Isoschaftoside in Fig Leaf Tea Alleviates Nonalcoholic Fatty Liver Disease in Mice via the Regulation of Macrophage Polarity.

Background: Nonalcoholic fatty liver disease (NAFLD) is a subset of fatty liver disease that is not caused by alcohol or viruses, and its increasing incidence presents a major global health concern. As few pharmacotherapies are available for NAFLD, lifestyle modifications, including diet and exercise, serve as the foundation for treatment. Therefore, NAFLD prevention is more important than cure, emphasizing the need for drugs with excellent safety and long-term efficacy. Fig leaf tea contains rutin and isoschaftoside (ISS), which may possess anti-inflammatory properties. Therefore, the aim of this murine-model-based study was to investigate the potential benefits of fig leaf tea in alleviating NAFLD and to determine the underlying mechanism by gene expression analysis.

Results: We found that in mice with NAFLD induced by a high-fat diet, the administration of high concentration fig leaf tea or 50 µM ISS significantly ameliorated lobule inflammation. In contrast, low concentration fig leaf tea containing 75 µM ISS did not improve inflammation. The balance between the NAFLD-promoting component of fig leaf tea and the inhibitory effect of ISS was thought to be affected. Gene expression analysis of the liver showed that high concentration fig leaf tea or ISS significantly suppressed the expression of M1 macrophage markers such as CD antigens, toll-like receptors (TLR), chemokines, and cytokines. Further, ISS suppressed the amount of TNF-α released during the M1 polarization of macrophage cells upon lipopolysaccharide (LPS) stimulation.

Conclusions: Overall, these results suggest that controlling macrophage polarization may improve NAFLD. Furthermore, these findings highlight the potential clinical applicability of ISS.