Cassane diterpenoid ameliorates dextran sulfate sodium-induced experimental colitis by regulating gut microbiota and suppressing tryptophan metabolism

Ulcerative colitis (UC) is one form of inflammatory bowel disease (IBD), characterized by chronic relapsing intestinal inflammation. As increasing morbidity of UC and deficiency of conventional therapies, there is an urgent need for attractive treatment. Cassane diterpenoids, the characteristic chemical constituents of Caesalpinia genus plants, have been studied extensively owing to various and prominent biological activities. This study attempted to investigate the bioactivity of caesaldekarin e (CA), a cassane diterpenoid isolated from C. bonduc in our previous work, on dextran sulfate sodium (DSS)-induced experimental colitis and clarify the function mechanism. The results indicated that CA ameliorated mice colitis by relieving disease symptoms, suppressing inflammatory infiltration and maintaining intestinal barrier integrity. Furthermore, 16S rRNA gene sequencing analysis indicated that CA could improve the gut microbiota imbalance disrupted by DSS and especially restored abundance of Lactobacillus. In addition, untargeted metabolomics analysis suggested that CA regulated metabolism and particularly the tryptophan metabolism by inhibiting the upregulation of indoleamine 2,3-dioxygenase 1 (IDO-1). It also been proved in IFN-gamma induced RAW264.7 cells. Overall, this study suggests that CA exhibits anti-UC effect through restoring gut microbiota and regulating tryptophan metabolism and has the potential to be a treatment option for UC.