In Vitro Biological Activity Of Salvia Fruticosa Mill. Infusion Against Amyloid Beta-Peptide-Induced Toxicity And Inhibition Of Gsk-3 Beta, Ck-1 Delta, And Bace-1 Enzymes Relevant To Alzheimer'S Disease

Salvia species have been traditionally used to improve cognition and have been proved to be a potential natural treatment for Alzheimer's disease. Salvia fruticosa Mill. (Turkish sage or Greek sage) demonstrated to have anticholinergic effects in vitro.The aim of this study was to understand the mechanism underlying the neuroprotective effects of S. fruticosa infusion and its representative compound rosmarinic acid, which was detected by LC-DAD-ESI-MS/MS. The protective effects of the S. fruticosa infusion (SFINF) and its major substance rosmarinic acid (RA) on amyloid beta 1-42-induced cytotoxicity on SH-SY5Y cells together with p-GSK-3 beta activation were investigated. Their in vitro inhibitory effects against glycogen synthase kinase 3 beta, beta-secretase, and casein kinase 1 delta enzymes were also evaluated.The results showed that treatment with the all tested concentrations, SFINF significantly decreased A beta 1-42-induced cytotoxicity and exhibited promising in vitro glycogen synthase kinase 3 beta inhibitory activity below 10 mu g/mL (IC50 6.52 +/- 1.14 mu g/mL), in addition to beta-secretase inhibition (IC50 86 +/- 2.9 mu g/mL) and casein kinase 1 delta inhibition (IC50 121.57 +/- 4.00). The SFINF (100 mu g/mL and 250 mu g/mL) also activated the expression of p-GSK-3 beta in amyloid beta 1-42 treated SH-SY5Y cells.The outcomes of this study demonstrated that the S. fruticosa infusion possessed activity to prevent amyloid beta 1-42-induced neurotoxicity and provided proof that its mechanism may involve regulation of p-GSK-3 beta protein. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of King Saud University.