Application of LC-MS based glutathione-trapped reactive metabolites in the discovery of toxicity of traditional Chinese medicine

We summarized the discovery of liquid chromatography mass spectrometry （LC-MS） based glutathione （GSH） capture of reactive metabolites in traditional Chinese medicine （TCM）, which provides scientific basis for further research and clinical application of Chinese medicine toxicity discovery. This dissertation overviews relevant literatures of GSH capture of reactive metabolites in recent years. And then we review the principles and methods of LC-MS based GSH capture of reactive metabolites, as well as the research progress in the discovery of toxicity of TCM including pyrrolizidine alkaloids, furans and quinoid species. The review shows that the representative compounds of TCM includes adonifoline, lasiocarpine, diosbulbin B and safrol are well dctected by LC-MS based GSH capture technique. And the main analytic systems of LC-MS are triple quadrupole and Q-Trap mass spectrometer. Constant neutral loss scan （CNLS）, precursor ion scan （PIS） and multiple reaction monitor （MRM） are main detection methods to monitor the characteristic GSH conjugate fragmentations. The approach of LC-MS based GSH-trapped metabolites has a good application prospect in the discovery of toxic components of TCM.

Curcumin and Apigenin – novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease

Alzheimer’s disease is a progressive neurodegenerative disorder, characterized by deposition of amyloid beta, neurofibrillary tangles, astrogliosis and microgliosis, leading to neuronal dysfunction and loss in the brain. Current treatments for Alzheimer’s disease primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for Alzheimer’s disease patients. This review will provide an overview of the proven antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of curcumin and apigenin and discuss the potential of these compounds for Alzheimer’s disease prevention and treatment. We suggest that these compounds might delay the onset of Alzheimer’s disease or slow down its progression, and they should enter clinical trials as soon as possible.

Protein target discovery of drug and its reactive intermediate metabolite by using proteomic strategy

Identifying protein targets of bioactive compounds is an effective approach to discover unknown protein functions,identify molecular mechanisms of drug action,and obtain information for optimization of lead compounds.At the same time,metabolic activation of a drug can lead to cytotoxicities.Therefore,it is very important to systemically characterize the drug and its reactive intermediate.Mass spectrometry-based proteomic approach has emerged as the most efficient to study protein functions and modifications.This review will discuss method development for the drug target discovery and the application in different fields including the drug toxicity mechanism caused by reactive metabolites.

LC–MS-based metabolomics in profiling of drug metabolism and bioactivation

Since metabolism significantly affects drug safety and efficacy,determining the metabolic profile of a drug is a critical part of drug development.The application of an LC–MS-based metabolomic approach has gained more widespread use in identifying drug metabolites,developing metabolic maps and lending clues to mechanisms of bioactivation.Thus,the LC–MS-based metabolomic approach is a powerful tool for profiling of drug metabolism and bioactivation.