Unleashing the biological power and chemical profile of Paracaryum hedgei extracts based on chromatographic, in vitro, and bioinformatic tools

Studies evaluating the chemical constituents and pharmacological potential of Paracaryum species (family Boraginaceae) were limited. The current study was designed to investigate, for the first time, the chemical profile, antioxidant, enzyme-inhibitory, and cytotoxic properties of P. hedgei Aytaç & R.R. Mill. Roots extracts recorded the highest total phenolic content (24.72–91.16 mg GAE/g). About 33 compounds were identified, and the aerial parts extracts were dominated by rosmarinic acid, rutin, and sagerinic acid. In general, the root extracts exhibited greater antioxidant activity than the extracts from the aerial parts. Among the solvents, The 70 % EtOH extract of roots showed the highest antiradical (DPPH: 207.90 mg TE/g; ABTS: 238.08 mg TE/g), ion-reducing (FRAP: 384.99 mg TE/g; CUPRAC: 615.27 mg TE/g), and total antioxidant activities (3.21 mmol TE/g), whereas the EtOAc and aqueous extracts from the aerial parts demonstrated the best chelating capacity. The enzyme inhibition varied according to the plant parts examined and the solvents employed for extraction. The EtOAc extract of the roots exerted the highest inhibitory effect towards the human carbonic anhydrase II (IC50: 2.32 μg/ml). The cytotoxicity of the extracts was tested against three cancer cell lines (HELA, A549, and HCT-116) and one healthy cell line (HEK-293). Specifically, the EtOAC extracts showed cytotoxic effects on HELA cells sourced from aerial parts (IC50: 106.30 μg/ml) and on HCT-116 cells sourced from roots (IC50: 96.82 μg/ml). Molecular docking results provided additional support for the enzyme inhibition capabilities of the extracts. Combined network pharmacology and molecular docking analyses revealed that phenolic acids from P. hedgei exert anti-cancer effects on cervical and colorectal adenocarcinoma by modulating key pathways, including retinoic acid metabolism, steroid biosynthesis, and inflammatory responses. These findings can provide a scientific starting point for the pharmaceutical potential of P. hedgei , and it can be considered a valuable source of natural bioactive compounds for functional nutraceutical and pharmaceutical applications.