Research Studio of Traditional Chinese Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian, China.
Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, Fujian, China.
J Ethnopharmacol. 2023 Aug 10;312:116446. doi: 10.1016/j.jep.2023.116446. Epub 2023 Apr 3.
Shuxie Compound (SX) combines the composition and efficacy of Suanzaoren decoction and Huanglian Wendan decoction. It can soothe the liver, regulate the qi, nourish the blood and calm the mind. It is used in the clinical treatment of sleep disorder with liver stagnation. Modern studies have proved that circadian rhythm disorder (CRD) can cause sleep deprivation and liver damage, which can be effectively ameliorated by traditional Chinese medicine to soothe the liver stagnation. However, the mechanism of SX is unclear.
This study was designed to demonstrate the impact of SX on CRD in vivo, and confirm the molecular mechanisms of SX in vitro.
The quality of SX and drug-containing serum was controlled by UPLC-Q-TOF/MS, which were used in vivo and in vitro experiments, respectively. In vivo, a light deprivation mouse model was used. In vitro, a stable knockdown Bmal1 cell line was used to explore SX mechanism.
Low-dose SX (SXL) could restore (1) circadian activity pattern, (2) 24-h basal metabolic pattern, (3) liver injury, and (4) Endoplasmic reticulum (ER) stress in CRD mice. CRD decreased the liver Bmal1 protein at ZT15, which was reversed by SXL treatment. Besides, SXL decreased the mRNA expression of Grp78/ATF4/Chop and the protein expression of ATF4/Chop at ZT11. In vitro experiments, SX reduced the protein expression of thapsigargin (tg)-induced p-eIF2α/ATF4 pathway and increase the viability of AML12 cells by increasing the expression of Bmal1 protein.
SXL relieved CRD-induced ER stress and improve cell viability by up-regulating the expression of Bmal1 protein in the liver and then inhibiting the protein expression of p-eIF2α/ATF4.
舒心复方（SX）结合了酸枣仁汤和黄连温胆汤的成分和功效。它可以疏肝理气、养血安神。临床上用于治疗肝郁型睡眠障碍。现代研究证明，昼夜节律紊乱（CRD）可导致睡眠剥夺和肝损伤，而疏肝解郁的中药可有效改善。然而，SX 的作用机制尚不清楚。
本研究旨在证明 SX 对体内 CRD 的影响，并确认 SX 在体外的分子机制。
采用 UPLC-Q-TOF/MS 控制 SX 和含药血清的质量，分别用于体内和体外实验。在体内，采用光剥夺小鼠模型；在体外，采用稳定敲低 Bmal1 细胞系来探讨 SX 机制。
低剂量 SX（SXL）可恢复（1）昼夜活动模式，（2）24 小时基础代谢模式，（3）肝损伤和（4）CRD 小鼠的内质网（ER）应激。CRD 降低了 ZT15 时肝脏的 Bmal1 蛋白，而 SXL 治疗则逆转了这一现象。此外，SXL 降低了 Grp78/ATF4/Chop 的 mRNA 表达和 ZT11 时的 ATF4/Chop 蛋白表达。体外实验中，SX 通过增加 Bmal1 蛋白的表达，降低了 thapsigargin（tg）诱导的 p-eIF2α/ATF4 通路蛋白表达，提高了 AML12 细胞的活力。
SXL 通过上调肝脏中 Bmal1 蛋白的表达，抑制 p-eIF2α/ATF4 蛋白表达，缓解 CRD 诱导的 ER 应激，提高细胞活力。
