Search

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., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Wenyang Wei et al.)

Although Ma Huang Tang (MHT) has long been considered as a classical formula for respiratory infections like influenza, bronchitis and asthma, its chemical ingredients that really exert the main efficacy are still obscure. In this study we aimed to screen its antiviral components and investigate the potential mechanisms. The MDCK cellular research results showed that, among nine predominant ingredients of MHT, L-methylephedrin (LMEP), L-ephedrine (LEP) and D-pseudo- ephedrine (DPEP) significantly inhibited the proliferation of influenza A virus in vitro , and the inhibitory effect at 24 h after the treatment was more obvious than that at 48 h. They also significantly inhibited the mRNA expression levels of related genes in the TLR3, TLR4 and TLR7 signaling pathways, which were accompanied with the down-regulation of TNF-α level and the up-regulation of IFN-β level in the cell supernatant. Therefore, three Ephedra alkaloids exert an antiviral effect in vitro which may be closely related to the inhibition of viral replication and the modulation of inflammatory response. Animal research further indicated, at the 3rd and 7th days after infection, LEP and DPEP significantly attenuated lung injury, decreased lung index, virus load in the lung and the level of IL-1β in serum, inhibited the mRNA expression levels of TNF-α, TLR3, TLR4, TLR7, MyD88, NF-κB p65 and RIG-1 as well as the protein expression levels of TLR4, TLR7, MyD88 and NF-κB p65 and markedly increased thymus index, the level of IL-10 in serum and the mRNA expression level of IFN-γ. LEP and DPEP have certain protective effects on the influenza virus-infected mice, which may be associated with their abilities of effectively alleviating lung injury, improving the immunologic function of infected mice and adjusting the host's TLRs and RIG-1 pathways. The overall findings demonstrate that, as effective and inexpensive natural substances, Ephedra alkaloids and MHT may have potential utility in clinical management.

Ma Huang Tang (MHT), a classical Chinese herbal decoction which has been used in clinic for thousands of years, was very effective in treating the upper respiratory tract infection. But its activity against influenza virus A, the anti-inflammatory effect and the underlying mechanisms have been poorly investigated in previous researches. In this study, the antiviral efficacy of MHT directly inhibiting influenza virus A was investigated in vitro in MDCK cells. In an ICR pneumonia mouse model infected with influenza virus A PR/8/34, MHT (8, 4 and 2 g/kg) were oral administrated for 7 days after viral challenge, to evaluate the effect of MHT on ameliorating viral pneumonia and decipher the underlying mechanisms. The in vitro results showed that MHT possessed antiviral activity with low toxicity. The in vivo assays showed that MHT (8 and 4 g/kg) significantly attenuated lung histopathological changes, decreased lung index, interleukin (IL)-4,5, tumor necrosis factor alpha (TNF-α), CD3 + , CD8 + T cell levels, increased IL-2, gamma interferon (IFN-γ), CD4 + T cell levels and CD4 + /CD8 + ratio, inhibited toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor associated factor 6 (TRAF6) protein levels. All these results demonstrate that MHT can strikingly ameliorate influenza virus A pneumonia in mice, which is associated with the regulating effect of MHT in the imbalance of body's immune function and the MyD88-dependent signaling pathway of TLR4., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)