Isorhamnetin-3-rutinoside-7-rhamnoside the Antiradical and Antiacethylcholinesterase Flavonoid from the Hydro-ethanolic Extract of Costusspectabilis (Fenzl) K. Schum (Costaceae) and its Molecular Docking Study

Abstract

Introduction: Alzheimer’s disease is a neurodegenerative disease with no treatment. Costus spectabilis (Fenzl) K. Schum is a perennial rhizomatous herb traditionally used to treat several diseases. The aim of this study was to isolate antiradical and antiacetylcholinesterase compounds from Costus spectabilis (Costaceae), and to perform a molecular docking study of the active compound. Methods: Compounds were isolated using column chromatographic technics; structures of isolated compounds were determined using spectroscopic analysis and literature data. The antiradical scavenging potential was evaluated in vitro using DPPH as a free radical. The inhibition power of acetylcholinesterase was assessed in vitro using the Ellman reagent. Results: The phytochemical investigation of the studied extract led to four compounds : β- sitosterol (1), β-sitosterol-3-O-β-D-glucopyranoside (3), sucrose (2), and Isorhamnetin-3- rutinoside-7-rhamnoside (4). The extract showed a weak antiradical scavenging potential (IC50 : 0.2160 mg/mL). Among the tested compounds, compound 4 exhibited a very good antiradical scavenging activity (IC50 of 0.0012 mg/mL). Compound 4 also exhibited a good inhibition power of acetylcholinesterase with an inhibition percentage of 89% at 0.5mg/ml; this compound was followed by the hydro-ethanolic extract with an inhibition percentage of 87% at 2 mg/mL. Compound 4 exhibits high affinity for acetylcholinesterase and butyrylcholinesterase, key enzymes associated with Alzheimer’s disease, with binding energies of -9.8 kcal/mol and -10.8 kcal/mol, respectively. discussion: the antiradical evaluation of extract and compounds was performed. Among all the tested samples, compound 4 demostrated a very good antiradical potential with an IC50 of 0.0012 mg/ml very near of the IC50 of the ascorbic acid used as reference. This compound in terms of activity is followed by compound 2 and the crude extract with IC50 of 0.1240 mg/ml and 0.2160 mg/ml respectively. This result indicates that compounds in the extract act asynergistically. Compound 4 demostrated strong AChE inhibitory activity with inhibition percentages of 89% and 87% at 0.5mg/ml and 0.01 mg/mL respectively, with a very weak (4.12 and 4.88) activity of AChE. In term of activity, this compound was followed by the hydro-ethanolic extract which also demostrated strong inhibitory activity with an inhibiton percentage of 87% at 2 mg/mL. Compound 2 was the less active sample. These experimental results align well with molecular docking studies, which indicate that compound 4 exhibits high affinity for acetylcholinesterase and butyrylcholinesterase key enzymes associated with Alzheimer’s disease with binding energies of -9.8 kcal/mol and -10.8 kcal/mol respectively. Discussion: Results obtained for the two biological activities performed showed that in the extract studied, compounds react in the asynergically maner. Conclusion: The hydro-ethanolic extract studied can be considered a good inhibitor of AChE.