Sesamin Modulates Tyrosine Hydroxylase, Superoxide Dismutase, Catalase, Inducible No Synthase and Interleukin‐6 Expression in Dopaminergic Cells Under Mpp+‐Induced Oxidative Stress

Abstract

Oxidative stress is regarded as a mediator of nerve cell death in several neurodegenerative disorders, such as Parkinson's disease. Sesamin, a lignan mainly found in sesame oil, is currently under study for its anti-oxidative and possible neuroprotective properties. We used 1-methyl-4-phenyl-pyridine (MPP+) ion, the active metabolite of the potent parkinsonism-causing toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, to produce oxidative stress and neurodegeneration in neuronal PC12 cells, which express dopamine, as well as neurofilaments. Our results show that picomolar doses of sesamin protected neuronal PC12 cells from MPP+-induced cellular death, as revealed by colorimetric measurements and production of reactive oxygen species. We also demonstrated that sesamin acted by rescuing tyrosine hydroxylase levels from MPP+-induced depletion. Sesamin, however, did not modulate dopamine transporter levels, and estrogen receptor-alpha and -beta protein expression. By examining several parameters of cell distress, we found that sesamin also elicited a strong increase in superoxide dismutase activity as well as protein expression and decreased catalase activity and the MPP+ stimulated inducible nitric oxide synthase protein expression, in neuronal PC12 cells. Finally, sesamin possessed significant anti-inflammatory properties, as disclosed by its potential to reduce MPP+-induced interleukin-6 mRNA levels in microglia. From these studies, we determined the importance of the lignan sesamin as a neuroprotective molecule and its possible role in complementary and/or preventive therapies of neurodegenerative diseases.

Neuroprotective Effect of Sesame Seed Oil in 6-Hydroxydopamine Induced Neurotoxicity in Mice Model: Cellular, Biochemical and Neurochemical Evidence

“…Our results indicate that SO restored the MnSOD protein expression in lesion?SO group and the elevated MnSOD level as compared with lesion demonstrates that SO enhances the ability of SOD to eliminate superoxide radicals formed during 6-OHDA induced oxidative stress. Lahaie-Collins et al [16] reported similar finding that sesamin modulates superoxide dismutase and catalase in dopaminergic cells under 1-methyl-4-phenylpyridinium (MPP? )-induced oxidative stress.…”

“…SO in comparison to other dietary oils such as groundnut, canola and sunflower oil depicted better protection against increased blood pressure, hyperlipidemea and LPO by increasing enzymatic and non-enzymatic antioxidants [14]. Sesamin, sesamolin and tocopherols are powerful antioxidants in SO, and have been reported to possess a broad spectrum of pharmacological effects including neuroprotective, anti-inflammatory, antihypertensive and antimutagenic [15][16][17]. Sesamin and sesamolin have been shown inhibitory effect on LPS-activated p38 mitogen activated protein kinase (MAPK) and nuclear factor kB (NF-kB) activation in microglial cells [18].…”

Transforming growth factor-β1 acts via TβR-I on microglia to protect against MPP+-induced dopaminergic neuronal loss

“…In addition, MPP + induces marked increases in IL-6, IL-1b and TNF-a mRNA levels and protein concentrations in N9 microglial cells (Bournival et al, 2012;Lahaie-Collins et al, 2008), suggesting a direct activation of microglia by MPP + . Here we provide further evidence showing that MPP + can directly induce microglial inflammatory response.…”

Anti-Parkinsonian drug discovery from herbal medicines: What have we got from neurotoxic models?

“…Salvianic acid A and salvianolic acid B from Salvia miltiorrhiza have been shown to be effective on 6-OHDA or MPP + toxicity in vitro Tian et al, 2008). Sesamin from Sesamum indicum or Acanthopanax senticosus has reported to antagonize MPP + toxicity in vitro (Lahaie-Collins et al, 2008) and prevented loss of DA cells, bradykinesia and depression in rotenone model (Fujikawa et al, 2005a).…”