提高了蔗糖偏好指数，并减少了自主活动次数（P<0.05或P<0.01）。DOE对代谢异常也有良好作用，显著降低了甘油三酯、血糖、血压和血液黏度指标（P<0.05或P<0.01）。DOE显著增加了海马中GABA的含量，降低了GA/GABA比值和IL-6水平（P<0.05或P<0.01）。此外，DOE改善了海马细胞排列紊乱和尼氏体减少等病理变化。通过PCR芯片筛选出7个差异基因，并选择GABA受体（Gabra5、Gabra6、Gabrq）进行验证。结果显示DOE可上调它们的表达（P<0.05或P<0.01）。
DOE在改善失眠方面显示出显著潜力，可能是通过调节GABA受体表达和GA/GABA比值来实现。
