Bioinformatic and experimental approaches to uncover the bio-potential of Mercurialis annua extracts based on chemical constituents

Mercurialis annua (M. annua) is a plant used traditionally in many parts of the world including Spain and Turkey. The present study was designed to investigate the biochemical composition and bioactive properties of M. annua extracts. Antioxidant capacity was determined by DPPH, ABTS, CUPRAC, FRAP, PBD, and MCA assays, as well as the quantification of total phenolic content (TPC) and total flavonoid content (TFC). Neuroprotective enzymes inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and antidiabetic potential against tyrosinase, α-amylase and α-glucosidase were also evaluated. The LC-MS-Q-TOF metabolomic analysis of different extracts of M. annua revealed the presence of several important compounds such as quercetin, rutin, kaempferol derivatives, caffeic acid, chlorogenic acid, and ferulic acid. Ethanol extract showed the highest TPC (31.03 ± 1.67 mg GAE/g). The 70 % ethanol/water extract showed excellent antioxidant activity in all assays. Ethanol extract exhibited the highest inhibition against AChE (2.31 ± 0.04 mg GALAE/g) and similar activity against BChE. Ethanol extract demonstrated considerable cytotoxicity in cytotoxicity assays against various cancer cell lines with the lowest IC50 values for breast (MDA-MB-231) and gastric cancer cells (HGC-27). Network pharmacology analysis was performed to identify biological pathways that could be modulated by these bioactive compounds. Computational analyses revealed strong binding affinities of M. annua compounds with proteins such as CDK4 and CDK2. These results support the use of these extracts in the development of therapeutic agents for neuroprotection, diabetic management, and cancer treatment.