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Network pharmacology and bioinformatics technology were used to predict the mechanism of action of Fuzi-Lizhong pill (FLP) in the treatment of ulcerative colitis (UC). 26 components (23 prototype compounds and 3 metabolites) in the blood of FLP were selected as the research objects. PharmMapper database, SwissTargetPrediction platform, GeneCards and OMIM database were used to screen and predict potential targets of FLP in blood. The protein-protein interaction network model was constructed by using String database and Cytoscape software. DAVID platform, KEGG and Reactome databases were used for GO analysis and pathway analysis of potential targets. Network of drug ingredients-targets-pathways was constructed by Cytoscape software. AutoDock vina software was used to dock the molecules of the absorbed ingredients of FLP in blood with the key targets. 82 potential targets of FLP for treatment of UC were obtained. Potential targets mainly involve biological processes such as response to organic substance, regulation of apoptosis, regulation of programmed cell death, which played roles in the treatment of UC by adjusting pathways in cancer, Colorectal cancer, Vascular endothelial growth factor signaling pathway, Mitogen-activated protein kinase signaling pathway, arachidonic acid metabolism and the other signal pathways. From the perspective of network pharmacology, this study predicted the mechanisms of action of FLP in treating UC, indicating that FLP in treating UC had the characteristics of multiple ingredients, multiple targets and multiple pathways, which laid a foundation for further research.
ABSTRACT
Objective:Based on the previous studies, to investigate the dissolution behavior of Fuzi Lizhongwan by simultaneously determining the dissolution of benzoylmesaconine, benzoylaconine and benzoylhypaconine in Aconiti Lateralis Radix Praeparata. Method:The simultaneous determination of benzoylmesaconine, benzoylaconine and benzoylhypaconine in Fuzi Lizhongwan was established by HPLC-QQQ-MS. The dissolution amounts of three compositions in 15 batches of Fuzi Lizhongwan from 5 manufacturers at different time points, the cumulative dissolution was calculated and the dissolution curve was drawn. The f2 similarity factor method was adopted to evaluate similarity of dissolution curves of index components in different batches of samples from the same manufacturer, and to evaluate similarity of dissolution curves of samples from different manufacturers based on the same index component. The dissolution model of Fuzi Lizhongwan was concluded by fitting with the dissolution data. Result:When hydrochloric acid solution with pH of 1.2 was used as the dissolution medium, the three alkaloids had the best dissolution effect. The dissolution behavior of three monoester alkaloids in Fuzi Lizhongwan was basically synchronous and the dissolution lasted for 24 h. Three batches of samples from the same manufacturer (manufacturer 1, 3, 4 and 5) appeared to be similar on dissolution behavior, indicating that the dissolution behavior of the majority of samples from different manufacturers was similar. The dissolution behavior of batch 1 sample was different from batch 2 and 3 samples in manufacturer 2, suggesting that the quality of different batches of samples in manufacturer 2 might be different. The fitting results of dissolution data of index components in samples from different manufacturers were consistent, and the Weibull model was the best. Conclusion:Index components in fifteen batches of samples from 5 manufacturers are continuously dissolved within 24 h, indicating that the samples have the characteristics of slow dissolution. The dissolution curves of samples from the same manufacturer are similar to each other, indicating that the quality of different batches of products from most manufacturers is stable. The dissolution behavior of benzoylmesaconine, benzoylaconine and benzoylhypaconine in samples form different manufacturers has some differences, which may be caused by the source of medicinal materials and preparation technology parameters.
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Objective To observe the therapeutic effect of Taoshi Jiangu Decoction for osteoporosis(OP). Methods A total of 120 cases of OP patients were randomly divided into treatment group and control group ,60 cases in each group. Patients in the treatment group were treated with Taoshi Jiangu Decoction orally,and those in the control group were treated with Caltrate D and Alendronate Sodium Tablets orally. Four weeks constituted one treatment course, and the treatment for the two groups covered 3 courses. The therapeutic effect of the two groups was evaluated by the changes of traditional Chinese medicine(TCM)syndrome scores,urine hydroxyproline (U-HYP),serum bone Gla-protein (BGP or osteocalcin),serum alkaline phosphatase (ALP),urine calcium (U-Ca),tartrate resistant acid phosphatase (TRAP), bone mass density(BMD) and quantitative CT(QCT) before and after treatment. Results (1)After treatment, the TCM syndrome scores of the two groups were decreased(P<0.05 compared with those before treatment),and the decrease in the treatment group was superior to that of the control group (P < 0.05). (2)After treatment,the levels of bone formation indexes of ALP and BGP were increased,and the levels of bone resorption indexes of U-HYP,U-Ca and TRAP were decreased in the two groups (P<0.05 compared with those before treatment). The effects of the treatment group were superior to those of the control group,the difference being statistically significant(P < 0.05).(3)After treatment,BMD of lumbar vertebrae 2-4 (L2-L4),neck of femur,Wards triangle and trochanter of femur,and QCT values of left neck of femur were obviously increased in the two groups (P < 0.05 compared with those before treatment). The treatment group showed stronger effect on increasing BMD and QCT values than the control group, the difference being statistically significant (P < 0.05). Conclusion Taoshi Jiangu Decoction can restrain bone absorption , promote bone formation and increase BMD, showing certain therapeutic effect for OP.