刺五加片(CWT)是通过浓缩和干燥干燥刺五加根茎(Rupr。&马克西姆。)马克西姆[天花科;刺五加]。此外,CWT被纳入2020年版《中国药典》,广泛应用于治疗失眠。它主要含有刺梨苷B,eleutherosideE,isofraxidin,刺梨苷C,Ciwujiatone,和绿原酸,以及其他化学成分。虽然CWT治疗失眠的临床疗效已得到证实,其功能和药理作用尚未得到系统评估,其治疗失眠的作用机制仍不清楚。因此,在这项研究中,行为,能量代谢,应用代谢组学方法系统评价CWT对失眠症的疗效。此外,基于UPLC-Q-TOF-MS/MS的尿液代谢组学用于确定失眠的潜在内源性生物标志物,检测CWT治疗前后的各种变化,探索CWT的代谢途径和潜在靶标,并揭示其药理机制。结果表明,CWT增加了抑制性神经递质(5-HT和GABA)的含量,降低了兴奋性神经递质(DA和NE)的含量。此外,CWT增强了自主行为活动,稳定的情绪,促进失眠症大鼠每日基本代谢指标恢复至正常水平。尿液代谢组学实验确定了28个潜在的内源性生物标志物,如赖氨酸,7,8-二氢蝶呤,5-膦酰氧基-L-赖氨酸,和N-乙酰血清素.CWT治疗后,22种生物标志物的含量恢复到正常水平。代表性标志物包括N-乙酰血清素,血清素,N-甲基色胺,和6-羟基褪黑素.此外,大鼠体内的代谢途径显著逆转,如色氨酸代谢,叶酸生物合成,苯丙氨酸代谢,和酪氨酸代谢。最终,结论是CWT调节色氨酸代谢,叶酸生物合成,苯丙氨酸代谢,和体内其他代谢水平。该药物已被证实通过调节5-羟色胺的含量有效治疗失眠,6-羟基褪黑激素,N-乙酰血清素,和N-甲基色胺在色氨酸代谢中达到稳定和正常的水平。
Ciwujia Tablets (CWT) are produced by concentrating and drying the extract solution of the dried rhizome of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim [Araliaceae; E. senticosus radix et rhizoma]. Besides, CWT is included in the 2020 edition of Chinese Pharmacopoeia and is widely used in the treatment of insomnia. It mainly contains eleutheroside B, eleutheroside E, isofraxidin, eleutheroside C, ciwujiatone, and chlorogenic acid, as well as other chemical components. Although the clinical efficacy of CWT in treating insomnia has been confirmed, its functions and pharmacological effects have not been systematically evaluated and its mechanism of action in the treatment of insomnia remains unclear. Therefore, in this study,
behavioral, energy metabolism, and metabonomics methods were applied to systematically evaluate the effect of CWT on insomnia. Additionally, urine metabonomics based on UPLC-Q-TOF-MS/MS were utilized to identify potential endogenous biomarkers of insomnia, detect the various changes before and after CWT treatment, explore the metabolic pathway and potential target of CWT, and reveal its pharmacological mechanism. Results revealed that CWT increased inhibitory neurotransmitter (5-HT and GABA) content and reduced the content of excitatory neurotransmitters (DA and NE). Moreover, CWT enhanced autonomous
behavioral activity, stabilized emotions, and promoted the return of daily basic metabolic indexes of insomniac rats to normal levels. The urine metabolomics experiment identified 28 potential endogenous biomarkers, such as allysine, 7,8-dihydroneopterin, 5-phosphonooxy-L-lysine, and N-acetylserotonin. After CWT treatment, the content of 22 biomarkers returned to normal levels. The representative markers included N-acetylserotonin, serotonin, N-methyltryptamine, and 6-hydroxymelatonin. Additionally, the metabolic pathways in rats were significantly reversed, such as tryptophan metabolism, folate biosynthesis, phenylalanine metabolism, and tyrosine metabolism. Ultimately, it is concluded that CWT regulated tryptophan metabolism, folate biosynthesis, phenylalanine metabolism, and other metabolic levels in the body. This drug has been confirmed to be effective in the treatment of insomnia by regulating the content of serotonin, 6-hydroxymelatonin, N-acetylserotonin, and N-methyltryptamine to a stable and normal level in tryptophan metabolism.