C-geranylated flavonoids from Paulownia tomentosa Steud. fruit as potential anti-inflammatory agents

Paulownia tomentosa Steud., a traditional Chinese medicinal plant, was used for many centuries in Chinese herbal medicine as a component of remedies for many illnesses, including inflammatory diseases. It is a rich source of phenolic compounds, mainly geranylated flavonoids, which are currently studied for their promising biological activities.

The study aimed to isolate minor geranylated flavanones and flavones from P. tomentosa fruit and evaluate their cytotoxicity and possible anti-inflammatory effects in a cell-based model of inflammation.

Chromatographic separation of chloroform portion of the ethanolic extract of P. tomentosa fruit led to the isolation of twenty-seven flavonoids (1-27), twenty-six of them geranylated with different modifications and one non-geranylated flavanone, and two phenolic compounds. Compounds were identified using UV, IR, HRMS, NMR, and CD spectroscopy. Ten of these compounds (7-10, 12, 21, 22, 24, 25, and 27) were determined to be new flavonoid derivatives obtained from a natural source for the first time. Selected compounds were analyzed for cytotoxicity and anti-inflammatory potential to affect the activation of nuclear factor κB/activator protein 1 (NF-κB/AP-1) after lipopolysaccharide (LPS) stimulation.

All the test compounds (1-21 and 23-26) reduced the activation of NF-κB/AP-1 24 h after the addition of LPS. Eight compounds (5, 14-18, 21, and 26) were more active than prednisone, a widely used anti-inflammatory drug. However, this effect was not seen significantly on the level of TNF-α and IL-1β, which can be explained by the plurality of possible outcomes of activation of the NF-κB pathway in cells.

Results of the presented study confirmed that constituents from traditional Chinese medicinal plant P. tomentosa Steud. have promising anti-inflammatory activities and can serve as a potential source of inspiration for new anti-inflammatory medications.