Metabolomics and Anticancer Potential of the Aerial Parts of Dryopteris ramosa against Cancerous Cell Lines Assisted with Advanced Computational Approaches

Abstract

Introduction: Dryopteris ramosa is a high-altitude plant of moist and shady habitat. Its aerial parts are edible and orally administered as an antibiotic and effective aphrodisiac. They are also used as pesticides, astringents, and febrifuges.

Aim: The present study aimed to elucidate the plant's medicinal potential as an anticancer agent. Extracts of Dryopteris ramosa were examined for cytotoxic effects against AGS, A549, and HCT116 cell lines. The project also aimed to evaluate the phytochemical constitutents of the plant. For this purpose, GC-ToF-MS analysis was executed to identify the bioactive compounds in the aerial parts extract of Dryopteris ramosa. As a result, 93 different phytochemicals were identified from the spectral properties of GC-ToF-MS which contain 19 compounds of high peaks having reported anti-inflammatory, Anti-diabetic, Antibacterial, Analgesic, and antioxidant potential.

Methods: Three different cell lines have been treated against Ethanol, Methanol, Ethyl acetate, Water, Chloroform, Acetone, and n-hexane extracts from the aerial parts of Dryopteris ramosa. These cell lines were checked and were ranked in lethality based on IC⁵⁰ value. The extract samples were processed as serial dilution from high concentrations (500 ug/ml). All the three cell lines were treated for 48 hours.

Results: Extracts showed a significant effect in different cell lines (based on IC50 less than 200 ug/ml). Performing the in vitro anticancer activity against the three different cell lines in Ethyl Acetate, Methanol, n-hexane, Chloroform and Acetone extract of Dryopteris indicated that anticancer activity of the plant is high against AGS and A549 cell line while less prominent in HTC116 cell lines through MTT Assay. In silico drug-likeness and ADMET analysis were studied of the compounds, that exhibit considerable drug likenesses, phytochemical medicinal chemistry, and a promising ADMET score and no toxicity. The candidate compounds were chosen for further elucidation by Molecular Docking and dynamic simulations. Employing the molecular docking approach for virtual screening of the phytochemicals it was found that the compounds Germacrene showed remarkable results towards BCL2 with -7 Kcal/Mol and a-D-(+)-Xylopyranose showed significant docking results towards 5P21 with -7.1 Kcal/Mol.

Conclusion: For multi-scale frames structural aberrations and fluctuations identification of the docked complexes, a molecular dynamics analysis was performed for a 100 ps simulation run by accessing the online tool of MDweb simulations. These molecular docking and simulation analyses also revealed that both the phytochemicals have a stable interaction with the cancer-related proteins BCL2 and 5P21.

Keywords: Dryopteris ramosa; GC-ToF-MS analysis; anticancer potential; computational approaches; molecular docking and simulation; pesticides..