Chemoproteomics reveals Sofalcone inhibits the inflammatory response of Caco-2 cells by covalently targeting HMGB1.

Sofalcone (Sof), a synthetic analog of sophoradin, is a type of natural phenol derived from the traditional medicinal herb Sophora subprostrata, with potent anti-inflammatory activity. However, the mechanisms of action of Sof for treating intestinal-associated inflammation are not well known. In this work, we identified high mobility group box 1 (HMGB1) as the key covalent target of Sof for the anti-inflammatory activity in the human colonic epithelial cells through quantitative chemoproteomics profiling.

Oridonin acts as a novel senolytic by targeting glutathione S-transferases to activate the ROS-p38 signaling axis in senescent cells.

Most of the known senolytics are anti-cancer drugs or their derivative molecules. However, senolytics derived from the active ingredients of traditional Chinese medicine (TCM) are rarely reported. Here, we identified oridonin as a novel senolytic and further revealed that it might target a class of glutathione S-transferases to activate ROS-p38 signaling and induce apoptosis in senescent cells.