Identification of Kellerin as a Bioactive Principle of Ferula assa-foetida with Potential Anti-Angiogenic and Anti-Inflammatory Effects

Ferula assa-foetida L. (Apiaceae) is a plant native to southern Iran and Afghanistan. Its dried resin, called asafoetida, has been used for millennia as a spice and in traditional medicine for various indications [ 1 ]. In particular, its anti-inflammatory effects have gained increasing interest in research. However, the mechanisms of action and molecular targets of these constituents are yet to be fully elucidated. This study investigates the potential anti-angiogenic and anti-inflammatory activities of F. assa-foetida resin and its bioactive constituents. A methanolic extract of the resin inhibited both the proliferation of primary endothelial cells as well as the adhesion of leukocytes to the endothelial cells upon pro-inflammatory activation. Bioassay-guided fractionation identified the dichloromethane fraction as the most potent one, reducing endothelial cell proliferation with an IC 50 of 15 μg/mL. This fraction was further purified, which led to the isolation and structural characterization of three sesquiterpene coumarins: farnesiferol B, farnesiferol C, and kellerin [ 2 ]. Among them, kellerin showed the highest antiproliferative activity with an IC 50 of 6 μM; and significantly reduced leukocyte adhesion at a concentration of 5 μM. Transcriptomic analyses in primary monocytes revealed a downregulation of inflammation-related genes after kellerin treatment. Further computational analysis using decoupleR [ 3 ] predicted the involvement of transcription factors associated with inflammation, including STAT3, FOS and JUN. Ongoing studies, including proteomic analyses, aim to elucidate the underlying molecular mechanisms and identify involved target proteins. Taken together, our work highlights kellerin as a promising bioactive lead compound with dual anti-angiogenic and anti-inflammatory potential warranting further pharmacological research. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany