[ $\beta$ ]-Secretase (BACE1) Inhibitors from Pomegranate (Punica granatum) Husk

• Published in: Archives of pharmacal research Vol. 28; no. 12; pp. 1328 - 1332
• Main Authors: Kwak Hye-Min, Jeon So-Young, Sohng Bang-Ho, Kim Jong-Guk, Lee Jin-Man, Lee Kyung-Bok, Jeong Hyun­Hee, Hur Jong-Moon, Kang Young-Hwa, Song Kyung-Sik
• Format: Journal Article
• Language: Korean
• Published: 2005
• Subjects: Punicalagin; Ellagic acid; Pomegranate (Punica granatum); Alzheimer's disease
• ISSN: 0253-6269; 1976-3786

In the course of screening for anti-dementia agents from natural products, two $\beta$-secretase (BACE1) inhibitors were isolated from the husk of pomegranate (Punica granatum) by activity-guided purification. They were identified as ellagic acid and punicalagin with $IC_{50}$ values of 3.9 $\times$$10^{-6}$ and 4.1$\times$$10^{-7}$ M and Ki values of 2.4$\times$$10^{-5}$and 5.9$\times$$10^{-7}$ M, respectively. The compounds were non-competitive inhibitors with a substrate in the Dixon plot. Ellagic acid and punicalagin were less inhibitory to $\alpha$-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, thus indicating that they were relatively specific inhibitors of BACE1.