Antineuroinflammatory Potential of Uvaol Transformation Products by Three Fungal Species

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