In Silico Study of Centella asiatica Active Compound as BACE1 Inhibitor in Alzheimer’s Disease

Abstract

Alzheimer (AD) is a chronical neurodegenerative disease which is the 6 th leading cause of death worldwide. About 36 million cases in the world and may increase to 115 million in 2050. The pathological cause of AD is the presence of residual Aβ peptides. Aβ peptides is produced in the cleavage process of the amyloid precursor protein (APP) sequentially by Beta amyloid precursor protein cleavage enzyme 1 (BACE1) and γ-secretase. Flavonol, germacrene B, and sitosterol are compounds found in Centella asiatica which is has potential as BACE1 inhibitor. The aim of this study was to analyze the interaction between BACE1 with flavonol, germacrene B and sitosterol by molecular docking to predict the BACE1 inhibitor potent of those compound. We obtained BACE1 from RSCB database, flavonol, germacrene B and sitosterol from PubChem database. Molecular dockcing was done using Hex 8.0.0. The docking result were vizualized with Discovery Studio 3.5. Interaction of BACE1 resulted binding energy for sitosterol was -239.7 kcal/mol , flavonol was -188.1 kcal/mol, and germacrene B was -185.6 kcal/mol. Flavonol and sitosterol bound to the active site of BACE1 involving Thr232 and Ile110 on flavonol, while Tyr71 on sitosterol. All of the active compounds didn't have the interaction at S1' subsite, which is the center of BACE1 active site which has become the key of APP activation from BACE1. This study has shown that flavonol and sitosterol had potential to reduce BACE1 activity but not directly inhibit BACE1 activity.

Current Naturopathy to Combat Alzheimer’s Disease

“…The phenylpropanoid eugenol (also found in Clove ( Eugenia aromatica ), True Cinnamon ( Cinnamomum zeylanicum ) and Basil ( Ocimum basilicum ) and Clove Basil ( Ocimum gratissimum )) has a vast range of pharmaco-activity in context of neurodegeneration and AD, it potentiates the effect of Niacin (Nicotinic acid; Vitamin B3) in treating AD [ 242 , 243 ], reducing the chances of dementia and onset of AD on account of niacin deficiency [ 244 ], Eugenol increased acetylcholine level, decreased AChE activity (interacting with Tyr124 by hydrogen bond, Pi-Pi T-shaped interaction with Tyr337, pi-pi staked interaction with Ty341, and pi-alkyl interactions with His447, Trp286, Phe295 and Val294) [ 245 ], and increased the total muscarinic receptor in scopolamine-induced Charles-Foster albino rats [ 246 ], in another experiment on Wistar rats with aluminium-induced neurotoxicity followed by eugenol treatment, it resulted in a significant reduction NO and 8-OHdG levels, inhibition of caspase-3 activity, reduction of Bax protein levels and increase in levels of Bcl-2, SOD and GPx [ 247 ]. The volatile sesquiterpene compound germacrene (also found in hedgenettles ( Stachys inflata , Stachys lavandulaefolia, Stachys byzantina ), Indian pennywort ( Centella asiatica ), Palicourea tomentosa and Salvia syriaca ) [ 248 , 249 ] were found to inhibit BACE1, more specifically germacrene B interacts with Val93 residue of BACE1 as predicted by the in-silico study [ 250 ]. In contrast, germacrene D was found to have significant AChE inhibition activity [ 251 - 254 ].…”

In Silico Study of Entry Inhibitor from Moringa oleifera Bioactive Compounds against SARS-CoV-2 Infection

“…Sterilization of the target protein from water and contaminant ligands was carried out by Discovery Studio software to increase the optimization of binding energy. 20,24,25 Molecular docking and dynamic simulation…”

“…The bioactive compounds of M. oleifera were retrieved format from PubChem database (https://pubchem.ncbi.nlm.nih.gov/) in sdf format. 20…”