β-Secretase(BACE1) inhibitors from pomegranate (Punica granatum) husk

Abstract

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 IC50 values of 3.9 x10(-6) and 4.1x10(-7) M and Ki values of 2.4x10(-5) and 5.9x10(-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.

Neuroprotective Effects of Pomegranate Peel Extract after Chronic Infusion with Amyloid-β Peptide in Mice

“…Mice infused with Aβ and treated with PPE showed a significant reduction (11.2%) in the number of plaques (24.66 ± 0.52 plaques/sections, P < 0.01), when compared to Aβ infused animals (Fig 3). The reduction of plaque density can be linked to two specific inhibitors of β-secretase (BACE-1) present in the pomegranate peel, elagic acid (IC50 = 3.9 x 10–6 M) and punicalagin (IC50 = 4.1 x 10–7 M), or to the inhibition of y-secretase activity [30,31]. …”

Natural products as a source of Alzheimer's drug leads

“…An investigation of pomegranate husk Punica granatum L. (Lythraceae) identified the complex phenolic ellagic acid and punicalagin as weak inhibitors of BACE1, 187 while more potent glucopyranoside galloyl derivatives were isolated from Sanguisorba officinalis L. var. officinalis or var.…”

The Power of the Pomegranate: Biblical Fruit with Medicinal Properties

“…31 Neonatal brain injury from reduced oxygen and blood flow remains a significant cause of mortality and morbidity in infants, and lacks effective therapies for prevention and treatment. Dietary supplementation with foods rich in polyphenol compounds has been discovered recently to offer neuroprotection in adult animal models of ischemia and Alzheimer's disease.…”