In recent years， the field of network pharmacology （NP） has developed rapidly， but the flawed and routine workflow has seriously affected the scientificity and reliability of NP analysis results. For complex diseases caused by environmental and genetic factors， symptomatic treatment or drugs targeting a single pathophysiological process cannot prevent or delay the progression of the disease， so the drug development fails or withdraws from the market. Therefore， there is an urgent need to develop new ideas for NP analysis that combines multiple pathophysiological processes. The key pathophysiological process is an important and complete set of pathological changes in the process of the occurrence， development， and outcome of the disease， which represents the current comprehensive and profound understanding of the nature of the disease. In order to improve the quality of NP research and promote the healthy development of the NP field， this paper proposes a new idea of NP analysis based on key pathophysiological processes. Based on the long-term clinical practice of traditional Chinese medicine and the key pathophysiological process of the disease， the method comprehensively analyzes the pharmacological mechanism and active ingredients of traditional Chinese medicine compound from the perspective of key pathophysiological process， which increases the scientifically， reliability， and repeatability of the analysis results. This paper takes Alzheimer's disease （AD） as an example to illustrate the necessity， feasibility， main workflow， advantages， and disadvantages of this method， and it is expected to screen disease-modifying drugs that prevent or reverse the course of the disease and promote the clinical transformation of research results.

Depression is a kind of complex mental illness， which is mainly treated by western medicine at present， but the effect of western antidepressant drugs is not good due to the combined influence of side effects and individual differences of patients. Depression is a "stagnation syndrome" in traditional Chinese medicine， and its treatment principle is to disperse stagnated liver Qi for relieving Qi stagnation. The classic traditional Chinese medicine formula Chaihu Shugansan （CHSGS） has a long history of treating depression and demonstrates significant therapeutic efficacy. Clinically， the addition and subtraction of CHSGS is flexible， but the properties of the active ingredients are vague， and the mechanism and function are unclear. In order to elucidate the pharmacodynamic basis and antidepressant mechanism of CHSGS， this article reviews the pharmacodynamic material basis of CHSGS， clinical research and antidepressant mechanism research progress. Clinically， CHSGS can treat various types of depression such as primary depression， post-stroke depression， and postpartum depression. This article summarizes 32 main ingredients of CHSGS， among which albiflorin， ferulic acid， naringin， hesperidin， saikosaponin a， glycyrrhetinic acid， tangeretin， meranzin hydrate， nobiletin and glycyrrhizic acid are the quality markers （Q-markers） for the antidepressant effect of CHSGS. The antidepressant mechanism of CHSGS is complex， including regulating monoamine neurotransmitters， hypothalamic-pituitary-adrenal （HPA） axis， neurotrophic factors， inflammatory response， cell damage-related pathways， oxidative stress， etc. This article helps to deeply understand the pharmacodynamic basis and mechanism of CHSGS in treating depression， and provides a theoretical basis for the clinical application of CHSGS in treating depression and the development of antidepressant drugs.

Post-stroke depression (PSD) is a serious and common complication of stroke, which seriously affects the rehabilitation of stroke patients. To date, the pathogenesis of PSD is unclear and effective treatments remain unavailable. Here, we established a mouse model of PSD through photothrombosis-induced focal ischemia. By using a combination of brain imaging, transcriptome sequencing, and bioinformatics analysis, we found that the hippocampus of PSD mice had a significantly lower metabolic level than other brain regions. RNA sequencing revealed a significant reduction of miR34b-3p, which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E (eIF4E). Furthermore, silencing eIF4E inactivated microglia, inhibited neuroinflammation, and abolished the depression-like behaviors in PSD mice. Together, our data demonstrated that insufficient miR34b-3p after stroke cannot inhibit eIF4E translation, which causes PSD by the activation of microglia in the hippocampus. Therefore, miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.
Animals ; Mice ; Depression ; Eukaryotic Initiation Factor-4E/metabolism* ; MicroRNAs/metabolism* ; Neurons/metabolism* ; Stroke/metabolism*