Isolation and Characterization of Secondary Metabolites from Hydractinia-Associated Fungus, Penicillium brevicompactum MSW10-1, and Their Inhibitory Effects on Hepatic Lipogenesis

Marine organism-associated microbes are an important source of structurally diverse and biologically active secondary metabolites exhibiting antimicrobial, anticancer, and anti-inflammatory activities. In this study, we investigated <i>Penicillium brevicompactum</i> MSW10-1, isolated from <i>Hydractinia echinata</i>, a marine invertebrate adapted to extreme intertidal and subtidal environments with variable temperature, salinity, and oxygen conditions. Through a combination of LC/MS-guided chemical analysis and chromatographic purification, eight secondary metabolites were isolated, including brevicolactones A (<b>1</b>) and B (<b>2</b>). The absolute chemical structures of <b>1</b> and <b>2</b> were determined based on NMR spectroscopic experiments, HR-ESIMS data, and quantum chemical ECD calculations. The isolated compounds (<b>1</b>-<b>8</b>) were evaluated for their ability to inhibit hepatic lipogenesis, a key process in lipid metabolism that is dysregulated in metabolic-dysfunction-associated steatotic liver disease. Furthermore, the inhibitory effects of the isolated compounds on lipid accumulation were further evaluated in primary mouse hepatocytes, using Oil Red O staining. These findings suggested that the isolated compounds may serve as promising candidates for the treatment of metabolic liver diseases associated with lipid dysregulation.