“…Diabetes mellitus (DM) has risen quickly in recent decades and currently, over 415 million DM sufferers worldwide, predicted to hit 642 million by 2040 [1]. Moreover, the incidence of DM in younger people, even before puberty, is rising, including some obese children [2,3].…”
As a traditional medicine, Angelica decursiva has been used for the treatment of many diseases. The goal of this study was to evaluate the potential of four natural major dihydroxanthyletin-type coumarins—(+)-trans-decursidinol, Pd-C-I, Pd-C-II, and Pd-C-III—to inhibit the enzymes, protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. In the kinetic study of the PTP1B enzyme’s inhibition, we found that (+)-trans-decursidinol, Pd-C-I, and Pd-C-II led to competitive inhibition, while Pd-C-III displayed mixed-type inhibition. Moreover, (+)-trans-decursidinol exhibited competitive-type, and Pd-C-I and Pd-C-II mixed-type, while Pd-C-III showed non-competitive type inhibition of α-glucosidase. Docking simulations of these coumarins showed negative binding energies and a similar proximity to residues in the PTP1B and α-glucosidase binding pocket, which means they are closely connected and strongly binding with the active enzyme site. In addition, dihydroxanthyletin-type coumarins are up to 40 µM non-toxic in HepG2 cells and have substantially increased glucose uptake and decreased expression of PTP1B in insulin-resistant HepG2 cells. Further, coumarins inhibited ONOO−-mediated albumin nitration and scavenged peroxynitrite (ONOO−), and reactive oxygen species (ROS). Our overall findings showed that dihydroxanthyletin-type coumarins derived from A. decursiva is used as a dual inhibitor for enzymes, such as PTP1B and α-glucosidase, as well as for insulin susceptibility.
“…Diabetes mellitus (DM) has risen quickly in recent decades and currently, over 415 million DM sufferers worldwide, predicted to hit 642 million by 2040 [1]. Moreover, the incidence of DM in younger people, even before puberty, is rising, including some obese children [2,3].…”
As a traditional medicine, Angelica decursiva has been used for the treatment of many diseases. The goal of this study was to evaluate the potential of four natural major dihydroxanthyletin-type coumarins—(+)-trans-decursidinol, Pd-C-I, Pd-C-II, and Pd-C-III—to inhibit the enzymes, protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. In the kinetic study of the PTP1B enzyme’s inhibition, we found that (+)-trans-decursidinol, Pd-C-I, and Pd-C-II led to competitive inhibition, while Pd-C-III displayed mixed-type inhibition. Moreover, (+)-trans-decursidinol exhibited competitive-type, and Pd-C-I and Pd-C-II mixed-type, while Pd-C-III showed non-competitive type inhibition of α-glucosidase. Docking simulations of these coumarins showed negative binding energies and a similar proximity to residues in the PTP1B and α-glucosidase binding pocket, which means they are closely connected and strongly binding with the active enzyme site. In addition, dihydroxanthyletin-type coumarins are up to 40 µM non-toxic in HepG2 cells and have substantially increased glucose uptake and decreased expression of PTP1B in insulin-resistant HepG2 cells. Further, coumarins inhibited ONOO−-mediated albumin nitration and scavenged peroxynitrite (ONOO−), and reactive oxygen species (ROS). Our overall findings showed that dihydroxanthyletin-type coumarins derived from A. decursiva is used as a dual inhibitor for enzymes, such as PTP1B and α-glucosidase, as well as for insulin susceptibility.
“…This weak binding (compared to covalent binding) between enzymes and carrier made it inevitable for enzymes dropping off. However, the reusability results were relatively higher than the reported data (Table 3), [29,[36][37][38][39][40][41] which was possibly attributed that there were some exposed oxygen active sites on MHNiO to strengthen the binding between enzyme and carrier through hydrogen binding.…”
Section: Reusability Of Enzymatic Reactorsmentioning
MOF‐derived porous NiO with hierarchical structure (MHNiO) was prepared based on thermolysis of Ni metal organic framework (Ni‐MOF), which was used as carrier for the immobilization of horseradish peroxidase (HRP) and cytochrome C (Cyt c). The pore size of MHNiO was tuned as 11.8 nm to match the size of free enzyme so as to depress the aggregation of the enzymes in the pore. Meanwhile, the hierarchical structure allowed the substrates concentrated in the vicinity of the enzymes. The obtained enzymatic reactors exhibited better thermal stability, storage stability and reusability. For example, over 83 % of its original activity after 1 h incubation at 70 °C could be remained compared to 18.1 % or 38.4 % remained activity of free HRP and Cyt c, respectively; After 12 cycles of use, over 53 % of original catalytic activity of both the enzymatic reactor could be maintain. The enzymatic kinetic data (Km, Vmax, kcat) and thermodynamic data (Ka, ΔH, ΔS and ΔG) indicated that the improved catalytic performance was attributed to the affinity, selectivity and binding of enzyme to substrate. The two enzymatic reactors could be applied in the fast degradation of 2,4‐dichlorophenol and rifaximin in artificial wastewater, a complete degradation of 2 mg ⋅ mL−1 of 2,4‐dichlorophenol or 20 μg ⋅ mL−1 of rifaximin was achieved in only 20 min.
“…Kong et al proposed an SPR-based biosensor consisting of a multi-enzyme nanoreactor with a hierarchical structure using α-Glucosidase (GAA) and Glucose Oxidase (GOx) for anti-diabetic drug screening of NPs. The generated glucose by GAA is oxidized by GOx and the byproduct of hydrogen peroxide changes the shape of silver nanoprism to nanodiscs which can be detected by SPR [ 62 ]. Fig.…”
Natural products (NPs) are a valuable source in the food, pharmaceutical, agricultural, environmental, and many other industrial sectors. Their beneficial properties along with their potential toxicities make the detection, determination or quantification of NPs essential for their application. The advanced instrumental methods require time-consuming sample preparation and analysis. In contrast, biosensors allow rapid detection of NPs, especially in complex media, and are the preferred choice of detection when speed and high throughput are intended. Here, we review diverse biosensors reported for the detection of NPs. The emerging approaches for improving the efficiency of biosensors, such as microfluidics, nanotechnology, and magnetic beads, are also discussed. The simultaneous use of two detection techniques is suggested as a robust strategy for precise detection of a specific NP with structural complexity in complicated matrices. The parallel detection of a variety of NPs structures or biological activities in a mixture of extract in a single detection phase is among the anticipated future advancements in this field which can be achieved using multisystem biosensors applying multiple flow cells, sensing elements, and detection mechanisms on miniaturized folded chips.
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