RNA-seq analysis reveals modulation of inflammatory pathways by an enriched-triterpene natural extract in mouse and human macrophage cell lines
Chronic Inflammation has a key role in the development of insulin resistance and type 2 diabetes. Previously, we demonstrated that OBE100, a natural extract from the leaves of Eucalyptus tereticornis, has anti-inflammatory properties. Three pentacyclic triterpenoids, ursolic acid, oleanolic acid, and ursolic acid lactone are the major compounds present in OBE100. These molecules have shown multiple biological activities. In this study we analyzed how the compounds of OBE100 modify macrophage gene expression using RNA sequencing. Triterpenoids regulate the inflammatory program in activated macrophages inhibiting the expression of many cytokines, chemokines, and inflammatory mediators. However, the OBE100 extract has a more powerful immunomodulatory effect than the triterpene mixture increasing the number of genes regulated, both in mouse and human models. Our study shows that OBE100 is a promising extract for the treatment of diabetes that can break the link between inflammation and insulin resistance. Overall design: To establish the effect and molecular mechanisms of the OBE100 extract, we bought J774A.1 (TIB-67™) mouse monocyte; macrophage cells and U-937 (CRL-1593.2) human monocytic (pre-macrophage line), we differentiated them to macrophages using 100 nM phorbol myristate acetate (PMA), and  we treated the samples with Crude extract OBE100, M1 (mixture of UA, OA and UAL), UA, OA, and UAL We then performed RNA seq profiling using data obtained from RNA-seq. We compared activated macrophages againts each control (OBE100, M1, UA, OA, UAL) and we also included a monocyte control, to verify that the activation to macrophage was successfull