Abstract
BackgroundAlzheimer’s disease is a neurodegenerative disease, characterized by progressive decline in memory and cognitive functions, that results from loss of neurons in the brain. Amyloid beta (Aβ) protein and oxidative stress are major contributors to Alzheimer’s disease, therefore, protecting neuronal cells against Aβ-induced toxicity and oxidative stress might form an effective approach for treatment of this disease. 3,5,4′-trihydroxy-6,7,3′-trimethoxyflavone (TTF) is a flavonoid we have purified from the plant Achillea fragrantissima; and the present study examined, for the first time, the effects of this compound on Aβ-toxicity to neuronal cells.MethodsVarious chromatographic techniques were used to isolate TTF from the plant Achillea fragrantissima, and an N2a neuroblastoma cell line was used to study its activities. The cellular levels of total and phosphorylated stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and of total and phosphorylated extracellular signal-regulated kinase (ERK 1/2) were determined by enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) levels were measured by using 2′,7′-dichlorofluorescein diacetate (DCF-DA). Cytotoxicity and cell viability were assessed by using lactate dehydrogenase (LDH) activity in cell-conditioned media, or by crystal violet cell staining, respectively.ResultsTTF prevented the Aβ-induced death of neurons and attenuated the intracellular accumulation of ROS following treatment of these cells with Aβ. TTF also inhibited the Aβ-induced phosphorylation of the signaling proteins SAPK/JNK and ERK 1/2, which belong to the mitogen-activated protein kinase (MAPK) family.ConclusionTTF should be studied further as a potential therapeutic means for the treatment of Alzheimer’s disease.
Highlights
Alzheimer’s disease is a neurodegenerative disease, characterized by progressive decline in memory and cognitive functions, that results from loss of neurons in the brain
We have shown that 3,5,4′-trihydroxy-6,7,3′-trimethoxyflavone (TTF), a flavonoid that we have isolated from Achillea fragrantissima, prevented the hydrogen peroxide (H2O2)-induced death of astrocytes, and inhibited the phosphorylation of cell-signaling proteins that belong to the mitogen-activated protein kinase (MAPK) family [14]
Chemicals and reagents Aβ25–35, crystal violet, and 2′,7′-dichlorofluorescein diacetate (DCF-DA) were purchased from Sigma Chemical Co. (St Louis, MO, USA); Dulbecco’s modified Eagle’s medium (DMEM) and Opti-MEM were purchased from Gibco (Paisley, UK); glutamine, antibiotics (10,000 IU/ mL penicillin and 10,000 μg/mL streptomycin), fetal bovine serum (FBS) and trypin-EDTA were purchased from Biological Industries (Beit Haemek, Israel); dimethyl sulfoxide (DMSO) was obtained from Applichem (Darmstadt, Germany)
Summary
Alzheimer’s disease is a neurodegenerative disease, characterized by progressive decline in memory and cognitive functions, that results from loss of neurons in the brain. Flavonoids are phytochemicals that exhibit a broad range of biological functions, including anti-inflammatory, antioxidative and neuroprotective activities [6,7,8,9,10,11]. In light of these activities, they seem to Telerman et al BMC Complementary and Alternative Medicine (2017) 17:332 be promising candidates for development as drugs for treatment of neurodegenerative diseases [8, 12, 13]. TTF scavenges free radicals and mitigates intracellular accumulation of ROS following treatment of these cells with H2O2 or with the peroxyl radicals-generating molecule 2,2′-azobis(amidinopropane) (ABAP) [14]; it is characterized by a relatively low polarity and low molecular weight of 360.3, it might cross the blood-brain barrier and could be used for further investigations in cellular and animal models of AD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
