A streamlined one-pot process for the continuous extraction, biotransformation, and cyclodextrin encapsulation of bioavailable baicalein from Scutellaria baicalensis.

BACKGROUND: In plants, flavonoids predominantly exist as glycosides, which exhibit high polarity and low lipid solubility, thereby limiting their absorption across the intestinal mucosa. Baicalin (Bi), a glycoside, and its aglycone baicalein (Ba), derived from Scutellaria baicalensis, serve as representative examples of this bioavailability challenge. PURPOSE: The aim of this study was to develop a green, one-pot strategy integrating ultra-high pressure (UHP)-assisted hydroxypropyl-β-cyclodextrin (HP-β-CD) extraction with endogenous enzyme-mediated in situ biotransformation and HP-β-CD inclusion. This approach was designed to simultaneously extract baicalin (Bi) and convert it into baicalein (Ba), thereby enhancing its water solubility and oral bioavailability. STUDY DESIGN: In this integrated system, UHP first disrupts plant cell walls and membranes, increasing tissue permeability and allowing water and HP-β-CD to penetrate cells for efficient extraction of both compounds. HP-β-CD plays multiple roles: it acts as an inclusion carrier, improves extraction efficiency, drives the enzymatic conversion equilibrium toward Ba formation via in situ product sequestration, and finally forms a stable Ba-HP-β-CD complex. This design significantly enhances the water solubility of Ba and bypasses the conventional gastrointestinal absorption bottleneck which typically requires sequential hydrolysis and reconjugation. METHODS: The entire procedure uses water as the sole solvent, avoiding organic solvents and high temperatures. This one-pot process combines UHP treatment, endogenous enzyme-mediated biotransformation, and HP-β-CD inclusion in a single step, with low energy consumption. RESULTS: Compared with MAE-70E (microwave-assisted extraction with 70% ethanol), MAE-W (microwave-assisted extraction with water), HRE-70E (heat reflux extraction with 70% ethanol), and HRE-W (heat reflux extraction with water), the UHP-HP-β-CD extract exhibited superior in vitro antibacterial and anti-inflammatory activities. Furthermore, the oral bioavailability of Bi achieved by this strategy was 2.72-, 3.19-, 2.99-, and 3.40-fold higher than that of the four control methods, respectively. CONCLUSION: This integrated green strategy successfully combines efficient extraction, in situ biotransformation, and enhanced bioavailability in a single, environmentally friendly process. It offers a novel and promising approach for the high-value utilization of natural products.