The Evaluation of Anticancer, Antioxidant, Antidiabetic and Anticholinergic Potentials of Endemic Rhabdosciadium microcalycinum Supported by Molecular Docking Study

Abstract

AbstractLung cancer is the most common cancer worldwide and the leading cause of cancer‐related death. Plant‐derived natural products and compounds are an inspiring source of chemotherapeutic agents. Alzheimer's disease (AD) is linked to the decline of acetylcholine (ACh) effects in the brain, so acetylcholinesterase (AChE) inhibitors are important in the treatment of AD. In this study, the chemical components and bioactivity of ethanolic extract of Rhabdosciadium microcalycinum (RM) was investigated by various methods. The lipophilic components of RM was determined by gas chromagraphy‐mass spectrometry (GC‐MS). Antioxidant activicty tests were evaluated with FCAP (Ferrous chelating antioxidant power assay), FRAP (Ferric reducing antioxidant power assay), ABTS (2,2′‐Azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt assay) and DPPH (2,2‐diphenyl‐1‐picrylhydrazyl assay). The anticancer effect of RM was evaluated by WST‐1 (4‐[3‐(4‐iodophenyl)‐2‐(4‐nitrophenyl)‐2H‐5‐tetrazolio]‐1,3‐benzene disulfonate), colony formation, wound healing and CDDE (cell death detection Elisa) analysis on A549 lung cancer cells. Enzyme inhibition effects of RM was determined against AChE and α‐glycosidase (AG) enzymes. According to the results of molecular docking found in the study; With a docking score of −4.56 for HP5 protein, −6.23 for BXO protein, −5.25 for AFI protein, −3.90 for gly protein and −7.74 for AChE protein, Telecinobufagin molecule was found to have higher activity than other molecules. After docking calculations, Absorption, Distribution, Metabolism, Excretion and Toxicity (ADME/T) analysis was performed to examine the effects and reactions of molecules on human metabolism. RM inhibited the viability of A549 cells dose‐dependent manner (IC50=117.15±8.58 μg/mL), and it was also observed that RM suppressed colony formation, prevented cell migration and directed the cells to apoptosis. RM has important lipophilic components, and significant antioxidant and enzyme inhibition potential. IC50 values of RM for AChE and AG enzymes were found as 35.86 mg/mL, and 10.14 mg/mL, respectively. In conclusion, the findings of this study reveal that ethanol extract from the aerial part of Rhabdosciadium microcalycinum may be a potential therapeutic agent for the treatment of human lung cancer and Alzheimer's disease, due to its phytochemical components.