Effect of Drying Methods on Bioactivity of Pyrostegia venusta Extracts: Antioxidant Assays, Cytotoxicity, and Computational Approaches

<b>Background/Objectives:</b> <i>Pyrostegia venusta</i> (Cipó-de-São-João), a native Brazilian Cerrado plant, is rich antioxidant phytochemicals. The efficacy of herbal extracts, particularly their phenolic content and antioxidant potential, is influenced by the extraction method used. This study investigated the effects of two drying methods, hot-air oven drying and freeze-drying, on the antioxidant activity, cytotoxicity, and molecular interactions of aqueous extracts from the flowers and leaves of <i>P. venusta</i>. <b>Methods:</b> antioxidant capacity was assessed using DPPH, FRAP, and Folin-Ciocalteu assays; phenolic profiles were characterized by UHPLC; and cytotoxicity was evaluated via the MTT assay in HaCaT human keratinocyte cells. Additionally, in silico ADMET predictions were conducted to assess pharmacokinetics and potential toxicity, followed by molecular docking to evaluate interactions with the proliferation markers Ki-67 and PCNA. <b>Results:</b> freeze-dried extracts, particularly from the flowers, contained higher concentrations of phenolic compounds and exhibited superior antioxidant activity compared to hot-air oven-dried extracts. UHPLC analysis identified a range of bioactive phenolics including caffeic, chlorogenic, gallic, ferulic, and p-coumaric acids, quercetin, and anthocyanidins such as pelargonidin-3-O-glucoside and peonidin-3-O-glucoside, with distinct compositional differences between leaves and flowers. ADMET analysis revealed generally favorable pharmacokinetic properties for most compounds. Docking simulations indicated that multiple phenolics showed synergistic interactions with Ki-67 and PCNA. <b>Conclusions:</b> our findings highlight freeze-drying as the optimal method for preserving bioactive compounds in <i>P. venusta</i> and support the therapeutic potential of its flower extracts. The evidence supports the notion that the biological effects of <i>P. venusta</i> are driven by synergism among multiple constituents rather than isolated compounds.