Although the biological processes of organism under hypoxic stress had been elucidated, the whole physiological changes of Saccharomyces cerevisiae are still unclear. In this work, we investigated the changes of biological process of S. cerevisiae under hypoxia by the methods of transcriptomics, proteomics, metabolomics, and bioinformatics. The results showed that the expression of a total of 1017 mRNA in transcriptome, 213 proteins in proteome, and 51 metabolites in metabolome had been significantly changed between the hypoxia and normoxia conditions. Moreover, based on the integration of system-omics data, we found that the carbohydrate, amino acids, fatty acid biosynthesis, lipid metabolic pathway, and oxidative phosphorylation were significantly changed in hypoxic stress. Among these pathways, the glycerophospholipid metabolic pathway was remarkably up-regulated from the mRNA, protein, and metabolites levels under hypoxic stress, and the expression of relevant mRNA was also confirmed by the qPCR. The metabolites of glycerophospholipid pathway such as phosphatidylcholine, phosphatidylethanolamine, phosphoinositide, and phosphatidic acids probably maintained the stability of cell membranes against hypoxic stress to relieve the cell injury, and kept S. cerevisiae survive with energy production. These findings in the hypoxic omics and integrated networks provide very useful information for further exploring the molecular mechanism of hypoxic stress.

Angiogenesis is a key step for tumour growth and metastasis, and anti-angiogenesis has been proposed as an important strategy for cancer therapy. Tryptanthrin is a weakly basic alkaloid isolated from the dried roots of medicinal indigo plants and has been shown to possess anti-tumour activities on various cancer cell types. This study aims to investigate the in vitro and in vivo anti-angiogenic activities of tryptanthrin and to unravel its underlying molecular action mechanisms. Our results show that tryptanthrin inhibited the in vitro proliferation, migration, and tube formation of the human microvascular endothelial cells (HMEC-1) in a concentration-dependent manner and significantly suppressed angiogenesis in Matrigel plugs in mice. Mechanistic studies indicated that tryptanthrin reduced the expression of several pro-angiogenic factors (Ang-1, PDGFB and MMP2). Tryptanthrin was also found to suppress the VEGFR2-mediated ERK1/2 signalling pathway in HMEC-1 cells and molecular docking simulation indicated that tryptanthrin could bound to the ATP-binding site of VEGFR2. Collectively, the present study demonstrated that tryptanthrin exhibited both in vitro and in vivo anti-angiogenic activities by targeting the VEGFR2-mediated ERK1/2 signalling pathway and might have therapeutic potential for the treatment of angiogenesis-related diseases.

Danshen, the dried root and rhizome of Salvia miltiorrhiza Bunge, is a widely used medicinal plant for the treatment of cardiovascular diseases in China and a complementary medicine in the West. Danshen is indexed in the 2010 Chinese Pharmacopoeia , with more than 35 formulations and concoctions containing Danshen water-extracts, ethanolic extracts or their combination, which are rich in phenolic acids and different levels of tanshinones. There are rare reports on the adverse effects of Danshen preparations. It is, however, well-known that Danshen leads the anticoagulation failure of warfarin. The Danshen-warfarin interaction may be mediated via both pharmacodynamic and pharmacokinetic mechanisms. This review does not summarize recent progress, but the effects of Danshen and its active ingredients on the interactions of cytochrome P450 (CYP450) and drug transporters, as well as the analysis of ingredients, and the metabolism and pharmacokinetics that are related to these interactions. Tanshinones play significant roles in the inhibition and induction of several CYP450 isozymes. It can be concluded that precautions should be taken when using Danshen preparations rich in tanshinones for CYP-related herb-drug interactions.