Therapeutic effects of carvacrol on beta-amyloid-induced impairments in in vitro and in vivo models of Alzheimer's disease

Due to the complex nature of Alzheimer's disease (AD), it is important to investigate agents with multiple effects in the treatment of AD. Carvacrol possesses anti-acetylcholinesterase, anti-oxidant, and neuroprotective properties. We therefore investigated therapeutic effects of carvacrol on cell viability, oxidative stress, and cognitive impairment in A beta 1-42-induced in vitro and in vivo models of AD. SH-SY5Y cells differentiated into neurons by retinoic acid were pretreated with carvacrol or galantamine before A beta 1-42 administration. For in vivo experiments, a rat model of AD was established by bilateral intrahippocampal injection of A beta 1-42. The groups received 1% DMSO, carvacrol, or galantamine intraperitoneally twice a day (morning and afternoon) for 6 days. Cell viability was determined using MTT and LDH tests. Learning and memory functions were assessed using a passive-avoidance test. Oxidant-antioxidant parameters (MDA, H2O2, SOD, and CAT) and Tau, A beta 1-40, and A beta 1-42 peptide levels in in vitro supernatant or in vivo serum and hippocampal samples were measured using ELISA. Carvacrol increased cell viability and exhibited a protective effect against oxidative stress by preventing A beta 1-42-induced cytotoxicity, LDH release, and increments in MDA and H2O2 levels in vitro. Additionally, it improved memory impairment by reversing A beta 1-42-induced changes on passive-avoidance test. Carvacrol ameliorated A beta 1-42-induced increments in MDA and H2O2 levels in in vitro supernatant and in vivo hippocampal samples. However, none of the treatments changed in vitro SOD and Tau-peptide levels, or in vivo serum levels of MDA, H2O2, SOD, CAT, Tau peptide, A beta 1-40, or A beta 1-42. Our results suggest that multi-target pharmacological agent carvacrol may be promising in treatment of AD by preventing beta-amyloid-induced neurotoxicity, oxidative stress, and memory deficits.