Recombinant yeast-based screening of plant extracts for protein tyrosine phosphatase 1B inhibitors

Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin and leptin signaling, is a key target in treating metabolic disorders. In this study, a recombinant yeast-based screening system was used to identify plant extracts with potential PTP1B inhibitory activity. Among the 1,178 extracts tested, eight inhibited yeast growth and those exhibiting cytotoxicity were excluded based on the 3T3-L1 cell viability results. P1171, prepared from Ampelopsis brevipedunculata (1 mg/mL), showed 87.8% PTP1B inhibition, which was approximately 17% higher than that induced by vanadate (30 mM). The enzyme kinetics of extract P1171 indicated a noncompetitive inhibition pattern. Additionally, it reduced the expression of peroxisome proliferator-activated receptor gamma by 88% in 3T3-L1 adipocytes compared to the control. Overall, these results highlight P1171 as a promising natural PTP1B inhibitor source. In addition, the recombinant yeast-based system demonstrated its utility for the rapid screening of such candidates.