RESUMEN

BACKGROUND: The microbiota-gut-brain axis plays a critical role in neuropsychiatric disorders, particularly anxious depression, and attracts more attention gradually. Zhi Zi Chi decoction (ZZCD) consisting of Gardenia jasminoides J. Ellis and Glycine max (L.) Merr, is a classic formula in clinic and widely applied in anxiety and depression treatment. However, the underlying mechanisms of regulating microbiota-gut-brain axis in the treatment of anxious depression by oral administration of ZZCD remain elusive. MATERIALS AND METHODS: In this project, we clarified the origin and preparation methods of the Gardenia jasminoides J. Ellis and Glycine max (L.) Merr and examined the chemical ingredients of ZZCD by liquid chromatograph mass spectrometer. Then, corticosterone combined with chronic restraint stress was applied to establish an anxious depression model. After treated with ZZCD standard decoction, based on enzyme-linked immunosorbent assay (ELISA), 16S rRNA technology, high-throughput sequencing, quantitative RT-PCR and fecal microbiota transplantation (FMT), the multiple associations between nucleus accumbens and intestinal flora in anxious depression mice were determined to clarify the mechanism of ZZCD in the treatment of anxiety and depression disorder. RESULTS: We found various substances with antidepressant and antianxiety properties in ZZCD such as rosiridin and oleanolic acid. ZZCD could alleviate depressive and anxiety behaviors in anxious depression mice via regulating the disturbance of gut microbiota. Meanwhile, the bioactive compounds of ZZCD might directly active on neurodevelopment and neuroimmune-related genes. Furthermore, the secretion of prolactin and estrogen, and interfering with mitogen-activated protein kinase (MAPK) and tumor necrosis factor (TNF) signaling pathways were mainly involved in the multi-target therapeutic effects of ZZCD against anxiety and depression. CONCLUSIONS: These findings suggested that ZZCD exerts antidepressant effects pleiotropically through modulating the microbiota-gut-brain.

Asunto(s)

Medicamentos Herbarios Chinos , Gardenia , Ratones , Animales , Depresión/tratamiento farmacológico , Depresión/etiología , Gardenia/química , Corticosterona , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Eje Cerebro-Intestino , ARN Ribosómico 16S , Semillas/química , Antidepresivos

RESUMEN

Depression is characterized by a significant and persistent decline in mood and is currently a major threat to physical and mental health. Traditional Chinese medicine can effectively treat depression with few adverse effects. Therefore, this study aimed to examine the use of reverse network pharmacology and computer simulations to identify effective ingredients and herbs for treating depression. Differentially expressed genes associated with depression were obtained from the Gene Expression Omnibus database, after which enrichment analyses were performed. A protein-protein interaction network was constructed using the STRING database to screen core targets. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used to screen ingredients related to these core targets, and the core ingredients were screened by constructing the "Targets-Ingredients-Herbs" network. Drug evaluation analysis was performed using the SwissADME and ADMETlab platforms, according to Lipinski Rule of 5. The binding between the targets and ingredients was simulated using molecular docking software. The binding stability was determined using molecular dynamics analysis. The "Ingredients-Herbs" network was constructed, and we annotated it for its characteristics and meridians. Finally, the selected herbs were classified to determine the formulation for treating depression in traditional Chinese medicine. The pathogenesis of depression was associated with changes in SPP1, Plasminogen activator inhibitor 1, CCNB1 protein, CCL3, and other genes. Computer simulations have verified the use of quercetin, luteolin, apigenin, and other ingredients as drugs for treating depression. Most of the top 10 herbs containing these ingredients were attributed to the liver meridian, and their taste was symplectic. Perilla Frutescen, Cyperi Rhizoma, and Linderae Radix, the main components of "Tianxiang Zhengqi Powder," can treat depression owing to Qi stagnation. Epimedium and Citicola, the main traditional Chinese herbs in "Wenshen Yiqi Decoction," have a positive effect on depression of the Yang asthenia type. Fructus Ligustri Lucidi and Ecliptae Herba are from the classic prescription "Erzhi Pills" and can treat depression of the Yin deficiency type. This study identified the key targets and effective medicinal herbs for treating depression. It provides herbal blend references for treating different types of depression according to the theory of traditional Chinese medicine.

Asunto(s)

Medicamentos Herbarios Chinos , Simulación de Dinámica Molecular , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Mapas de Interacción de Proteínas , Antidepresivos , Medicina Tradicional China

RESUMEN

Depression is a common mental disease, with some patients exhibiting ideas and behaviors such as self-harm and suicide. The drugs currently used to treat depression have not achieved good results. It has been reported that metabolites produced by intestinal microbiota affect the development of depression. In this study, core targets and core compounds were screened by specific algorithms in the database, and three-dimensional structures of these compounds and proteins were simulated by molecular docking and molecular dynamics software to further study the influence of intestinal microbiota metabolites on the pathogenesis of depression. By analyzing the RMSD gyration radius and RMSF, it was finally determined that NR1H4 had the best binding effect with genistein. Finally, according to Lipinski's five rules, equol, genistein, quercetin and glycocholic acid were identified as effective drugs for the treatment of depression. In conclusion, the intestinal microbiota can affect the development of depression through the metabolites equol, genistein and quercetin, which act on the critical targets of DPP4, CYP3A4, EP300, MGAM and NR1H4.

Asunto(s)

Microbioma Gastrointestinal , Biología de Sistemas , Humanos , Depresión/tratamiento farmacológico , Equol , Genisteína/farmacología , Genisteína/uso terapéutico , Simulación del Acoplamiento Molecular , Quercetina/farmacología , Quercetina/uso terapéutico

RESUMEN

As a novel kind of cold roller steel, Cr8 alloy steel has the characteristics of high hardness, high wear resistance and good toughness, which can effectively prolong the service life of the roller that is an important part of the steel rolling mill. How to accurately define the constitutive model parameters of metal materials is the major problem, because it seriously affects the accuracy of numerical simulation results of the roller hot forming process. In the study of Cr8 alloy steel's thermal deformation behavior of the present paper, the high temperature compression test was done on a Gleebel-1500D thermal/force simulation testing machine. A novel method of parameter identification was proposed based on inverse optimization. The Hansel-Spittel constitutive model was established by using the inverse optimization method. To carry out the verification on the accuracy of the established constitutive model, the predicted flow-stress of constitutive model was made a contrast to the experimental flow-stress, and the standard statistical parameters were also applied to further evaluation. The results showed a relatively high prediction accuracy of the Hansel-Spittel constitutive model based on the inverse optimization algorithm. Meanwhile, to obtain optimal parameters of Cr8 alloy steel in the thermal processing, 3D thermal processing maps concerning strain-rate, strain and temperature were built based on the dynamic material model. According to the 3D processing map, the most adequate thermal processing parameters of Cr8 alloy steel were obtianed as follows: strain 0.2-0.4, strain-rate 0.05-0.005 s-1, temperature 1100-1150 °C.