Zhang Zhe, Huang Yun-Fang, Zhao Wen-Wen, Sun Xiu-Rui, Han Hong-Cui, Wang Xue, Jing Zi-Qi, Ma Peng-Kai, Zhang Yu-Jie
School of Chinese Materia Medica, Bejing University of Chinese Medicine Beijing 102488, China.
School of Chinese Materia Medica, Bejing University of Chinese Medicine Beijing 102488, China Department of Pharmacy, Shangluo Central Hospital Shangluo 726000, China.
Zhongguo Zhong Yao Za Zhi. 2022 Jan;47(1):159-166. doi: 10.19540/j.cnki.cjcmm.20210802.402.
To explore the mechanism of Suanzaoren Decoction in the treatment of insomnia from endogenous bile acid regulation, the present study investigated the hepatoprotective effect of Suanzaoren Decoction and the molecular changes of bile acids in the serum, liver, and ileum of insomnia model mice and Suanzaoren Decoction treated mice. The insomnia model in mice was established by the sleep deprivation method. After Suanzaoren Decoction(48.96 mg·kg(-1)·d(-1)) intervention by gavage for 7 days, the related indicators, such as water consumption, food intake, body weight, aspartate aminotransferase(AST), alanine transaminase(ALT), and total bile acid(TBA) were detected, and the pathological changes of the liver and ileum were observed. The molecular levels and distribution of 23 bile acids in the serum, liver, and ileum were analyzed by UPLC-MS/MS combined with principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA). The results showed that Suanzaoren Decoction could improve the decreased water consumption and food intake, weight loss, and increased AST and ALT in the model group, and effectively reverse the injury and inflammation in the liver and ileum. The bile acids in the liver of the insomnia model mice were in the stage of decompensation, and the bile acids in the serum, liver, and ileum of the mice decreased or increased. Suanzaoren Decoction could regulate the anomaly of some bile acids back to normal. Seven bile acids including glycoursodeoxycholic acid(GUDCA), glycodesoxycholic acid(GDCA), tauro-α-MCA(T-α-MCA), α-MCA, taurodeoxycholate(TDCA), T-β-MCA, and LCA were screened out as the main discriminant components by PLS-DA. It is concluded that Suanzaoren Decoction possesses the hepatoprotective effect and bile acids could serve as the biochemical indicators to evaluate the drug efficacy in the treatment of abnormal liver functions caused by insomnia. The mechanism of Suanzao-ren Decoction in soothing the liver, resolving depression, tranquilizing the mind, and improving sleep may be related to the molecular regulation of bile acid signals.
为从内源性胆汁酸调节方面探讨酸枣仁汤治疗失眠的机制，本研究考察了酸枣仁汤对失眠模型小鼠及酸枣仁汤治疗小鼠血清、肝脏和回肠中胆汁酸的分子变化及肝脏保护作用。采用睡眠剥夺法建立小鼠失眠模型。以酸枣仁汤（48.96 mg·kg⁻¹·d⁻¹）灌胃干预7天后，检测小鼠的饮水量、进食量、体重、天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）及总胆汁酸（TBA）等相关指标，并观察肝脏和回肠的病理变化。采用超高效液相色谱-串联质谱（UPLC-MS/MS）结合主成分分析（PCA）和偏最小二乘判别分析（PLS-DA）分析血清、肝脏和回肠中23种胆汁酸的分子水平及分布情况。结果显示，酸枣仁汤可改善模型组小鼠饮水量减少、进食量减少、体重减轻以及AST和ALT升高的情况，并有效逆转肝脏和回肠的损伤及炎症。失眠模型小鼠肝脏中的胆汁酸处于失代偿阶段，小鼠血清、肝脏和回肠中的胆汁酸出现减少或增加的情况。酸枣仁汤可使部分胆汁酸异常调节恢复正常。通过PLS-DA筛选出甘氨熊去氧胆酸（GUDCA）、甘氨脱氧胆酸（GDCA）、牛磺-α-鼠胆酸（T-α-MCA）、α-鼠胆酸、牛磺脱氧胆酸盐（TDCA）、T-β-鼠胆酸和石胆酸（LCA）7种胆汁酸作为主要判别成分。结论：酸枣仁汤具有肝脏保护作用，胆汁酸可作为评估其治疗失眠所致肝功能异常疗效的生化指标。酸枣仁汤疏肝解郁、安神助眠的机制可能与胆汁酸信号的分子调节有关。
