Phytochemical Investigation of Aquilaria agallocha and Identification of a Diarylheptanoid Exhibiting Anti-Tau Aggregation Activity

Agarwood from <i>Aquilaria agallocha</i>, known as chim-hyuang in Korea, is widely distributed throughout Southeast Asia and has traditionally been used to treat asthma, pain, and gastrointestinal disorders. As part of our ongoing efforts to identify bioactive metabolites from natural sources, a phytochemical investigation of the EtOAc fraction of <i>A. agallocha</i> extract led to the isolation and identification of four compounds, <i>N</i>-<i>trans</i>-feruloyltyramine (<b>1</b>), (3<i>R</i>,5<i>R</i>)-octahydrocurcumin (<b>2</b>), 1,7-bis(4-hydroxyphenyl)heptane (<b>3</b>), and <i>trans</i>-caffeoyltyramine (<b>4</b>), via HPLC purification and LC/MS-based analysis. Structural elucidation of the isolated compounds was achieved using NMR spectroscopy, LC/MS, and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). The absolute configuration of compound <b>2</b> was further confirmed by optical rotation and electronic circular dichroism (ECD) analyses. All isolated compounds (<b>1</b>-<b>4</b>) were evaluated for their inhibitory activity against tau protein aggregation. Notably, compound <b>2</b> exhibited a 43.7% reduction in tau aggregation at 20 μM, without cytotoxicity at the same concentration. These findings indicate that phytochemicals from <i>A. agallocha</i>, particularly the diarylheptanoid compound <b>2</b>, hold promise as natural lead candidates for the development of therapeutic agents targeting tau protein aggregation.