In SilicoInvestigation of Traditional Chinese Medicine Compounds to Inhibit Human Histone Deacetylase 2 for Patients with Alzheimer’s Disease

Abstract

Human histone deacetylase 2 (HDAC2) has been identified as being associated with Alzheimer's disease (AD), a neuropathic degenerative disease. In this study, we screen the world's largest Traditional Chinese Medicine (TCM) database for natural compounds that may be useful as lead compounds in the search for inhibitors of HDAC2 function. The technique of molecular docking was employed to select the ten top TCM candidates. We used three prediction models, multiple linear regression (MLR), support vector machine (SVM), and the Bayes network toolbox (BNT), to predict the bioactivity of the TCM candidates. Molecular dynamics simulation provides the protein-ligand interactions of compounds. The bioactivity predictions of pIC50 values suggest that the TCM candidatesm, (−)-Bontl ferulate, monomethylcurcumin, and ningposides C, have a greater effect on HDAC2 inhibition. The structure variation caused by the hydrogen bonds and hydrophobic interactions between protein-ligand interactions indicates that these compounds have an inhibitory effect on the protein.

Network Medicine for Alzheimer’s Disease and Traditional Chinese Medicine

“…In addition, combinations of the individual alkaloids berberine, coptisine, and palmatine cooperatively inhibited AChE [ 51 ]. Another enzyme associated with AD is human histone deacetylase 2 (HDAC2), and one study utilized the largest TCM database to investigate compounds that could inhibit HDAC2 [ 52 ]. Multiple linear regressions, support vector machines, and the Bayes network toolbox were used to predict how the most significant TCM compounds from the database would inhibit HDAC2.…”

“…Multiple linear regressions, support vector machines, and the Bayes network toolbox were used to predict how the most significant TCM compounds from the database would inhibit HDAC2. Based on results of these predictions, the compounds Bontl ferulate, monomethylcurcumin, and ningposides C inhibit HDAC2 most effectively [ 52 ]. These extracts and compounds should be investigated to see if they have other favorable effects on the AD network.…”

Epigenetic Mechanisms of Integrative Medicine

“…Of those, TCM compounds such as Ningposides C and Monomethylcurcumin act as HDAC2 inhibitors [36] and constitute examples of Type 1 direct pathway modulators (Figure 4). …”

Computational Investigation into the Interactions of Traditional Chinese Medicine Molecules of WenQingYin with GluR2

“…Traditional Chinese medicine (TCM) plays an important role in Asia, with an increasing number of TCMs being used to treat diseases, such as influenza [ 1 ], diabetes [ 2 , 3 ], cancer [ 4 , 5 , 6 , 7 ], and neurological disorders [ 8 , 9 ]. TCM has a broad range of applications because it encompasses a large number of compounds.…”

“…Kum et al used Jia Wei Liu Jun Zi Tang to treat Parkinson’s disease in clinical trials and improve patients’ communication abilities [ 8 ]. Hung et al investigated the inhibitory effect of a series of TCMs on human histone deacetylase 2, which is implicated in Alzheimer’s disease [ 9 ]. These studies show that TCM have beneficial effects in neurological disorders.…”