Cyclodextrin-Based Supramolecular Complex Modulates the Bioaccessibility and Vascular Activity of Plinia peruviana...

Cardiovascular diseases remain a major global health challenge, driving the search for plant-derived bioactive systems with improved pharmaceutical performance. Plinia peruviana, a Brazilian native species, is a rich source of phenolic compounds with well-documented biological activities. However, limitations related to physicochemical instability and low oral bioavailability hinder its practical application. Herein, a supramolecular complex between the ethanolic extract of P. peruviana branches and β-cyclodextrin was developed to improve the biopharmaceutical properties of the extract. Total phenolic content was determined by visible spectrophotometry, while inclusion complex formation was confirmed by nuclear magnetic resonance and Raman spectroscopy. Vasodilatory activity was evaluated through ex vivo vascular reactivity assays using isolated mesenteric arterial beds, and oral safety was assessed in acute and subchronic exposure models following internationally accepted guidelines. In addition, simulated gastrointestinal digestion was employed to investigate phenolic stability and bioaccessibility. The supramolecular complex exhibited biologically relevant vasodilatory activity, showed low oral toxicity, and significantly enhanced the intestinal bioaccessibility of phenolic compounds. Overall, these findings demonstrate that cyclodextrin-based supramolecular systems represent a promising pharmaceutical delivery strategy for improving the biopharmaceutical performance of phenolic-rich plant extracts through enhanced intestinal bioaccessibility and a favorable oral safety profile. These characteristics support their further investigation as plant-based delivery systems for future phytopharmaceutical development for cardiovascular applications.