Integrated Proteomics and Metabolomics Link Acne to the Action Mechanisms of Cryptotanshinone Intervention

The label-free methods of proteomic combined with metabolomics were applied to explore the mechanisms of Cryptotanshinone (CPT) intervention in rats with acne. The model group consisted of rats given oleic acid (MC), then treated with CPT, while control groups did not receive treatment. The skin samples were significantly different between control, model and CPT-treated groups in hierarchical clustering dendrogram. Obvious separations of the skin metabolic profiles from the three groups were found through PCA scoring. In total, 231 and 189 differentially expressed proteins (DEPs) were identified in MC and CPT groups, respectively. By the KEGG analysis, five protein and metabolite pathways were found to be significantly altered. These played important roles in response to oleic acid-induced acne and drug treatment. CPT could negatively regulate glycolysis/gluconeogenesis and histidine metabolisms to decrease keratinocyte differentiation and improve excessive keratinization and cellular barrier function. CPT could down-regulate the IL-17 signaling pathway and regulate the acne-driven immune response of sebum cells. The biosynthesis of unsaturated fatty acids metabolism, glycerophospholipid metabolism and linoleic acid pathways could significantly alter sebum production and control sebaceous gland secretion after CPT treatment. The gap junction was up-regulated after CPT treatment and the skin barrier turned back to normal. Krt 14, Krt 16 and Krt 17 were significantly down-regulated, decreasing keratinization, while inflammatory cell infiltration was improved by down-regulation of Msn, up-regulation of linoleic acid and estrogen pathways after CPT treatment. These results propose action mechanisms for the use of CPT in acne, as a safe and potential new drug.