In silico analysis of bioactive compounds from ethanolic amber extract targeting BACE1: Potential implications for glucose metabolism

Ethanolic amber extract contains a mixture of terpenoids and other compounds with potential biological properties. This study aimed to explore in silico the interaction of selected constituents of amber extract on β-site amyloid precursor protein cleaving enzyme 1 (BACE1) since BACE1 inhibition, in addition to its influence on neurodegeneration, may affect insulin receptor levels in the liver, thereby contributing to the control of glucose homeostasis. By using the CB-Dock2 web-based software for protein-ligand interactions, auto blind docking on BACE1 was performed with compounds present in the amber extract, particularly terpenes (isopimaric acid methyl ester, borneol, camphor, 2-fenchanol, m-cymene and communic acid) and succinic acid derivatives. All six terpenes, as well as succinic acid and its ester, displayed an appreciable binding affinity, as documented by the respective Vina scores. In particular, isopimaric acid methyl ester and communic acid showed the strongest interactions. Computational ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) prediction allowed to evaluate the provisional properties of the compounds. The results obtained and presented here suggest that an interaction of terpenes and succinates, present in the ethanolic amber extract, with BACE1 protein is possible, potentially counteracting the loss of insulin receptor. Therefore, this finding may suggest a new approach to glycemic control.