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


ÇELİK TOPKARA K. , KILINÇ E., ÇETİNKAYA A., Saylan A., DEMİR Ş.

EUROPEAN JOURNAL OF NEUROSCIENCE, 2021 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2021
  • Doi Number: 10.1111/ejn.15565
  • Title of Journal : EUROPEAN JOURNAL OF NEUROSCIENCE
  • Keywords: Alzheimer's disease, carvacrol, memory, neurotoxicity, oxidative stress, SH-SY5Y cells, MILD COGNITIVE IMPAIRMENT, TRANSGENIC MOUSE MODEL, OXIDATIVE STRESS, CHOLINERGIC NEURONS, LIPID-PEROXIDATION, PROTEIN, NEUROINFLAMMATION, PEPTIDE, THYMOL, MEMORY

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 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.