Abstract
Despite their broad pharmacological potential, the clinical application of stilbenes derived from Cajanus cajan (L.) Millsp. leaves (CCMLs) is limited by their poor aqueous solubility, resulting in low oral bioavailability. In this study, an inclusion complex of stilbenes extracted from CCMLs and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was successfully developed to improve their solubility and oral bioavailability. The preparation conditions were optimized using the response surface methodology, with an optimum mass ratio of CCML extract (CCMLE) to HP-β-CD of 1.0:8.2 (g/g) and an optimal temperature of 33 °C for 2 h. The maximum inclusion efficiency of stilbenes was 82%, and the physicochemical properties of the inclusion complex were characterized. Both in vitro dissolution studies and in vivo pharmacokinetic evaluation demonstrated that HP-β-CD encapsulation significantly improved the solubility and dissolution rate of stilbenes compared to those of unformulated CCMLE. Notably, the relative bioavailability of cajaninstilbene acid (CSA), longistyle C (LLC) and 4-O-methylpinosylvic acid (MPA) increased to 198%, 177% and 131%, respectively. This work provides a simple and effective strategy to enhance the solubility and bioavailability of naturally derived stilbenes, offering promising potential for the development of other insoluble natural components for both functional food and pharmaceuticals.