Anxiety disorder is one of the most common mental diseases. It is mainly characterized by a sudden, recurring but indescribable panic, fear, tension and/or anxiety. Yangshendingzhi granules (YSDZ) are widely used in the treatment of anxiety disorders, but its active ingredients and underlying mechanisms are not yet clear. This study integrates network pharmacology and metabolomics to investigate the potential mechanism of action of YSDZ in a rat model of anxiety. First, potential active ingredients and targets were screened by network pharmacology. Then, predictions were verified by molecular docking, molecular dynamics and western blotting. Metabolomics was used to identify differential metabolites and metabolic pathways. All results were integrated for a comprehensive analysis. Network pharmacology analysis found that Carotene, β-sitosterol, quercetin, Stigmasterol, and kaempferol in YSDZ exert anxiolytic effects mainly by acting on IL1β, GABRA1, PTGS1, ESR1, and TNF targets. Molecular docking results showed that all the affinities were lower than −5 kcal/mol, and the average affinities were −7.7764 kcal/mol. Molecular dynamics simulation results showed that RMSD was lower than 2.5 A, and the overall conformational changes of proteins were small, indicating that the small molecules formed stable complexes with proteins. The results of animal experiments showed that YSDZ exerts anxiolytic effects by regulating GABRA1 and TNF-α, ameliorating pathological damage in hippocampal CA1, and regulating metabolic pathways such as thiamine, cysteine and methionine metabolism, lysine biosynthesis and degradation. Altogether, we reveal multiple mechanisms through which YSDZ exerts its anti-anxiety effects, which may provide a reference for its clinical application and drug development.
Depression is a serious psychological disorder with a rapidly increasing incidence in recent years. Clinically, selective serotonin reuptake inhibitors are the main therapy. These drugs, have serious adverse reactions, however. Traditional Chinese medicine has the characteristics of multiple components, targets, and pathways, which has huge potential advantages for the treatment of depression. The antidepressant potential of the herbal combination of Bupleurum chinense DC (Chaihu) and Paeonia lactiflora Pall (Baishao) has been extensively studied previously. In this review, we summarized the antidepressant active components and mechanism of Chaihu-Baishao herb pair. We found that it works mainly through relieving oxidative stress, regulating HPA axis, and protecting neurons. Nevertheless, current research of this combined preparation still faces many challenges. On one hand, most of the current studies only stay at the level of animal models, lacking of sufficient clinical double-blind controlled trials for further verification. In addition, studies on the synergistic effect between different targets and signaling pathways are scarce. On the other hand, this preparation has numerous defects such as poor stability, low solubility, and difficulty in crossing the blood-brain barrier.
经前期综合征( Premenstrual Syndrome,PMS)为育龄女性高发病,经前烦躁障碍症( Premenstrual Dyspho-ric Disorder,PMDD)为其重症类型,表现为经前规律性出现情绪障碍及不适的躯体症状,影响多达80%的女性,月经来潮后消失或减轻,若不治疗,则伴随女性三十多年直到更年期[1,2].临床上,焦虑与抑郁情绪是P MDD患者典型表现,同时伴有学习记忆能力受损,并呈现一些列不适的躯体症状,如注意力不集中、易激动、嗜睡、焦虑[3].而且,烦躁、疲劳和食欲变化,情绪低落和焦虑等也是其主要症状表现,且大多数症状为中度严重.另有孙文君等[4]对多中心人群调查后发现:患者情志抑郁、焦虑且工作能力下降、学习能力下降.