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

Abstract

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.

Lycopodium Attenuates Loss of Dopaminergic Neurons by Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson’s Disease

“…However, drugs that are used for cholinesterase inhibitory activity are limited, and possess side effects related to cholinergic stimulation in peripheral tissues and the brain. Many literature reports state that oxidative stress-mediated neuroinflammation could be the major culprit, self-propelling neurodegeneration in Parkinson’s disease [32,33,34]. Hence, the search for novel multi-modal drugs that have neuroprotective, neurorestorative and anti-cholinergic capabilities, along with less side effects, would be promising for the treatment of Parkinson’s disease.…”

Use of Curcumin, a Natural Polyphenol for Targeting Molecular Pathways in Treating Age-Related Neurodegenerative Diseases

“…Sixthly, Cur can inhibit activity of monoamine oxidase (similar to MAO-inhibitor), thus restoring DA levels [ 161 ] and reducing depression [ 162 ]. Seventhly, Cur can protect DA neurons in brain by reducing ROS levels, maintaining mitochondrial functions, and attenuating neuroinflammation via CNB001, a Cur-derived compound [ 163 ] Finally, Cur can inhibit the JNK pathway and prevent dopaminergic neuronal loss via apoptosis [ 163 ] ( Figure 20 ).…”

Recent Updates in Curcumin Pyrazole and Isoxazole Derivatives: Synthesis and Biological Application

“…This may have strong therapeutic potential for dealing of PD. [54] Curcumin phenylpyrazole 7 and cyclohexyl bisphenol have superior biological properties compared with parent compound curcumin. MPTP model of PD was used as anti-inflammatory and anti-apoptotic mediated neuroprotection of pyrazole derivatives of curcumin.…”