Classical drug assays are often confined to single molecules and targeting 
single pathways. However, it is also desirable to investigate the effects of 
complex mixtures on complex systems such as living cells including the natural 
multitude of signalling pathways. Evidence based on herbal medicine has 
motivated us to investigate potential beneficial health effects of Mucor 
racemosus (M rac) extracts. Secondary metabolites of M rac were collected using 
a good-manufacturing process (GMP) approved production line and a validated 
manufacturing process, in order to obtain a stable product termed SyCircue 
(National Drug Code USA: 10424-102). Toxicological studies confirmed that this 
product does not contain mycotoxins and is non-genotoxic. Potential effects on 
inflammatory processes were investigated by treating stimulated cells with M rac 
extracts and the effects were compared to the standard anti-inflammatory drug 
dexamethasone on the levels of the proteome and metabolome. Using 2D-PAGE, 
slight anti-inflammatory effects were observed in primary white blood 
mononuclear cells, which were more pronounced in primary human umbilical vein 
endothelial cells (HUVECs). Proteome profiling based on nLC-MS/MS analysis of 
tryptic digests revealed inhibitory effects of M rac extracts on 
pro-inflammatory cytoplasmic mediators and secreted cytokines and chemokines in 
these endothelial cells. This finding was confirmed using targeted proteomics, 
here treatment of stimulated cells with M rac extracts down-regulated the 
secretion of IL-6, IL-8, CXCL5 and GROA significantly. Finally, the modulating 
effects of M rac on HUVECs were also confirmed on the level of the metabolome. 
Several metabolites displayed significant concentration changes upon treatment 
of inflammatory activated HUVECs with the M rac extract, including spermine and 
lysophosphatidylcholine acyl C18:0 and sphingomyelin C26:1, while the bulk of 
measured metabolites remained unaffected. Interestingly, the effects of M rac 
treatment on lipids were orthogonal to the effect of dexamethasone underlining 
differences in the overall mode of action.