A Novel Phenolic From the Heartwood of Cotinus coggygria Scop. With Potential Neuroprotective Effects: In Silico and In Vitro Studies

Seven known phenolic compounds ( 2 – 8 ) along with one new phenolic compound ( 1 ) were isolated from the heartwood of Cotinus coggygria Scop. (Anacardiaceae). Among them, compounds 3 – 5 are reported from the genus Cotinus for the first time, while compounds 2 and 6 – 8 are reported from the family Anacardiaceae for the first time. The structure of the new compound was elucidated by detailed spectroscopic analysis, including HR‐ESI‐MS, 1D, and 2D NMR experiments. In vitro assays showed that compound 1 attenuated glutamate‐induced oxidative injury in HT22 cells (EC 50 = 3.852 µM, MTS assay) and inhibited TNF‐α‐induced NF‑κB activation in 293T luciferase reporter cells. Molecular docking suggested that compound 1 may bind to IKKβ, consistent with the observed NF‑κB inhibition. Preliminary structure‐activity relationship trend analysis indicated that compounds possessing a 6″‐ O ‐rhamnose‐containing disaccharide moiety ( 6 – 8 ) showed stronger apparent protective activity than the 6″‐ O ‐galloyl derivatives ( 1 – 5 ) under the present assay conditions. These preliminary findings suggest that cotinusin A ( 1 ) may warrant further investigation for its potential against glutamate‐induced oxidative neuronal injury. However, whether the observed NF‑κB inhibitory activity translates into anti‐neuroinflammatory effects in relevant models remains to be determined, and further mechanistic and in vivo studies are needed to establish its therapeutic potential.