In vitro biological activity of Salvia fruticosa Mill. infusion against amyloid β-peptide-induced toxicity and inhibition of GSK-3β, CK-1δ, and BACE-1 enzymes relevant to Alzheimer's disease

摘要

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 β activation were investigated. Their in vitro inhibitory effects against glycogen synthase kinase 3 β , β -secretase, and casein kinase 1 δ enzymes were also evaluated. The results showed that treatment with the all tested concentrations, SFINF significantly decreased A β 1–42-induced cytotoxicity and exhibited promising in vitro glycogen synthase kinase 3 β inhibitory activity below 10?μg/mL (IC 50 6.52?±?1.14?μg/mL), in addition to β -secretase inhibition (IC 50 86?±?2.9?μg/mL) and casein kinase 1 δ inhibition (IC 50 121.57?±?4.00). The SFINF (100?μg/mL and 250?μg/mL) also activated the expression of p-GSK-3 β 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 β protein.