Abstract
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 six 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, 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 H2O2 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 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, 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.
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