Intestinal absorption and neuroprotective effects of kaempferol-3-O-rutinoside

Abstract

Kaempferol-3-O-rutinoside (K3R) has been proven to have biological activities for the prevention and treatment of central nervous system (CNS) diseases. However, the details of its absorption from the gastrointestinal tract and transport across the blood–brain barrier (BBB) are not clear. Therefore, to provide a basis for its efficacy, we explored its intestinal absorption with Caco-2 monolayer cells, rat orthotopic intestinal perfusion, its transport across a BBB model based on bEnd.3 monolayer cells and its pharmacological effects on PC12 cells in terms of neuropathy. The results indicated that the transport of K3R is concentration dependent; moreover, the apparent permeability coefficient (P_app) of K3R lacked directionality, and the efflux rate after adding P-glycoprotein inhibitor did not show a significant change. K3R was found to be completely absorbed in the intestines of rats, and the absorption process follows the first-order kinetics. K3R can pass through the BBB with passive diffusion. The neuroprotective effects of K3R were related to stabilization of the mitochondrial membrane and a decrease in reactive oxygen species. These results demonstrated that K3R can be absorbed in a relatively moderate ratio in the gastrointestinal tract and transported to the brain. Thus, K3R may be a potent drug for the prevention and treatment of neurodegenerative diseases such as Parkinson's disease.