Transcriptomic Insights into the Molecular Mechanisms of Indole Analogues from the Periplaneta americana Extract and Their Therapeutic Effects on Ulcerative Colitis

Ulcerative colitis (UC) is an inflammatory disease of the intestinal mucosa, and its incidence is steadily increasing worldwide. As a traditional Chinese medicinal insect, <i>Periplaneta americana</i> has been broadly utilized in clinical practice to treat wound healing. The tryptophan (Trp), tryptamine (Try), and 1,2,3,4-tetrahydrogen-β-carboline-3-carboxylic acid (Thcc) identified from <i>P. americana</i> concentrated ethanol-extract liquid (PACEL) exhibit significant cell proliferation-promoting and anti-inflammatory effects in the treatment of UC, but the mechanism involved remains obscure. Here, a dextran sulfate sodium (DSS)-induced UC mouse model was used to investigate the efficacy of high/low doses of PACEL, Trp, Try, and Thcc. Transcriptome sequencing was employed to detect the gene expression in the mouse intestine. The results showed that high doses of PACEL, Trp, Try, and Thcc could significantly improve weight loss and diarrhea, notably in the PACEL and Trp groups. Transcriptome analysis indicated that statistically changed genes in four treatment groups were specifically enriched in the immune system. Of these, the integrated analysis identified six hub genes (<i>IL1β</i>, <i>CCL4</i>, <i>CXCL5</i>, <i>CXCR2</i>, <i>LCN2</i>, and <i>MMP9</i>) regulated by NF-κB, which were significantly downregulated. This study investigates the molecular mechanisms underlying the UC treatment properties of indole analogues from PACEL, potentially through the inhibition of the NF-κB signaling pathway.