Secondary Metabolites Produced by the Dominant Fungus <i>Eurotium cristatum</i> in Liupao Tea and Their Hypolipidemic Activities by Regulating Liver Lipid Metabolism and Remodeling Gut Microbiota

Liupao tea is a postfermented dark tea with hypolipidemic activity. Research on the active substances in Liupao tea has primarily focused on those derived from the tea itself, overlooking the secondary metabolites produced by its predominant fungus, <i>Euirotium cristatum</i>. In this study, <i>E. cristatum</i> CPCC 401251, the predominant strain found in Liupao tea under investigation, was isolated and analyzed. A total of 19 representative metabolites, including prenylbenzaldehydes, diketopiperazines, and anthraquinones, were obtained from its culture. Subsequent analysis revealed the presence of multiple secondary metabolites of <i>E. cristatum</i> CPCC 401251 in Liupao tea. The 19 compounds significantly reduced the lipid content in free fatty acid (FFA)-stimulated hepatocyte AML-12 cells to varying degrees. Considering the content, chemical class, and biological activity of secondary metabolites from <i>E. cristatum</i> CPCC 401251, compounds <b>1</b>, <b>7</b>, and <b>13</b> were selected to detect their hypolipidemic activities and potential mechanisms in hyperlipidemia golden hamsters. Compound <b>1</b> exerted a hypolipidemic effect by activating the AMPK signaling pathway, decreasing <i>Scd1,</i> and improving intestinal flora. Compounds <b>7</b> and <b>13</b> played a role in the hypolipidemic activity by regulating the gene expression related to lipid synthesis and degradation, including upregulating the mRNA levels of <i>Ppar</i>α, <i>Hsl</i>, and <i>Atgl</i>, and decreasing the mRNA level of <i>Scd1</i>. These findings help us understand the dominant fungus <i>E. cristatum</i> secondary metabolites presenting in Liupao tea and their potential hypolipidemic contributions. This work improves the understanding of the active substances in Liupao tea and highlights the health-promoting effects of microorganisms in the fermented tea.