Fungal Coculture of <i>Herpotrichia</i> sp. and <i>Trametes versicolor</i> Induces Production of Diverse Metabolites with Anti-Parkinson’s Neuroprotective Activity

Co-cultivation of isopod-associated fungi <i>Herpotrichia</i> sp. SF09 and <i>Trametes versicolor</i> SF09A led to the reciprocal induction of thirteen new compounds (<b>1</b>-<b>7</b> and <b>9</b>-<b>13</b>) with diverse architectures. Importantly, compounds <b>1</b> and <b>2</b> are rare fungal sesquiterpene-saccharide hybrids incorporating a xylopyranose moiety, compound (±)-<b>3</b> represents the first example of a natural linear sesquiterpene racemate, and compound <b>7</b> is a rare α-pyrone derivative with a xylopyranose motif. Their structures were elucidated by analysis of NMR and mass spectrometry data, and their absolute configurations were determined by Mosher's method, microscale derivatization, and single-crystal X-ray diffraction, as well as ECD calculations. All the isolated compounds ameliorated MPP⁺-induced oxidative damage in PC12 cells in a dose-dependent fashion. Among them, compounds <b>5</b> and <b>15</b> showed significant protective action against neuronal injury by MPP⁺ at 5 μM. Meanwhile, transcriptome sequencing was performed to evaluate the molecular mechanism of the neuroprotective activity for compound <b>5</b>. Results indicated that compound <b>5</b> might mitigate MPP⁺-induced neuronal injury through the regulation of multiple signaling pathways, including the PI3K-Akt and MAPK pathways. Our findings suggested that compound <b>5</b> could be a promising neuroprotective agent for the treatment of Parkinson's disease.