Xanthine oxidase (XO) is an important target for the treatment of hyperuricemia (HUA), which mediates the production of uric acid (UA). The mechanism of action between flavonoids and XO in cell biology and structural bioinformatics has not been fully explored. In this study, 160 flavonoids were extensively screened and evaluated for their XO inhibitory activity in vitro. Molecular docking and molecular dynamics (MD) simulation were further used to explore the interaction mechanism between flavonoids and XO. The diosmetin, luteolin, and kaempferol were innovatively found to inhibit the UA production of AML12 cells in a time-and dose-dependent manner, in which the IC 50 is 6.56, 8.92, and 10.46 μM, respectively. Combined with the MD simulations of the complexes of flavonoids and XO, results showed that flavonoids bind the Mo-molybdopterin domain of XO mainly through hydrogen bonding and hydrophobicity. Lys772 and Thr1011 were the key sites to enhance the inhibitory activity of XO.
Cu4Ti2O/TiO2/diatomite with double interface Cu4Ti2O/TiO2 and rutile/anatase heterojunction were fabricated, which demonstrated good antibacterial activity (100%) against Acinetobacter baumannii. Cu/TiO2/diatomite prepared under optimum preparation conditions (added diatomite, 0.005 g; Cu, 0.005 g; reaction temperature, 180 °C; reaction time, 8 h) exhibited high antibacterial activity (100%) against A. baumannii. For the Cu/TiO2/diatomite powders, their structural, compositional, optical and morphological traits were characterized by XRD, SEM, TEM, XPS, BET, FTIR, Mapping, and DRS. It was shown that Cu/TiO2/diatomite under optimum conditions consisted of the double interface Cu4Ti2O/TiO2 and rutile/anatase heterojunction with the narrowest band gap and largest BET surface area, pore size, and pore volume. Then, it could exhibit the best photocatalytic activity.
Ginkgo biloba, as a medicinal plant
in both traditional
and western medicine, emerged as a potential therapeutic agent for
the management of a variety of diseases, but ginkgo biflavones (bilobetin,
isoginkgetin, and ginkgetin) application in cancer therapy and underlying
mechanisms of action remained elusive. In the present study, we identified
ginkgo biflavones as potential p53 activators that could enhance p53
protein expression level by inhibiting MDM2 protein expression. At
the same time, they induced cell death independent of p53 transcriptional
activity. Moreover, ginkgetin was a standout among ginkgo biflavones
that reduced the survival of HCT-116 cells by induction of apoptosis
and G2/M phase arrest. Furthermore, ginkgo biflavones induced ROS
generation significantly, which resulted in ferroptosis. Finally,
we provide evidence that ginkgetin strengthened the antitumor effect
of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model.
To sum up, ginkgo biflavones represent a new class of p53 activator
that depends on the p53 wild-type status and warrants further exploration
as potential anticancer agents.
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