In-vitro Neuro-2a cytotoxicity analysis and molecular docking investigation on potential anti-amyloid agents from Adiantum lunulatum

In neurodegenerative diseases, amyloid formation by some proteins cause neuronal damage and loss. To prevent this neuronal damage and loss certain pharmaceuticals are available. Many of these pharmaceuticals act on the neurodegenerative disease symptoms but not on the root cause. This study helps to detect more effective agents which directly act on the root cause and reduce the risk of neurodegenerative diseases. To identify new anti-amyloid agents, the folk medicinally important plant <i>Adiantum lunulatum</i> was collected, authenticated, dried, extracted with ethanol and analyzed by GC-MS method. The screening of the identified phytochemicals was done using the webservers swissADME and ProTox-II. <i>In-vitro</i> MTT assay using Neuro-2a cell lines was carried out to determine the cytotoxicity of the extract. The interactions of these phytochemicals with the amyloid forming peptides and proteins were predicted using the molecular docking tools such as AutoDock Vina and BIOVIA discovery studio visualizer 2020. Through GC-MS analysis, 18 different volatile phytochemicals were identified from the ethanol extract. From this, 7 phytochemicals were selected based on the computational non-toxicity prediction. <i>In-vitro</i> cytotoxicity analysis of the ethanol extract using Neuro-2a cell lines detected the IC₅₀ value of 0.09 mg/ml. Of these, the phytochemical <b>P1</b> (trans, trans-9, 12-Octadecadienoic acid, propyl ester) interacts with tau, and huntingtin proteins, <b>P2</b> (2-Pentadecanone, 6, 10, 14-trimethyl-) interacts with prion protein. The phytochemicals <b>P1</b>, <b>P3</b> (Ethyl oleate), <b>P4</b> (Octadecanoic acid, ethyl ester), and <b>P5 (</b>Phytol) interact with acetylcholinesterase. <b>P2</b>, <b>P4</b>, <b>P5</b> and <b>P6</b> (Henicosanal), interact with BACE-1. The phytochemical <b>P3</b> interacts with γ- Secretase. The interaction of P2 and P5 with BACE-1 and P3 with γ- Secretase show better inhibition in inhibitory constant (<i>K</i> _<i>i</i> ) analysis. These phytochemicals have been predicted to show significant potential against the formation or breakdown of peptide/protein amyloids, and further <i>in-vitro</i> studies are necessary to develop them into anti-amyloid agents.