A systems pharmacology-oriented discovery of a new therapeutic use of the TCM formula Liuweiwuling for liver failure.

Multiple components of traditional Chinese medicine (TCM) formulae determine their treatment targets for multiple diseases as opposed to a particular disease. However, discovering the unexplored therapeutic potential of a TCM formula remains challenging and costly. Inspired by the drug repositioning methodology, we propose an integrated strategy to feasibly identify new therapeutic uses for a formula composed of six herbs, Liuweiwuling. First, we developed a comprehensive systems approach to enrich drug compound-liver disease networks to analyse the major predicted diseases of Liuweiwuling and discover its potential effect on liver failure. The underlying mechanisms were subsequently predicted to mainly attribute to a blockade of hepatocyte apoptosis via a synergistic combination of multiple effects. Next, a classical pharmacology experiment was designed to validate the effects of Liuweiwuling on different models of fulminant liver failure induced by D-galactosamine/lipopolysaccharide (GalN/LPS) or thioacetamide (TAA). The results indicated that pretreatment with Liuweiwuling restored liver function and reduced lethality induced by GalN/LPS or TAA in a dose-dependent manner, which was partially attributable to the abrogation of hepatocyte apoptosis by multiple synergistic effects. In summary, the integrated strategy discussed in this paper may provide a new approach for the more efficient discovery of new therapeutic uses for TCM formulae.

[Inhibitory effect and mechanism of deoxyschizandrin on NLRP3 inflammasome].

This study was conducted to investigate the inhibitory effect and the molecular mechanism of deoxyschizandrin on the activity of NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome. Bone marrow-derived macrophages were used to study the effects of deoxyschizandrin on inflammasome activation using inflammasome inducers (ATP and nigericin). Cytotoxic effect was evaluated with CCK-8. The expression of IL-1ß, caspase-1 in the supernatant and the expression of pro-caspase-1, pro-IL-1ß, ASC, NLRP3 in cell was detected by Western blot for the inhibitory effect of deoxyschizandrin (25, 50, 100 and 200 µmol·L(−1)) on the activity of NLRP3 inflammasome. Immunofluorescence was applied to investigate NF-κB (p65) transportation to the nucleus. The results of CCK-8 showed that the optimum concentration of deoxyschizandrin was 6.25­400 µmol·L(−1). Deoxyschizandrin (25, 50, 100, and 200 µmol·L(−1)) could inhibit the activation of NLRP3 inflammasome caused by nigericin and ATP, and inhibit the secretion of IL-1ß, which was associated with inhibiting the cleavage of pro-caspase-1. The results of immunofluorescence and Western blot also suggest that the inhibitory activity of deoxyschizandrin on NLRP3 inflammasome was not dependent on NF-κB pathway and protein expression of NLRP3, ASC, pro-caspase-1 and pro-IL-1ß mediated by NF-κB. Our results confirmed that deoxyschizandrin could suppress the cleavage of pro-caspase-1 and inhibit the activity of NLRP3 inflammasome at 25­200 µmol·L−1 to reduce the inflammation response.This study was conducted to investigate the inhibitory effect and the molecular mechanism of deoxyschizandrin on the activity of NLRP3 (NOD-like receptor family,pyrin domain containing 3) inflammasome.Bone marrow-derived macrophages were used to study the effects of deoxyschizandrin on inflammasome activation using inflammasome inducers (ATP and nigericin). Cytotoxic effect was evaluated with CCK-8.The expression of IL-1ß,caspase-1 in the supernatant and the expression of pro-caspase-1,pro-IL-1ß,ASC,NLRP3 in cell was detected by Western blot for the inhibitory effect of deoxyschizandrin (25, 50, 100 and 200 µmol·L(-1)) on the activity of NLRP3 inflammasome. Immunofluorescence was applied to investigate NF-κB (p65) transportation to the nucleus. The results of CCK-8 showed that the optimum concentration of deoxyschizandrin was 6.25-400 µmol·L(-1). Deoxyschizandrin (25, 50, 100,and 200 µmol·L(-1)) could inhibit the activation of NLRP3 inflammasome caused by nigericin and ATP, and inhibit the secretion of IL-1ß, which was associated with inhibiting the cleavage of pro-caspase-1.The results of immunofluorescence and Western blot also suggest that the inhibitory activity of deoxyschizandrin on NLRP3 inflammasome was not dependent on NF-κB pathway and protein expression of NLRP3,ASC,pro-caspase-1 and pro-IL-1ßmediated by NF-κB. Our results confirmed that deoxyschizandrin could suppress the cleavage of pro-caspase-1 and inhibit the activity of NLRP3 inflammasome at 25-200 µmol·L(-1) to reduce the inflammation response.

[Proceedings of new drug delivery systems and their applications in the traditional Chinese drugs].

By referred to a lot of data, some new drug delivery systems(DDSs) including the Sustained and Controlled DDS, the Targeted DDS, the Transdermal DDS, the Bioadhensive DDS, the PowderJect DDS and the Self-Emulsifying DDS and their applications in TCD since 2000, will be summarized and some latest DDSs in the world including drug-eluting stents, gene therapy carrier system, biological chip, biomolecular motor-powered nanodevice and nanotrap will be also introduced in this paper. The objective of this paper is to introduce the new DDSs proceedings of and their applications in the Traditional Chinese Drugs(TCDs) and to provide some references for the pharmaceutics of TCD. For several recent years, the great success have been achieved in studying the new DDS application in the change of preparation of TCD by the investigators at home, but there is a large difference between at home and at board. So it is necessary to make a greater advance. During the modernization of TCD, there is an effective way that the new drug delivery systems(DDSs) will be applied in the change of the preparation of TCD.