Characterization of Crocetin-Monoglucuronide as a Neuron-Protective Metabolite of Crocin-1.

Abstract

Crocins are important apocarotenoids in the extract of saffron (Crocus sativus L.) and fruits of gardenia (Gardenia jasminoides E.). Crocins have shown versatile biological activities and thus they have been considered to be promising therapeutics for neurodegenerative and heart diseases. Metabolism studies report that crocetin-monoglucuronide (CM) is produced and detected in rat blood plasma after oral administration of crocins. However, due to the lack of standard compound of CM, its unambiguous identification, quantification, and bioactivity studies have been hindered. CM is synthetized and its existence in blood plasma in Sprague-Dawley (SD) rats is quantified. The pharmacokinetic studies show that CM is produced in blood and brain after oral administration of crocin-1. It is then discovered that CM possesses neuroprotective activity against beta-amyloid (Aβ) toxicity in PC-12 cells and drosophila models. The enzymatic assay shows that CM can effectively inhibit AChE and docking studies indicate that CM may bind in the gorge channel of AChE. The work discovered that CM is a neuron-protective metabolite of the orally administrated crocin-1. It is demonstrated that AChE can be one of the targets of CM in its neuron-protective activity.