Traversal of the Blood–Brain Barrier by Cleavable l-Lysine Conjugates of Apigenin

• DOI: 10.1021/acs.jafc.8b01187
• Publication Date: 2018-06-20T09:19:09Z
• Authors: Tsung-Yun Wong; Ming-Shian Tsai; Lih-Ching Hsu; Shu-Wha Lin; Pi-Hui Liang
• Keywords: Carbamate

Apigenin, a flavone abundant in parsley and celery, is known to act on several CNS receptors, but its very poor water solubility (<0.001 mg/mL) impedes absorption vivo prevents clinical use. Herein, apigenin was directly conjugated with glycine, l-phenylalanine, l-lysine give the corresponding carbamate derivatives, all of which were much more soluble than itself (0.017, 0.018, 0.13 mg/mL, respectively). The Lys-apigenin 10 had temporary sedative effect mice within 5 min intraperitoneal administration (single dose 0.4 mg/g) could be detected brain tissues at concentration 0.82 μg/g intact 0.42 ug/g 1.5 h. This study accomplished delivery across BBB manner that might applicable other congeners, should inform future development BBB-crossing flavonoids.