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Significant changes in pharmacokinetic parameters of EP, PEP and MEP were observed after oral administration with different combinations. The pharmacokinetic results reported here might provide reference for clinical usage of Ephedra alkaloids.

Objective. To clarify the therapeutic mechanisms of compound Xuanju capsule-treated rheumatoid arthritis (RA) based on network pharmacology tactics. Method. The TCMSP, TCMID and STITCH databases were used to screen the active ingredients and targets in the compound Xuanju capsule; the OMIM, TTD, PharmGKB and GeneCards databases were applied to screen the RA-related disease targets. Then, the obtained targets were imported into Cytoscape 3.7.1 software to construct the active ingredient-target network and the RA-related disease-target network. The active ingredient-target PPI network, the RA-related disease-target PPI network and the common target PPI network were built by using the STRING platform and Cytoscape 3.7.1 software. The GO and KEGG analyses of the common targets were analyzed by using the Metascape and Bioinformatics online tools. Results. A total of 51 active ingredients and 513 corresponding ingredient targets were harvested from the compound Xuanju capsule; 641 RA-related disease targets were obtained. After two PPI networks were constructed and merged, 116 RA-related targets of compound Xuanju capsules were identified and analyzed. 116 RA-related targets of compound Xuanju capsules are mainly involved in the biological processes and molecular functions, such as the cytokine-mediated signaling pathways, the response to lipopolysaccharide and the blood vascular development, the cytokine activity, the cytokine receptor binding and the receptor regulator activity. Furthermore, 116 RA-related targets of compound Xuanju capsules are concentrated in signaling pathways such as the IL-17, TNF, Th17 cell differentiation, Toll receptor and RA signaling pathway. Conclusion. The compound Xuanju capsule had the action characteristics of multiple components, multiple targets, and multiple pathways in the treatment of RA, which might primarily reduce the release of proinflammatory factors (such as IL-6 and TNF-α) and increase the production of anti-inflammatory factors (such as IL-10) by regulating inflammation-related signaling pathways (such as IL-17), thereby alleviating the inflammatory damage and improving the bone tissue repair.

Objective To study the pharmacological mechanism of Shanhaidan granules for treatment of coronary heart disease angina pectoris(CHD-AP). Methods The active ingredients and their target genes of Shanhaidan granules were collected from TCMSP and TCMID. CHD-AP-related target genes were collected from GeneCards, OMIM and DurgBank database. The target PPI network was constructed by STRING. PPI network was used for topological analysis and core target screening. The hub target proteins and top core ingredients of Shanhaidan Granule on CHD-AP was analysed for the binding validation experiment by Molecular Docking. Results 198 active components and 320 potential targets were obtained from Shanhaidan granule, 1208 related targets and 158 joints of CHD-AP were screened. PPI network analysis showed that AKT1, IL-6, VEGF, TNF, MAPK, Caspase-3, MMP, and EGFR were the core and key teagets in treatment of CHD-AP with Shanhaidan granule. KEGG-GO analysis indicated that Shanhaidan granules treated CHD-AP by regulating the TNF signaling pathway, IL-17 signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway and apoptosis-related signalling pathway. The results of the molecular docking showed that the core compounds and target proteins had strong binding activity. Conclusion The results predicted and verified mechanism of Shanhaidan granule gainst CHD-AP from a holistic perspective, which provided theoretical support for rational clinical application of CHD-AP.