Inosine (IS) is a naturally occurring metabolite of adenosine with potent immunomodulatory effects. This study investigates the immunomodulatory effects of inosine, particularly its ability to inhibit the development of colorectal cancer (CRC) cells CT26 through modulation of macrophage phenotypes. Aside from the already reported effects of inosine on T cells, in this study, in vitro experiments revealed that inosine could modulate macrophage phenotype. The effects of inosine on the M1/M2 macrophage polarization were investigated at the cellular level. Its role in regulating CRC proliferation and migration was further examined. In addition, a CT26 tumor mouse model was established to assess the mechanism of action of inosine by tumor weight measurement, immunohistochemistry, and immunofluorescence. Inosine significantly increased M1 macrophage markers CD86 and iNOS and enhanced the anti-tumor activity of M1 macrophages, effectively inhibiting CRC progression and metastasis potential. In vivo, inosine had significant tumor inhibitory activity. It also significantly reduced the expression of Ki-67 and promoted the polarization of M1 macrophages.

One undescribed fatty glyceride (1), two unreported N-acetyldopamine dimers (2 and 3), and four known structurally diverse N-acetyldopamine dimers were isolated from adult Vespa velutina auraria Smith. Their structures were elucidated based on a comprehensive analysis of spectroscopic data, HRESIMS, and NMR calculations with ML_J_DP4, and the absolute configurations of 2 and 3 were determined via ECD calculations. Regarding their bioactivities, compounds 5 and 6 can inhibit the production of NO. Moreover, compounds 3, 5 and 7 showed stronger antioxidant activity than the positive control (VC) at 14 μg/mL. A network pharmacology study was used to explore the potential bioactive mechanisms. In addition, a docking study of anti-inflammatory and antioxidative compounds was also performed.