Demethoxycurcumin, a Natural Derivative of Curcumin Abrogates Rotenone-induced Dopamine Depletion and Motor Deficits by Its Antioxidative and Anti-inflammatory Properties in Parkinsonian Rats

Muthu Ramkumar; Srinivasagam Rajasankar; Veerapan Venkatesh Gobi; Udaiyappan Janakiraman; Thamilarasan Manivasagam; Arokiasamy Justin Thenmozhi; Musthafa Mohamed Essa; Ranganathan Chidambaram; Saravana Babu Chidambaram; Giles J Guillemin

doi:10.4103/pm.pm_113_17

Demethoxycurcumin, a Natural Derivative of Curcumin Abrogates Rotenone-induced Dopamine Depletion and Motor Deficits by Its Antioxidative and Anti-inflammatory Properties in Parkinsonian Rats

Pharmacogn Mag. 2018 Jan-Mar;14(53):9-16. doi: 10.4103/pm.pm_113_17. Epub 2018 Feb 20.

Affiliations

¹ Department of Anatomy, Bharath University, Selaiyur, Chennai, India.
² Department of Anatomy, Velammal Medical College and Hospital, Madurai, India.
³ Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu, India.
⁴ Department of Food Science and Nutrition, CAMS, Sultan Qaboos University, Muscat.
⁵ Ageing and Dementia Research Group, Sultan Qaboos University, Muscat, Oman.
⁶ Food and Brain Research Foundation, Chennai, Tamil Nadu, India.
⁷ Department of Radiology, Sri Lakshminarayana Institute of Medical Sciences, Puducherry, India.
⁸ Department of Pharmacology, JSS College of Pharmacy, JSS University, SS Nagar, Mysore, Karnataka, India.
⁹ Neuroinflammation Group, Department of Biomedical Research, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.

Abstract

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder (NDD) associated with the loss of dopaminergic neurons in the substantia nigra and subsequently has an effect on motor function and coordination. The pathology of PD is multifactorial, in which neuroinflammation and oxidative damage are the two of the main protagonists.

Objectives: The present study aims to assess the potential antioxidant and anti-inflammatory effects of demethoxycurcumin (DMC), a natural derivative of curcumin, against rotenone-induced PD in rats.

Materials and methods: Rats were randomized and divided into six groups: control, rotenone (0.5 mg/kg/day, intraperitoneal in sunflower oil) treated for 7 days, rotenone and DMC (5, 10, and 20 mg/kg b.w) cotreated, and DMC (20 mg/kg b.w) alone treated groups.

Results: Based on the dopamine concentration and biochemical estimations, the effective dose of DMC was selected and the chronic study was performed. At the end of the experimental period, behavioral studies and protein expression patterns of inflammatory markers were analyzed. Rotenone treatment led to motor dysfunctions, neurochemical deficits, and oxidative stress and enhanced expressions of inflammatory markers, whereas oral administration of DMC attenuated all the above.

Conclusion: Even though further research is needed to prove its efficacy in clinical trial, the results of our study showed that DMC may offer a promising and new therapeutic lead for the treatment of NDDs including PD.

Summary: Curcumin and their derivatives have been shown to be potent neuroprotective effectDemethoxycurcumin (DMC) amolerated the rotenone induced behavioural alterationsDMC abrogated the rotenone induced dopamine deficitsDMC attenuated the rotenone induced oxidative stressDMC diminished the rotenone mediated inflammation. Abbreviations used: COX-2: Cyclooxygenase-2; DA: Dopamine; DMC: Demethoxycurcumin; DMRT: Duncan's multiple range test; GSH: Reduced glutathione; GPx: Glutathione peroxidase; IL-1 β: Interleukin-1 β; IL-6: Interleukin-6; iNOS: Inducible nitric oxide synthase; PD: Parkinson's disease; SN: Substantia nigra; SOD: Superoxide dismutase; TBARS: Thiobarbituric acid reactive substances; TNF-α: Tumor necrosis factor-α.

Keywords: Demethoxycurcumin; dopamine; neurodegenerative disease; neuroinflammation; oxidative stress.