jf8b01187_si_001.pdf (1.59 MB)
Traversal of the Blood–Brain Barrier by Cleavable l‑Lysine Conjugates of Apigenin
journal contribution
posted on 2018-06-20, 00:00 authored by Tsung-Yun Wong, Ming-Shian Tsai, Lih-Ching Hsu, Shu-Wha Lin, Pi-Hui LiangApigenin,
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 its absorption in vivo and prevents clinical use. Herein,
apigenin was directly conjugated with glycine, l-phenylalanine,
and l-lysine to give the corresponding carbamate derivatives,
all of which were much more soluble than apigenin itself (0.017, 0.018,
and 0.13 mg/mL, respectively). The Lys-apigenin carbamate 10 had a temporary sedative effect on the mice within 5 min of intraperitoneal
administration (single dose of 0.4 mg/g) and could be detected in
the mice brain tissues at a concentration of 0.82 μg/g of intact
Lys-apigenin carbamate 10 and 0.42 ug/g of apigenin at
1.5 h. This study accomplished the delivery of apigenin across the
BBB in a manner that might be applicable to other congeners, which
should inform the future development of BBB-crossing flavonoids.