Lanostane-type triterpenoids from ethnomedicinal fungi inhibit endothelial cell proliferation

Ethnomedicinal fungi have a long history of use in the treatment of tumors and inflammatory disorders, pathologies often associated with dysregulated angiogenesis and immune-vascular interactions. However, their effects on endothelial cell functions relevant to angiogenesis and inflammation remain insufficiently characterized.

The aim of this study was to identify the bioactive compounds from ethnopharmacologically relevant medicinal fungi by screening their ethanolic extracts for their effects on angiogenesis- and inflammation-related endothelial cell functions, followed by the identification and targeted isolation of these compounds using molecular networking and bioactivity-guided fractionation.

Twenty-six ethanolic extracts from traditionally and popularly used macrofungi were screened in vitro for bioactivities related to angiogenesis and inflammation. Assays included endothelial cell proliferation and migration using human umbilical vein endothelial cells (HUVECs), as well as leukocyte adhesion to TNF-activated endothelial cells. Feature-based molecular networking was applied to correlate bioactivity with chemical profiles. Bioactive constituents from Inonotus obliquus were isolated and evaluated for anti-proliferative activity.

In the three assays performed, the inhibition of endothelial cell proliferation was observed as the most consistent and robust effect. Eleven fungal extracts significantly inhibited HUVEC proliferation at 25 μg/mL, with Fomitopsis betulina and Inonotus obliquus showing the highest activity. None of the extracts affected endothelial migration, and only one inhibited leukocyte adhesion. Molecular networking revealed a rich and diverse occurrence of lanostane-type triterpenes (LTTs) in all anti-proliferative extracts. Chemical investigation of Inonotus obliquus led to the isolation of several LTTs, of which lanosterol and inotodiol inhibited HUVEC proliferation with IC₅₀ values of 2.1 μM and 9.1 μM, respectively, whereas more oxidized LTTs showed reduced activity.

Many extracts enriched in LTTs exhibit pronounced anti-proliferative effects on endothelial cells, suggesting a potential modulation of angiogenesis-related processes and thereby supporting the traditional use of certain polypores in conditions involving aberrant angiogenesis.