ABSTRACT
Type 2 diabetes mellitus (T2DM) stands as a prevalent global public health issue caused by deficiencies in the action of insulin and/or insulin production. In the liver, insulin plays an important role by inhibiting hepatic glucose production and stimulating glycogen storage, thereby contributing to blood glucose regulation. Kaempferitrin (KP) and kaempferol (KM), flavonoids found in Bauhinia forficata, exhibit insulin-mimetic properties, showing promise in managing T2DM. In this study, we aimed to assess the potential of these compounds in modulating the insulin signaling pathway and/or glucose metabolism. Cell viability assays confirmed the non-cytotoxic nature of both compounds toward HepG2 cells at the concentrations and times evaluated. Theoretical molecular docking studies revealed that KM had the best docking pose with the IR ß subunit when compared to the KP. Moreover, Langmuir monolayer evaluation indicated molecular incorporation for both KM and KP. Specifically, KM exhibited the capability to increase AKT phosphorylation, a key kinase in insulin signaling, regardless of insulin receptor (IR) activation. Notably, KM showed an additional synergistic effect with insulin in activating AKT. In conclusion, our findings suggest the potential of KM as a promising compound for stimulating AKT activation, thereby influencing energy metabolism in T2DM.
ABSTRACT
Some biological properties of violacein are believed to be associated with their interactions with lipid surfaces, encouraging research on the identification of membrane sites capable of drug binding. In this study, we investigated the interaction of violacein with cell membrane models represented by Langmuir monolayers of selected lipids: one representing healthy cellular membranes: dipalmitoylphosphatidylcholine, DPPC, and the other one representing tumorigenic cellular membranes, dipalmitoylphosphatidylserine, DPPS. It is shown that even small amounts of the compound affect the surface pressure-area isotherms as well as the surface vibrational spectra of the lipid monolayers, which points to a significant interaction. Such effects depend on the electrical charge of the monolayer-forming molecules, with the drug activity being particularly distinctive for negatively charged lipids in relation to zwitterionic lipids. Morphological analysis also suggests that violacein at the air-water interface is homogenized when incorporated in both lipids. Although the interaction of violacein with the lipids affects viscoelastic and structural properties of the Langmuir monolayer, it is not present permeability through lipid bilayers, as investigated using liposomes. These results therefore may have important implications in understanding how violacein acts on specific sites of the cellular membrane, and evidence the fact that the lipid composition of the monolayer modulates the interaction with the lipophilic drug.
