School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China.
School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China.
J Chem Neuroanat. 2023 Dec;134:102349. doi: 10.1016/j.jchemneu.2023.102349. Epub 2023 Oct 23.
Depression is a common but serious sickness which causes a considerable burden on individuals and society. Recently, it has been well established that the occurrence of depression was related to the microbiota-gut-brain axis. The toll-like receptor 4 (TLR4)/ nuclear factor kappa-B kinase (NFκB)/ NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway is closely associated with the regulation of microbiota-gut-brain axis. Suanzaoren Decoction (SZRD), which recorded in Jin Gui Yao Lve in Han dynasty, has been used for treating insomnia and depression for a long time. However, the action mechanism of the depression regulation through the TLR4/NFκB/NLRP3 pathway by SZRD was still unclear. In this study, SZRD was firstly performed on a chronic unpredictable mild stress (CUMS) mice model. The results of behavioral tests showed that SZRD treatment could ameliorate the depressive-like behaviors of CUMS mice effectively. According to our previous researches about the components of SZRD in vitro and in vivo, the identification of serum metabolites in depression model rats was further analyzed qualitatively using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. 27 prototypes and 44 metabolites were identified. The main types of metabolic reactions are glucuronization, sulfation, and so on. Then, using immunohistochemistry and western blotting to monitor the difference in activation of TLR4/NFκB/NLRP3 signaling pathway in mice brain and colon. The results showed that SZRD treatment could reduce expression levels of related factors. Additionally, the SZRD treatment could also inhibit the histopathological damage in the path morphology of the hippocampus and colon. The results of 16SrRNA demonstrated that SZRD could reduce the dysbiosis of the intestinal flora of depressive mice. The above results provided important information for studying the action mechanism of SZRD in treating depression by regulating microbiota-gut-brain axis via inhibiting TLR4/NFκB/NLRP3 pathway.
抑郁症是一种常见但严重的疾病，它给个人和社会带来了相当大的负担。最近，人们已经充分认识到抑郁症的发生与微生物群-肠道-大脑轴有关。 Toll 样受体 4（TLR4）/核因子 kappa-B 激酶（NFκB）/NOD 样受体热蛋白结构域相关蛋白 3（NLRP3）途径与微生物群-肠道-大脑轴的调节密切相关。《金匮要略》中记载的酸枣仁汤（SZRD）长期以来一直用于治疗失眠和抑郁症。然而，SZRD 通过 TLR4/NFκB/NLRP3 途径调节抑郁症的作用机制仍不清楚。在这项研究中，SZRD 首先在慢性不可预测轻度应激（CUMS）小鼠模型上进行了研究。行为测试结果表明，SZRD 治疗可有效改善 CUMS 小鼠的抑郁样行为。根据我们之前关于 SZRD 在体外和体内的成分研究，进一步使用超高效液相色谱四极杆飞行时间质谱对抑郁模型大鼠血清代谢物进行定性分析。鉴定出 27 个原型和 44 个代谢物。主要的代谢反应类型是糖基化、硫酸化等。然后，使用免疫组织化学和 Western blot 监测 TLR4/NFκB/NLRP3 信号通路在小鼠大脑和结肠中的激活差异。结果表明，SZRD 治疗可降低相关因子的表达水平。此外，SZRD 治疗还可以抑制海马和结肠组织形态学中的组织病理学损伤。16SrRNA 的结果表明，SZRD 可以减少抑郁小鼠肠道菌群失调。上述结果为研究 SZRD 通过抑制 TLR4/NFκB/NLRP3 通路调节微生物群-肠道-大脑轴治疗抑郁症的作用机制提供了重要信息。
