LC-MS-based proteomics: insights into natural product-directed cellular targeting

Natural products (NPs) have historically served as sources of bioactive molecules with considerable clinical therapeutic potential. Their complex molecular mechanisms can be investigated through in vitro proteomics utilizing liquid chromatography (LC)-mass spectrometry (MS) and related techniques. In this review, we provide a framework for exploring protein-level alterations caused by NPs using both top-down and bottom-up proteomic methods. We comprehensively explore the importance of various components, including instrument selection, cell/tissue treatment, protein extraction, digestion, and strategies, and also highlight the significance of both label-free and label-based quantification, bioinformatics techniques, and data standardization processes. In addition, we discuss several case studies in which LC-MS-based proteomics has been used to provide a thorough understanding of cellular pathways affected by NPs, providing crucial insights for drug discovery and therapeutic strategies.