Cocrystal of Apigenin with Higher Solubility, Enhanced Oral Bioavailability, and Anti-inflammatory Effect

Apigenin (4',5,7-trihydroxyflavone, APG) is a bioflavonoid found in some herbs, vegetables, and fruits. APG can reduce inflammation, which is associated with many chronic aging diseases. However, the solubility and bioavailability of APG is quite low; thus, its utility in the body is questionable. Herein, a new cocrystal (APG-BPY) assembled by APG and BPY (4,4'-bipyridine) has been successfully prepared. A single-crystal structure of this cocrystal was illustrated, and comprehensive characterizations were performed in detail. In aqueous buffer, experiments with the dissolution profile of APG-BPY showed that the maximum concentration of APG is approximately similar to 40 times higher than that of APG raw material. This result yielded an optimized pharmacokinetics performance, as demonstrated by the improved relative bioavailability of F-rel = 3.9. Furthermore, the anti-inflammatory response in vivo was evaluated by pharmacodynamic experiments; the percentage inhibition of inflammation was 56% for APG-BPY, in comparison with 26% of pure APG. The enhanced efficacy and low toxicity results indicate the development of a pharmaceutically acceptable form of APG that may be potentially clinically available.