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 Aβ1-42-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 Aβ1-42 administration. For in vivo experiments, a rat model of AD was established by bilateral intrahippocampal injection of Aβ1-42. 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, H 2 O 2 , SOD, and CAT) and Tau, Aβ1-40, and Aβ1-42 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 Aβ1-42-induced cytotoxicity, LDH release, and increments in MDA and H 2 O 2 levels in vitro. Additionally, it improved memory impairment by reversing Aβ1-42-induced changes on passive-avoidance test. Carvacrol ameliorated Aβ1-42-induced increments in MDA and H 2 O 2 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, H 2 O 2 , SOD, CAT, Tau peptide, Aβ1-40, or Aβ1-42. 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.