Neuroprotective Effects of Farnesene Against Hydrogen Peroxide-Induced Neurotoxicity In vitro

Abstract

Oxidative stress is highly damaging to cellular macromolecules and is also considered a main cause of the loss and impairment of neurons in several neurodegenerative disorders. Recent reports indicate that farnesene (FNS), an acyclic sesquiterpene, has antioxidant properties. However, little is known about the effects of FNS on oxidative stress-induced neurotoxicity. We used hydrogen peroxide (H2O2) exposure for 6 h to model oxidative stress. Therefore, this experimental design allowed us to explore the neuroprotective potential of different FNS isomers (α-FNS and β-FNS) and their mixture (Mix-FNS) in H2O2-induced toxicity in newborn rat cerebral cortex cell cultures for the first time. For this aim, both MTT and lactate dehydrogenase assays were carried out to evaluate cell viability. Total antioxidant capacity (TAC) and total oxidative stress (TOS) parameters were used to assess oxidative alterations. In addition to determining of 8-hydroxy-2-deoxyguanosine (8-OH-dG) levels in vitro, the comet assay was also performed for measuring the resistance of neuronal DNA to H2O2-induced challenge. Our results showed that survival and TAC levels of the cells decreased, while TOS, 8-OH-dG levels and the mean values of the total scores of cells showing DNA damage (comet assay) increased in the group treated with H2O2 alone. But pretreatment of FNS suppressed the cytotoxicity, genotoxicity and oxidative stress, which were increased by H2O2 in clear type of isomers and applied concentration-dependent manners. The order of antioxidant effectiveness for modulating H2O2-induced oxidative stress-based neurotoxicity and genotoxicity is as β-FNS > Mix-FNS > α-FNS.

Biologically Active Compounds from Hops and Prospects for Their Use

“…The acyclic sesquiterpene β‐farnesene, a substance characteristic for hop varieties genetically related to Saaz hops, was also tested in vitro for its antioxidant properties. Testing on human blood tissue (Celik and others ) showed a slight increase in antioxidant capacity after 24 h of exposure to farnesene (10 to 25 μg/mL) and application of farnesene to rat cerebral cortex neurons showed a reduction in H 2 O 2 ‐induced oxidative stress, suggesting the possibility of its use for the prevention of certain neurodegenerative diseases (Turkez and others ). Similar effects, in this case relating to a reduction in 1,2‐dimethylhydrazine‐induced oxidative stress in rat colon cells was also shown for farnesol, which was able to potentiate the activity of antioxidant enzymes at a level of 40 mg/kg b.w.…”

Protective effects of cyclosativene on H2O2-induced injury in cultured rat primary cerebral cortex cells

“…In addition, huperzine A showed protective activity against H 2 O 2 -induced damage in SHSY5Y cells (Tang et al 2005). Moreover, Turkez et al (2013) found that a-FNS and b-FNS, naturel sesquiterpenic compounds, were capable of protecting against H 2 O 2 -induced cytotoxicity and oxidative DNA damage in cultured rat primary cortical neuronal cells. Since, high levels of exogenously generated H 2 O 2 induced cell death via extensive DNA damage (Panieri et al 2013) and Comet formations with almost all DNA in the tail were often referred to as 'hedgehog' Comets and are widely assumed to represent apoptotic cells (Lorenzo et al Fig.…”

“…They have long been investigated for biological activities; anticarcinogenic (Afoulous et al 2013), antimicrobial (Wang et al 2013), antifungal (Kundu et al 2013), antiinflammatory (Wang et al 2013), more recently, and antioxidant activities (Abolaji et al 2013). Also it was reported that sesquiterpenes could provide protection against H 2 O 2 damage in many cell lines (Tang et al 2005;Umemura et al 2008;Gan et al 2009;Turkez et al 2013). Cyclosativene (CSV) is a tetracyclic sesquiterpene (Fig.…”

Morroniside protects SK-N-SH human neuroblastoma cells against H2O2-induced damage

“…Usually, antioxidants, especially those derived from natural sources, have many therapeutic applications (27,28). Morroniside is a constituent of C. officinalis , a traditional Chinese medicine (29), and has demonstrated protective effects against cerebral ischemic damage (15), indicating a potential role of morroniside on restoring injured neurons.…”