Antineuroinflammatory\nPotential of Uvaol Transformation\nProducts by Three Fungal Species

The prevalence of neurodegenerative diseases has increased\nin recent\ndecades. Its exact pathogenesis is not yet fully understood, and only\na few drugs can be used clinically to alleviate disease symptoms.\nIncreasing evidence highlights plant-derived compounds are becoming\na promising resource for mitigating the onset and progression of neurodegenerative\ndiseases. Uvaol (<b>1</b>) is an ursane-type triterpenoid commonly\nfound in olive leaves, fruits, and virgin olive oil. It is one of\nthe rare compounds in olive oil that can penetrate the blood–brain\nbarrier. Despite its potential neuroprotective activity, research\non its structural variations and antineuroinflammatory properties\nremains sparse. This study explored the biotransformation of uvaol\nusing three fungal species: Actinomucor elegans, Aspergillus flavus, and Circinella muscae. This process yielded 15 new compounds\nalong with seven known ones. Their structures were determined through\ncomprehensive spectroscopic analysis. Furthermore, the antineuroinflammatory\nactivities of compounds were evaluated by using MTT and Griess assays.\nNotably, compound <b>9</b> was found to markedly suppress the\ntranscriptional levels of inflammation-associated elements such as\nTNF-α, IL-1β, IL-6, iNOS, and COX-2 in BV-2 cells stimulated\nby lipopolysaccharides (LPS). Moreover, compound <b>9</b> also\nfacilitated autophagy by upregulating ULK1 mRNA expression and downregulating\nthe p62 protein. These results suggested that biotransformation was\nan effective approach for rapidly diversifying uvaol and providing\na basal material for the discovery of candidates in treating neurodegenerative\ndiseases.