A comparative analysis of bioactive phytochemicals in Cynanchum viminale (L.) L. and Pergularia daemia (Forssk.) Chiov. from Saudi Arabian folk medicine

Abstract

The dual global health crises of antimicrobial resistance and cancer demand the urgent discovery of novel therapeutic leads. The medicinal plants Cynanchum viminale and Pergularia daemia (Apocynaceae) represent a rich reservoir of bioactive compounds used in traditional medicine, yet a comprehensive comparative analysis of their bioactivities and molecular mechanisms has remained elusive. This study provides an integrated in vitro and in silico analysis of the methanolic extracts of C. viminale and P. daemia. Phytochemical profiles were delineated by HPLC. Bioactivities were systematically evaluated via a battery of five antioxidant assays (DPPH, ABTS, FRAP, H₂O₂, NO), broad-spectrum antimicrobial screening against six pathogens, and cytotoxicity assays against a panel of six human cancer cell lines (HepG-2, MCF-7, HCT-116, A-549, PC-3, A-431). To deconstruct the molecular basis of these activities, in silico molecular docking was performed against two pivotal therapeutic targets: Epidermal Growth Factor Receptor (EGFR) and Dihydrofolate Reductase (DHFR). A striking functional divergence between the two plants was discovered. P. daemia exhibited superior antioxidant and broader-spectrum antibacterial activity, a finding strongly correlated with its unique phenolic profile, particularly the potent DHFR-binding Chlorogenic acid and the bioenhancing alkaloid Piperine. In stark contrast, C. viminale demonstrated dramatically superior cytotoxic potency across all tested cancer cell lines, with IC₅₀ values as low as 24.37 µg/mL against HepG-2 liver cancer. Molecular docking brilliantly illuminated the mechanism behind this divergence: the potent cytotoxicity of C. viminale is driven by its principal alkaloids, Protopine and Berberine, which showed high-affinity binding to the ATP-binding site of EGFR, a key driver of cancer proliferation. DHFR, conversely, was identified as a common molecular target for potent binders from both plants (Evodiamine, Piperine, Chlorogenic acid), providing a unifying mechanism for their shared antimicrobial properties.

Keywords: C. viminale; P. daemia; Bioactivity; Medicinal plants; Phytoconstituents.