Neohesperidin dihydrochalcone: Presentation of a small molecule activator of mammalian alpha‐amylase as an allosteric effector

Abstract

Flavonoids and their precursor trans-chalcone have been reported as inhibitors of mammalian alpha-amylase. With regard to this background, neohesperidin dihydrochalcone (NHDC) effect was investigated toward porcine pancreatic alpha-amylase (PPA), and found to be an activator of the enzyme. The maximal activation (up to threefold) was found to occur at 4.8mM of NHDC, which could be considered to have a high activation profile, with regard to the alpha and beta parameters (alpha<1<beta). NHDC is a non-essential activator of the enzyme and based on the results obtained from modeling tools, it is suggested to interact with PPA at a hydrophilic site located at the N-terminal, far from the active site of the enzyme.

Effect of neohesperidin dihydrochalcone on the activity and stability of alpha‐amylase: a comparative study on bacterial, fungal, and mammalian enzymes

“…BAA activity of 422 IU l −1 in the presence of 2.25 g dl −1 starch and AOA activity of 490 IU l −1 obtained by 0.5 g dl −1 starch were chosen for further experimentations. In order to enable better comparison of this study results with our previous work on PPA (used at 560 IU l −1 ) (Kashani‐Amin et al ., 2013), adjustment of the activities of the three enzymes was done as much as possible in order to use close values. The final activities used for BAA and AOA that are not exactly the same as PPA are due to the limitations of experimental conditions (e.g., need to use high concentrations of starch for BAA).…”

“…Different concentrations of NHDC were incubated with the enzyme at 25 °C and then stirred gently for 10 min prior to activity assay as it was performed for PPA (Kashani‐Amin et al ., 2013). Data were obtained by a Shimadzu UV‐1800 (Shimadzu Corp., Kyoto, Japan) spectrophotometer, and activities were calculated by the UV‐Probe software.…”

“…Xanthine derivatives, including caffeine, are also activators of PPA, but again in a non dose‐dependent manner (Kashani‐Amin et al .). In a recent study, we introduced neohesperidin dihydrochalcone (NHDC) (Scheme ), a synthetic glycoside chalcone, as a dose‐dependent, allosteric activator of PPA (Kashani‐Amin et al ., 2013).…”

In SilicoMolecular Docking andIn VitroAntidiabetic Studies of Dihydropyrimido[4,5-a]acridin-2-amines

“…Two interacting binding sites were identified [37], one near the entrance of the central beta-barrel of the enzyme and the other near the N-terminal of the protein [39]. The docked structures showed binding energy in the range of −4.2 to −4.8 Kcal/mol.…”

Application of a liquid chromatography–tandem mass spectrometry method to the pharmacokinetics, bioavailability and tissue distribution of neohesperidin dihydrochalcone in rats

“…Its characteristics include: sweetness, refreshing taste, aftertaste durable and an excellent effect in shielding against bitterness (Marti et al, 2008;Yeomans et al, 2007). NHDC is also reported to have antioxidation activity (Choi et al, 2007) and inhibiting mammalian alpha-amylase (Kashani-Amin et al, 2013). However, it is reported to have embryotoxicity, teratogenicity and other toxic effects related to high dosage in rats or humans (Lina et al, 1990;Waalkens-Berendsen et al, 2004) and it has become an emerging pollutant in the environment (Gan et al, 2013;Kashani-Amin et al, 2013;Scheurer et al, 2009).…”