Network pharmacological analysis to reveal the mechanism governing the effect of Qin Xi Tong on osteoarthritis and rheumatoid arthritis.

INTRODUCTION: Qin Xi Tong (QXT), produced by water extracts of Caulis Sinomenii, is clinically effective in the therapy of rheumatoid arthritis (RA). It is also a complementary agent for osteoarthritis (OA). This study aimed to screen the candidate targets and identify the potential mechanisms of QXT against RA and OA. METHOD: The active ingredients contained in QXT were queried from the TCMSP database. Their predicted targets were obtained through web-based databases, including TCMSP, BATMAN-TCM, CTD, and PharmMapper. The OA and RA targets were collected from the Genecards database and the GSE55235 dataset. Based on the DAVID database, GO and KEGG enrichment analyses of disease-drug common targets predicted potential signaling pathways for QXT. In addition, core targets were identified by mapping component-target-disease interaction networks with Cytoscape 3.9.1 and STRING. The Swissdock and Pymol tools further validate the predicted results. RESULTS: A total of 161 genes were put forward as potential targets for treating RA and OA. These genes might be involved in joint inflammation, including the IL-17 signaling pathway, MAPK signaling pathway, and TNF signaling pathway. They also regulated the progression of joint injuries, such as apoptosis, Th17 cell differentiation, and osteoclast differentiation. In addition, we identified 12 core targets of QXT. Molecular docking results showed that QXT has a high affinity with these core targets. CONCLUSIONS: This study reveals the mechanism governing the effect of QXT on RA and OA, predicts the direct target, and provides new ideas for clinical treatment. Key Points • Our study reveals the underlying mechanism of QXT in the treatment of RA and OA. • Further research into the effects of compounds in QXT alone would be of interest.

Network Analysis of Se-and Zn-related Proteins in the Serum Proteomics Expression Profile of the Endemic Dilated Cardiomyopathy Keshan Disease.

Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) and zinc (Zn) deficiencies are closely related to KD. The molecular mechanism of KD pathogenesis is still unclear. There are only few studies on the interaction of trace elements and proteins associated with the pathogenesis of KD. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS) technique analysis was used to analyze the differential expression of proteins from serum samples. Comparative Toxicogenomics Database (CTD) was used to screen Se- and Zn-associated proteins. Then, pathway and network analyses of Se- and Zn-associated proteins were constituted by Cytoscape ClueGO and GeneMANIA plugins. One hundred and five differentially expressed proteins were obtained by 2DLC-MS/MS, among them 19 Se- and 3 Zn-associated proteins. Fifty-two pathways were identified from ClueGO and 1 network from GeneMANIA analyses. The results showed that Se-associated proteins STAT3 and MAPK1 and Zn-associated proteins HIF1A and PARP1, the proteins involved in HIF-1 signaling pathway and apoptosis pathway, may play significant roles in the pathogenesis of KD. The approach of this study would be also beneficial for further dissecting molecular mechanism of other trace element-associated disease.

A new kaempferol trioside from Silphium perfoliatum.

A new apiose-containing kaempferol trioside, kaempferol-3-O-α-L-rhamnosyl-(1‴ → 6″)-O-ß-D-galactopyranosyl-7-O-ß-D-apiofuranoside, along with 16 known compounds, were isolated from 50% acetone extract of Silphium perfoliatum L. Their structures were elucidated by acid hydrolysis and spectroscopic techniques including UV, IR, MS, ¹H, ¹³C, and 2D-NMR. In addition, the pharmacological activity of compound 1 was tested with HepG2 and Balb/c mice (splenic lymphocytes and thymic lymphocytes) in vitro, and it exhibited inhibitory effect on the proliferation of HepG2 cells and showed the immunosuppressive activity.

Three new ursane-type triterpenes from the leaves of Rehmannia glutinosa.

Three new ursane-type triterpenes, glutinosalactone A-C (1-3), were isolated from the 50% aqueous acetone extract of the leaves of Rehmannia glutinosa. Their structures were elucidated on the basis of spectral analysis (IR, NMR and MS spectroscopy). The cytotoxic effects of compounds 1-3 against three human cancer cell lines (MCF-7, MG63 and HepG2) were also evaluated. Compound 3 showed cytotoxic activities with IC50 values of 8.35-39.25 µM.