Mechanistic Insights into the Biological Effects of Aronia melanocarpa Through In vitro Assays, Molecular Docking and Bioinformatic Analysis

Abstract Aronia melanocarpa is recognized to be a polyphenol-rich fruit with promising bioactivities; however, there are limited multidisciplinary analyses of it using both experimental and computational analyses. The current study critically investigated aqueous (AWE) and ethanolic (AEE) extracts of A. melanocarpa grown in Turkey that defined their phytochemical composition and biological relevance via in vitro , in silico , and bioinformatics studies. LCMS/MS quantitatively determined quinic acid, cyanidin-3-O-glucoside and chlorogenic acid as the most prevalent phenolic compounds in both extracts. The two extracts showed strong antioxidant activity in a range of methods (DPPH, ABTS, FRAP, CUPRAC, and metal-reducing) with AEE always showing better performance and coming close to the established standard antioxidants. The extracts had strong inhibition of therapeutic enzymes including acetylcholinesterase, alpha-glucosidase, and human carbonic anhydrase I-II which was better than the inhibitors. Antimicrobial testing showed a broad-spectrum antibacterial activity, which was indicated by low minimal inhibitory concentration, especially of the ethanolic extract. Cytotoxicity profiling also revealed that AEE had a selective antiproliferative effect on A549 lung cancer cells and a limited response in MCF-7 breast cancer cells. Cyanidin-3 -O -glucoside was identified as the leading contributor to the enzyme inhibition activity by induced -fit molecular docking studies. Furthermore, bioinformatic enrichment studies linked molecular targets that were predicted with pathways related to the oxidative stress, metabolic regulation, inflammation, and cell survival. These findings demonstrate that A. melanocarpa exerts its biological effects through multi-target and network-level mechanisms, supporting its potential as a functional food.