Mechanism of protein tyrosine phosphatase 1B inhibition by theaflavanoside IV isolated from methanolic extract of tea (Camellia sinensis) seed shells.

Camellia sinensis (tea) seeds have been identified as potential sources of nutraceutical compounds. In this study, caffeine and theaflavanoside IV were annotated as the most abundant phytochemicals in the seed shells of C. sinensis. Both compound displayed potent inhibitions against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 37.9 ± 3.5 and 8.7 ± 1.1 µM, respectively. In the kinetic study, caffeine inhibited PTP1B with mixed type I mode, which prefers to bind to free enzyme. Theaflavanoside IV showed competitive and reversible simple slow-binding inhibition [k3 = 0.1 µM-1·min-1, k4 = 0.002 min-1, Kiapp = 0.0002 µM]. This is the first report on PTP1B-inhibitory activity of these compounds and their action mechanisms. These results suggest their potential in the development of antidiabetic agents.

Bakkenolides and Caffeoylquinic Acids from the Aerial Portion of Petasites japonicus and Their Bacterial Neuraminidase Inhibition Ability.

Petasites japonicus have been used since a long time in folk medicine to treat diseases including plague, pestilential fever, allergy, and inflammation in East Asia and European countries. Bioactive compounds that may prevent and treat infectious diseases are identified based on their ability to inhibit bacterial neuraminidase (NA). We aimed to isolate and identify bioactive compounds from leaves and stems of P. japonicas (PJA) and elucidate their mechanisms of NA inhibition. Key bioactive compounds of PJA responsible for NA inhibition were isolated using column chromatography, their chemical structures revealed using 1 H NMR, 13 C NMR, DEPT, and HMBC, and identified to be bakkenolide B (1), bakkenolide D (2), 1,5-di-O-caffeoylquinic acid (3), and 5-O-caffeoylquinic acid (4). Of these, 3 exhibited the most potent NA inhibitory activity (IC50 = 2.3 ± 0.4 µM). Enzyme kinetic studies revealed that 3 and 4 were competitive inhibitors, whereas 2 exhibited non-competitive inhibition. Furthermore, a molecular docking simulation revealed the binding affinity of these compounds to NA and their mechanism of inhibition. Negative-binding energies indicated high proximity of these compounds to the active site and allosteric sites of NA. Therefore, PJA has the potential to be further developed as an antibacterial agent for use against diseases associated with NA.