Abstract
Baihe Jizihuang Tang (BHT) is a traditional Chinese medicine (TCM) prescription, which can also be used as a nutritional food with medicinal value. Herein, we aimed to clarify the antidepressive effects and molecular mechanism of BHT. Network pharmacological analysis; chronic unpredictable mild stress (CUMS) rat model assessment; behavioral tests; analysis of hippocampal neurotransmitter levels, hippocampal pathological structure, and hypothalamic-pituitary-adrenal (HPA) axis; western blot analysis; 16s RNA sequencing; ultraperformance liquid chromatography (UPLC)/mass spectrometry (MS); and high-performance liquid chromatography (HPLC)/ultraviolet (UV) analysis were used. We found 8 potentially active components and 12 targets from the database. KEGG analysis suggested that BHT significantly affected BDNF/tyrosine receptor kinase B levels, glutamate binding, synaptic transmission based on neurotransmitter signal, and the response to glucocorticoid signaling pathways. Consistently, 7 chemical components were identified using UPLC/quadrupole time-of-flight/MS; among them, regalosides A, B, C, and E were unique components of lily of TCM, and their content in BHT was significantly different: regaloside A > B > E > C. BHT could nourish hippocampal neurons, affect neurotransmitter metabolism, reduce HPA axis hyperactivity, improve deficits in hippocampal tissue structure, and change depressive behavior. Moreover, BHT regulated BDNF expression in the hippocampus and improved intestinal flora deficits in CUMS rats by changing the content of Bifidobacterium, Rothia, Glutamicibacter, and Lactobacillus at the genus level. Collectively, BHT attenuated CUMS-induced depression-like behavior by regulating BDNF and intestinal flora disorder through the brain-gut axis. Therefore, including BHT in the medication list may constitute a potential strategy for preventing depression.
Highlights
Depression is a chronic mood disorder involving a complex pathophysiological process with multiple mechanisms
After removing compounds lacking target prediction and repeated data, screening was carried out on the SwissADME database, and 28 active compounds of lily and egg yolk with better druggability, as well as 254 targets, were selected. e drug-chemical-target network was plotted in Cytoscape software, as shown in Figure 1(a). rough topological analysis of the network of “drug-chemical-target,” we found that the obtained topological parameters were two times the median value of the degree, which was 10, and the median values of betweenness centrality (BC) and closeness centrality (CC) were 0.003235205 and 0.3559322, respectively
Network pharmacology studies suggested that the brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway, PI3K/AKT signaling pathway, synaptic neurotransmission, and choline metabolism are potential signaling pathways mediating the antidepressant efficacy of Baihe Jizihuang Tang (BHT). is study shows the characteristics of multicomponent, multitarget, and multipathway analyses, which can provide a reference for experimental animal research on the antidepressive mechanisms of BHT
Summary
Depression is a chronic mood disorder involving a complex pathophysiological process with multiple mechanisms. In 2017, the World Health Organization (WHO) announced that the global prevalence of depression had risen to 4.4%, with 322 million patients, and that depression was associated with a lifetime prevalence rate of about 16% [1]. Without timely detection and effective treatment, depression seriously affects the patient’s family and social functioning and may even lead to suicide [2]. Emerging evidence suggests that the hypothalamic–pituitary–adrenal (HPA) axis, neurotransmitters, intestinal flora, and brain-derived neurotrophic factor (BDNF) are involved in the pathology of depression. As a mediator of stress responses of the neuroendocrine system, the HPA axis is important for the multiple and complex interactions between the endocrine and immune systems [3].
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