Project description:Untargeted-metabolomics LC-MS/MS analysis of commercial natural products pool, analyzed with different DDA settings with the objective to find the best one.
Project description:Natural products exhibit potential as candidates for developing multi-target agents for Alzheimer's disease treatment. The aim of this study is to utilize network-based medicine to identify novel natural products for Alzheimer's disease, and investigate their efficacy and mechanisms of action. In this study, we identified (-)-Vestitol and Salviolone as new potential natural products for treating Alzheimer's disease via an Alzheimer's disease-related pathway-gene network. Both natural products improved the cognition of APP/PS1 transgenic mice, reduced Aβ deposition, and lowered soluble toxic Aβ levels in the brain. Notably, a synergistic effect was observed when the two natural products were combined. Transcriptomic analysis and qRT-PCR experiments revealed that the synergistic mechanism of (-)-Vestitol and Salviolone combination is associated with the regulation of a broader range of AD-related pathways and genes, particularly the neuroactive ligand-receptor interaction pathway and calcium signaling pathway.
Project description:Untargeted-metabolomics LC-MS/MS analysis of commercial natural products pool, analyzed with different DDA settings with the objective to find the best one.
Project description:SDF-1 has been reported to trigger ADAMTS4,5 overexpression through activating CXCR4 signaling in chondrocytes. Here we described the transcriptional changes of SDF-1-treatment as well as natural products CXCR4 antagonists treatment.
Project description:We integrated quantitative proteomics and activity-based protein profiling (ABPP) approach to systematically elucidate the involved pathways and the covalent targets of natural products.
Project description:Electrophilic groups, such as Michael acceptors, expoxides, are common motifs in natural products (NPs). Electrophilic NPs can act through covalent modification of cysteinyl thiols on functional proteins, and exhibit potent cytotoxicity and anti-inflammatory/cancer activities. Here we describe a new chemoproteomic strategy, termed multiplexed thiol reactivity profiling (MTRP), and its use in target discovery of electrophilic NPs. We demonstrate the utility of MTRP by identifying cellular targets of gambogic acid, an electrophilic NP that is currently under evaluation in clinical trials as anticancer agent. Moreover, MTRP enables simultaneous comparison of seven structurally diversified -unsaturated -lactones, which provides insights into the relative proteomic reactivity and target preference of diverse structural scaffolds coupled to a common electrophilic motif and reveals various potential druggable targets with liganded cysteines. We anticipate that this new method for thiol reactivity profiling in a multiplexed manner will find broad application in redox biology and drug discovery.