■探讨Sugemule-4汤(MMS-4D)治疗失眠的潜在分子机制。
■使用DL-4-氯苯丙氨酸(PCPA)+慢性不可预测的轻度应激刺激(CUMS)诱导大鼠失眠模型。模型建立成功后,MMS-4D在低位介入,中等,和高剂量7天。采用开场试验(OFT)对疗效进行初步评价。利用肠道菌群研究了MMS-4D治疗失眠的潜在机制。血清代谢组学,和网络药理学(NP)。使用ELISA和Westernblot对关键途径的主要成分进行实验验证。
■失眠模型大鼠体重显著升高(p≤0.05),OFT中的总运动距离增加(p≤0.05),休息时间缩短,站立次数增加(p≤0.05),用MMS-4D治疗后。此外,5-HT有实质性的恢复,DA,GABA,和大鼠下丘脑组织中的Glu水平以及结肠组织中的5-HT和GABA水平。药物治疗后失眠大鼠海马DAT和DRD1蛋白表达降低。MMS-4D可以通过调节不同的关键途径来治疗失眠,包括5-HT-,DA-,GABA-,和Glu介导的神经活性光接收器相互作用,cAMP信号通路,血清素能,谷氨酸能,多巴胺能,和GABA能突触。
■本研究揭示MMS-4D可以改善失眠模型大鼠的一般状态和行为改变。其机制可能与逆转5-HT介导的异常通路有关,DA,GABA,还有Glu,如5-羟色胺能突触,多巴胺能突触,谷氨酸能突触,和GABA能突触。
UNASSIGNED: To explored the potential molecular mechanism of Sugemule-4 decoction (MMS-4D) in treating
insomnia.
UNASSIGNED: DL-4-chlorophenylalanine (PCPA) + chronic unpredictable mild stress stimulation (CUMS) was used to induce an
insomnia model in rats. After the model was successfully established, MMS-4D was intervened at low, medium, and high doses for 7 days. The open-field test (OFT) was used to preliminarily evaluate the efficacy. The potential mechanism of MMS-4D in treating insomnia was investigated using gut microbiota, serum metabolomics, and network pharmacology (NP). Experimental validation of the main components of the key pathways was carried out using ELISA and Western blot.
UNASSIGNED: The weights of the
insomnia-model rats were significantly raised (p ≤ 0.05), the total exercise distance in the OFT increased (p ≤ 0.05), the rest time shortened, and the number of standing times increased (p ≤ 0.05), after treatment with MMS-4D. Moreover, there was a substantial recovery in the 5-HT, DA, GABA, and Glu levels in the hypothalamus tissue and the 5-HT and GABA levels in the colon tissue of rats. The expression of DAT and DRD1 proteins in the hippocampus of
insomnia rats reduced after drug treatment. MMS-4D may treat
insomnia by regulating different crucial pathways including 5-HT -, DA -, GABA -, and Glu-mediated neuroactive light receiver interaction, cAMP signaling pathway, serotonergic, glutamatergic, dopaminergic, and GABAergic synapses.
UNASSIGNED: This study revealed that MMS-4D can improve the general state and behavioral changes of insomnia model rats. Its mechanism may be related to the reversal of abnormal pathways mediated by 5-HT, DA, GABA, and Glu, such as Serotonergic synapse, Dopaminergic synapse, Glutamatergic synapse, and GABAergic synapse.