Metabolomics and Proteomics Annotate Therapeutic Properties of Geniposide: Targeting and Regulating Multiple Perturbed Pathways

Geniposide is an important constituent of Gardenia jasminoides Ellis, a famous Chinese medicinal plant, and has displayed bright prospects in prevention and therapy of hepatic injury (HI). Unfortunately, the working mechanisms of this compound are difficult to determine and thus remain unknown. To determine the mechanisms that underlie this compound, we conducted a systematic analysis of the therapeutic effects of geniposide using biochemistry, metabolomics and proteomics. Geniposide significantly intensified the therapeutic efficacy as indicated by our modern biochemical analysis. Metabolomics results indicate 9 ions in the positive mode as differentiating metabolites which were associated with perturbations in primary bile acid biosynthesis, butanoate metabolism, citrate cycle (TCA cycle), alanine, aspartate and glutamate metabolism. Of note, geniposide has potential pharmacological effect through regulating multiple perturbed pathways to normal state. In an attempt to address the benefits of geniposide based on the proteomics approaches, the protein-interacting networks were constructed to aid identifying the drug targets of geniposide. Six identified differential proteins appear to be involved in antioxidation and signal transduction, energy production, immunity, metabolism, chaperoning. These proteins were closely related in the protein-protein interaction network and the modulation of multiple vital physiological pathways. These data will help to understand the molecular therapeutic mechanisms of geniposide on hepatic damage rats. We also conclude that metabolomics and proteomics are powerful and versatile tools for both biomarker discovery and exploring the complex relationships between biological pathways and drug response, highlighting insights into drug discovery.     

鼠疫疫苗研究的现状与展望

鼠疫（Plague）是由鼠疫耶尔森菌(Yersina pestis，Y. pestis)（简称鼠疫菌）引起的一种烈性传染病，属甲类传染病，具有高度传染性和致病性。在过去的鼠疫大流行中近2亿感染者死亡。疫苗接种是疾病预防控制的重要方法。现就鼠疫疫苗的研究进展作一综述，为新疫苗的研制提供参考。     

Design,synthesis and biological evaluation of ring A modified 11-keto-boswellic acid derivatives as Pin1 inhibitors with remarkable anti-prostate cancer activity

Pin1 (Protein interaction with never in mitosis A1) is a validated molecular target for anticancer drug discovery. Herein, we reported the design, synthesis, and structure-activity relationship study of novel ring A modified AKBA (3-acetyl-11-keto-boswellic acid) derivatives as Pin1 inhibitors. Most compounds showed superior Pin1 inhibitory activities to AKBA. One of the most promising compounds, 10a, potently inhibited Pin1 with IC₅₀ value of 0.46?μM, while it displayed excellent anti-proliferative effect against prostate cancer cells PC-3 with GI₅₀ value of 1.82?μM. Structure-activity relationship indicated that reasonable structural modifications in ring A had significant impact on improving activity. Further mechanism research revealed that 10a decreased the level of Cyclin D1 and caused cell cycle arrest at G0/G1 phase in PC-3 cancer cells. Thus, compound 10a may serve as potential anti-prostate cancer agent for further investigation through Pin1 inhibition.     

Crocetin treatment inhibits proliferation of colon cancer cells through down-regulation of genes involved in the inflammation

Background

The current study was designed to investigate the effect of crocetin on the proliferation inhibition of colon cancer cells and the underlying mechanism.