ABSTRACT
Aim To predict the targets of Modified Danggui Shaoyao San ( MDSS) in the treatment of chronic atrophic gastritis ( CAG) based on network pharmacology and vertify the results based on experim-ention. Methods TCMSP, SWISS TARGETS, GENE CARDS and OMIM databases were used to screen the therapeutic targets of MDSS for CAG. STRING database and Cytoscape software were used to construct the protein interaction network and screen the core targets. Metascape database was used for GO analysis and KEGG enrichment pathways. And molecular docking was used for target validation. CAG rat model was pre¬pared by N-methyl-N'-nitroso-N-nitroguanidine free drink combined with sodium salicylate gastric lavage. The pathology of rat gastric mucosa was observed by hematoxylin-eosin staining,and the ultrastructure of ep¬ithelial cells was observed by transmission electron mi-croscopy. The serum IL-6 and IL-10 content was detected by enzyme-linked immunosorbent assay, and the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in rats was detected by qPCR and Western blot. Results MDSS acted on 189 targets, mainly involved in response to oxidative stress and apoptotic signaling pathway. KEGG analysis related to pathways in cancer and JAK-STAT signaling pathway. The experimental results showed that the MDSS could improve the degree of atrophy of gastric mucosa in CAG rats and improve the status of epithelial cells, down-regulate the serum IL-6 content of CAG rats, up-regulate the IL-10 content, and reduce the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in gastric mucosa with statistical significance. Conclusions MDSS treats CAG through multiple active ingredients, targets, and pathways, the mechanism of which may be related to the inhibition of the JAK2/STAT3 signaling pathway.
ABSTRACT
Background: Depression in Chronic Kidney Disease (CKD) seriously affects the prognosis of patients and Modified Danggui-Shaoyao-San (MDSS) is based on the traditional Chinese formula Danggui-Shaoyao-San (DSS) for the treatment of depression, which is further optimized. The aim of this study was to evaluate the clinical efficacy and safety of MDSS for the treatment of depression in CKD, and to explain the molecular mechanism of MDSS for the treatment of depression in CKD through pharmacology and molecular docking. Methods: 62 patients were randomly divided into treatment group (treated with MDSS) and control group (treated with placebo) and assessed by Hamilton Depression Scale, and the primary outcome was to evaluate the efficacy of MDSS in improving depressive symptoms and the effect on liver and kidney function, electrolytes. In addition, we identified the core compounds and potential targets of MDSS through the TCMSP database. The GeneCards, OMIM and Disgenet databases were then used to identify molecular targets for CKD and depression. The target protein-protein interaction network was built using STRING database. Core targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Molecular docking was used to verify the relationship between core active compounds and proteins. Results: Clinical results showed that CKD patients in the MDSS group had significantly improved depressive status with no significant adverse effects. By network pharmacology analysis, we found that the compound-target network mainly contained 47 compounds and 69 corresponding targets. 844 terms were analyzed by GO enrichment, and 254 signaling pathways in KEGG. Molecular docking showed that the top active compounds had high affinity with four targets. Conclusion: We preliminarily investigated the efficacy of MDSS in the treatment of depression in CKD and revealed the characteristics of multiple compounds and multiple targets in MDSS.
Subject(s)
Depression , Renal Insufficiency, Chronic , Humans , Molecular Docking Simulation , Depression/drug therapy , Treatment Outcome , Renal Insufficiency, Chronic/drug therapyABSTRACT
Objective: To explore the effect of modified Danggui Shaoyao San on matrix metalloproteinase-2(MMP-2), intercellular adhesion molecule-1 (ICAM-1), emorheology and inflammation in patients with chronic pelvic inflammatory disease. Method: Patients with chronic pelvic inflammatory disease during May 2017 to June 2018 were randomly divided into treatment group and control group, with 37 cases in each group. The control group was orally treated with levofloxacin tablets and metronidazole tablets. In addition to the therapy of the control group, the treatment group was also given modified Danggui Shaoyao San. Traditional Chinese medicine(TCM) symptom scores, MMP-2 and ICAM-1, interleukin-1β(IL-1β), IL-6, IL-4, IL-10, and transforming growth factor-β (TGF-β), grain-megakaryocyte colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-α), whole blood viscosity (ηb), plasma viscosity (ηp), erythrocyte aggregation index (AI), fibrinogen (Fib) before and after treatment were compared between two groups. The efficacy, adverse reactions and recurrence were observed in two groups. Result: The clinical efficacy of treatment group was better than that of the control group (Z=2.791, PPα, IL-1β, IL-6, GM-CSF,ηb,ηp, AI, Fib levels in the treatment group after treatment were significantly lower than those in control group (Pβ1 levels in treatment group after treatment were significantly higher than those in control group (Pχ2=6.198, PConclusion: Modified Danggui Shaoyao San has a significant clinical efficacy in the treatment of CPID, and can effectively relieve clinical symptoms and greatly reduce the recurrence rate, which may be related to the improvement of the regulation of MMP-2 and ICAM-1 levels, the inhibition of inflammatory reactions and the improvement of hemorheology.
