Neuroprotective Effect of CNB-001, a Novel Pyrazole Derivative of Curcumin on Biochemical and Apoptotic Markers Against Rotenone-Induced SK-N-SH Cellular Model of Parkinson’s Disease

Jayaraj, Richard L.; Tamilselvam, Kuppusamy; Manivasagam, Thamilarasan; Elangovan, Namasivayam

doi:10.1007/s12031-013-0075-8

Cited by 68 publications

(51 citation statements)

References 30 publications

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“…Our findings are also similar to those reported during apoptosis mediated cell death in SN of PD [44]. Moreover CNB-001 protected SK-N-SH neuroblastoma against rotenone toxicity by maintaining mitochondrial membrane potential through inhibition of proapoptotic factors [13]. These results confirm the protective action of CNB-001 on mitochondria, thus alleviating neuronal pathology.…”

Section: Discussionsupporting

confidence: 91%

“…Moreover depletion of GSH and GPx might be an early mechanism involved in initiation of oxidative stress and possibly provides sensitivity to DA-ergic neurons against toxin [33]. Previous reports from our lab showed that CNB-001 protected SK-N-SH cells against rotenone toxicity by inhibiting accumulation of intracellular ROS formation [13]. Thus, neuroprotective activity of CNB-001 may be partially due to the regulation of antioxidant enzymes which is depleted upon MPTP treatment.…”

Section: Discussionmentioning

confidence: 99%

“…These hindrances were surmounted by CNB-001[4-((1E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1-phenyl-1H-pyrazoyl-3-yl) vinyl)-2-methoxy-phenol], a novel hybrid molecule synthesized from curcumin, and cyclohexyl bisphenol A (CBA), a molecule with neurotrophic activity [11]. Further, CNB-001 was shown to protect against excitotoxicity, glucose-starvation assay [11], β -amyloid toxicity [12] and to also exhibit strong antioxidant and antiapoptotic properties [13]. Additionally, CNB-001 has been shown to possess lower EC50 values and superior anti-inflammatory properties compared to its parental compounds [11].…”

Section: Introductionmentioning

confidence: 99%

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CNB-001 a Novel Curcumin Derivative, Guards Dopamine Neurons in MPTP Model of Parkinson’s Disease

Jayaraj

Elangovan

Krishnan

et al. 2014

BioMed Research International

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Copious experimental and postmortem studies have shown that oxidative stress mediated degeneration of nigrostriatal dopaminergic neurons underlies Parkinson's disease (PD) pathology. CNB-001, a novel pyrazole derivative of curcumin, has recently been reported to possess various neuroprotective properties. This study was designed to investigate the neuroprotective mechanism of CNB-001 in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent model of PD. Administration of MPTP (30 mg/kg for four consecutive days) exacerbated oxidative stress and motor impairment and reduced tyrosine hydroxylase (TH), dopamine transporter, and vesicular monoamine transporter 2 (VMAT2) expressions. Moreover, MPTP induced ultrastructural changes such as distorted cristae and mitochondrial enlargement in substantia nigra and striatum region. Pretreatment with CNB-001 (24 mg/kg) not only ameliorated behavioral anomalies but also synergistically enhanced monoamine transporter expressions and cosseted mitochondria by virtue of its antioxidant action. These findings support the neuroprotective property of CNB-001 which may have strong therapeutic potential for treatment of PD.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CNB-001 a Novel Curcumin Derivative, Guards Dopamine Neurons in MPTP Model of Parkinson’s Disease

Jayaraj

Elangovan

Krishnan

et al. 2014

BioMed Research International

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“…Orange–red fluorescence is emited by polarized mitochondrion, and depolarized mitochondrion emits green fluorescence. Spectrofluorometer is used to measure the fluorescent intensity at 535 nm [27]. …”

Section: Methodsmentioning

confidence: 99%

Neuroprotective effect of Demethoxycurcumin, a natural derivative of Curcumin on rotenone induced neurotoxicity in SH-SY 5Y Neuroblastoma cells

Ramkumar

Rajasankar

Gobi

et al. 2017

BMC Complement Altern Med

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BackgroundMitochondrial dysfunction and oxidative stress are the main toxic events leading to dopaminergic neuronal death in Parkinson’s disease (PD) and identified as vital objective for therapeutic intercession. This study investigated the neuro-protective effects of the demethoxycurcumin (DMC), a derivative of curcumin against rotenone induced neurotoxicity.MethodsSH-SY5Y neuroblastoma cells are divided into four experimental groups: untreated cells, cells incubated with rotenone (100 nM), cells treated with DMC (50 nM) + rotenone (100 nM) and DMC alone treated. 24 h after treatment with rotenone and 28 h after treatment with DMC, cell viability was assessed using the MTT assay, and levels of ROS and MMP, plus expression of apoptotic protein were analysed.ResultsRotenone induced cell death in SH-SY5Y cells was significantly reduced by DMC pretreatment in a dose-dependent manner, indicating the potent neuroprotective effects of DMC. Rotenone treatment significantly increases the levels of ROS, loss of MMP, release of Cyt-c and expression of pro-apoptotic markers and decreases the expression of anti-apoptotic markers.ConclusionsEven though the results of the present study indicated that the DMC may serve as a potent therapeutic agent particularly for the treatment of neurodegenerative diseases like PD, further pre-clinical and clinical studies are required.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-017-1720-5) contains supplementary material, which is available to authorized users.

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“…Insilico analysis done in our lab (data not shown) also showed that CNB-001 is non-toxic, has good ADMET properties and protected SK-N-SH cells in vitro against rotenone toxicity. [36] Therefore, this compound is tested for antioxidant and DNA protecting activity, which stands as a baseline property for a drug. It is believed that the present work would enhance and highlight the potentiality of CNB-001 for further drug targeted studies.…”

Section: Discussionmentioning

confidence: 99%

In vitro antioxidant potential and deoxyribonucleic acid protecting activity of CNB-001, a novel pyrazole derivative of curcumin

Jayaraj

Elangovan

2014

Chron Young Sci

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Background: Free radicals are underpinned to initiate cascade of toxic events leading to oxidative stress and resultant cell death in many neurodegenerative disorders. Now-a-days antioxidants have become mandatory in the treatment of various diseases apart from the drug's modes of action. CNB-001, a novel hybrid molecule synthesized by combining curcumin and cyclohexyl bisphenol A is known to possess various biological activities, but the antioxidative property of the compound has not yet been elucidated. Aim: The present study is aimed to analyze various free radicals scavenging by employing in vitro antioxidant assays and to evaluate the deoxyribonucleic acid (DNA) protecting the ability of CNB-001 against hydroxyl radicals. Materials and methods: The in vitro antioxidant potential of CNB-001 was evaluated by analyzing its ability to scavenge DPPH, ABTS, nitric oxide, superoxide, hydrogen peroxide, superoxide anion, hydroxyl, hydrogen peroxide radicals and reducing power using spectroscopic method. The DNA protecting activity of CNB-001 was also evaluated on pUC19 plasmid DNA subjected to hydroxyl radicals using standard agarose gel electrophoresis. Results: From the assays, it was observed that CNB-001 scavenged free radicals effectively in a dose dependent manner. CNB-001 scavenged 2,2-diphenyl-1-picrylhydrazyl (IC50 = 44.99 µg/ml), 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (IC50 = 17.99 µg/ml), nitric oxide (IC50 = 1.36 µg/ml), superoxide radical (IC50 = 77.17 µg/ml), hydrogen peroxide (IC50 = 492.7 µg/ml), superoxide (IC50 = 36.92 µg/ml) and hydroxyl (IC50 = 456.5 µg/ml) radicals effectively and the reducing power was found to be 11.53 µg/ml. CNB-001 showed considerable protecting activity against plasmid DNA (pUC19) strand scission by •OH at dose dependent manner. Conclusion: Results from these assays concluded that CNB-001 has a good antioxidant potential by reducing reactive oxygen and reactive nitrogen radicals and it showed significant protecting activity against DNA scission by hydroxyl radicals. Hence, CNB-001 can be further developed as potential drug for free radical induced neurodegenerative disorders.

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Neuroprotective Effect of CNB-001, a Novel Pyrazole Derivative of Curcumin on Biochemical and Apoptotic Markers Against Rotenone-Induced SK-N-SH Cellular Model of Parkinson’s Disease

Cited by 68 publications

References 30 publications

CNB-001 a Novel Curcumin Derivative, Guards Dopamine Neurons in MPTP Model of Parkinson’s Disease

CNB-001 a Novel Curcumin Derivative, Guards Dopamine Neurons in MPTP Model of Parkinson’s Disease

Neuroprotective effect of Demethoxycurcumin, a natural derivative of Curcumin on rotenone induced neurotoxicity in SH-SY 5Y Neuroblastoma cells

In vitro antioxidant potential and deoxyribonucleic acid protecting activity of CNB-001, a novel pyrazole derivative of curcumin

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