Solubility and bioavailability enhancement of baicalin by modified citrus pectin: preparation, in silico, in vitro and in vivo evaluation

Baicalin, a flavonoid compound with various health benefits, faces significant limitations in its application due to poor solubility. Identifying a nontoxic, biodegradable, and readily available solubilizer is therefore critical for improving the solubility of baicalin and related analogues. This study aimed to evaluate the potential of citrus pectin and its acid-hydrolyzed derivatives to improve baicalin solubility, elucidating the underlying mechanisms of solubilization. Three fractions, MCP-1, MCP-2, and MCP-3, were obtained via partial acid hydrolysis followed by anion exchange chromatography. The results demonstrated that MCP-3, composed of 91.2 % galacturonic acid and 8.8 % rhamnose, exhibited the highest efficacy in enhancing baicalin solubility. Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermodynamic, molecular dynamics (MD) simulation confirmed that MCP-3 adopted a helical structure in solution, encapsulating baicalin within its helical cavity through hydrogen bonding between carboxyl and hydroxyl groups, as well as hydrophobic interactions and van der Waals forces. The MCP-3/baicalin complex exhibited good pH and temperature stability. Pharmacokinetic studies demonstrated that MCP-3 significantly enhanced the in vivo bioavailability of baicalin by 1.95-fold, and the complex exhibited low cytotoxicity. This study offers a promising strategy for the development of more effective flavonoid-based products.