The effects of β boswellic acid and different levels of glucose on tau aggregation: an in vitro study

Abstract

Introduction: Today, Alzheimer's disease is one of the most common diseases whose prevalence is increasing. In order to deal with this disease, one of the adopted strategies is the use of natural compounds, such as frankincense extract (β boswellic acid). The aim of this study was to investigate the interaction of β bosowellic acid (as the most important compound in frankincense plant) with Tau protein (as one of the proteins involved in Alzheimer's disease) along with the effect of β boswellic acid on Tau protein aggregation. Due to the close relationship between Alzheimer's disease and diabetes, the Tau-Boswellic acid interaction in the presence of different concentrations of glucose will also be studied. Methods: Tau protein was stabilized on the chip and its interaction with β boswellic acid at physiological pH and different temperatures in the presence and absence of glucose was investigated using surface plasmon resonance and molecular modeling methods. Also, the effect of β boswellic acid on the accumulation of Tau protein in vitro was studied by the thioflavin T assay. The intracellular aggregation was studied by flowcytometry. Results and discussion: Based on the results, at 298 K, a stable complex (KD=8.45×10-7 M) was formed between Tau protein and β boswelic acid, which increased with temperature enhancement. Also, the values related to the thermodynamic parameters of enthalpy, entropy and Gibbs free energy were equal to 4.86×104(Kcal/M), 2.79×102(Kcal/KM) and -3.46×104 (Kcal/M) 2 respectively, which indicates that the connection is thermodynamically favorable and the hydrophobic bond involved in the interaction. Molecular modeling studies showed that there is a hydrophobic bond between β boswellic acid and Tau protein, which confirms the thermodynamic results. The amount of KD increased in the presence of enhanced glucose concentrations (0-20 mM), indicating a decrease in the binding affinity between Tau protein and β boswellic acid in the presence of glucose. On the other hand, β boswelic acid had no effect on the accumulation of Tau protein, either in vitro or intracellularly. Conclusion: β boswellic acid possesses a relatively good tendency to bind to the Tau protein through hydrophobic bonds, which are affected by different concentrations of glucose. While this natural compound had no effect on Tau protein aggregation.