Eriodictyon californicum Extract Inhibits Therapeutically Relevant Protein Tyrosine Phosphatase 1B

Protein tyrosine phosphatase 1B (PTP1B) is a therapeutic target for diabetes, obesity, and cancers. Despite several promising inhibitors, none have progressed to the clinic, emphasizing the need for continued identification of novel inhibitors. This study demonstrates the potential of Eriodictyon californicum ethanolic leaf extract (ECE) as a source of PTP1B inhibitors. Through in vitro assays, we observed a strong, dose-dependent inhibition of PTP1B by ECE, ranging from 21.3 ± 8.7% at 1.3 µg/ml to 101.8 ± 1.9% at 50 µg/ml with an IC₅₀ of 4.19 µg/ml. Preliminary kinetic analysis revealed an apparent mixed inhibition, with changes in both V_max and K_m values. Molecular docking of known bioactive compounds in the plant showed modest binding energies. Most compounds, particularly flavonones, are predicted to bind to the catalytic site of PTP1B, exhibiting potential hydrogen bonding and hydrophobic interactions with critical active site residues. This study is the first to demonstrate the inhibitory potential of ECE against PTP1B, positioning E. californicum as a promising source of PTP1B inhibitors, further expanding the role of nature-based therapies for diseases associated with PTP1B dysregulation.