Dharmendra Kumar Khatri

Neuroprotective effect of curcumin as evinced by abrogation of rotenone-induced motor deficits, oxidative and mitochondrial dysfunctions in mouse model of Parkinson's disease.

Curcumin, a natural polyphenolic compound extracted from rhizomes of Curcuma longa (turmeric), a plant in the ginger family (Zingiberaceae) has been used worldwide and extensively in Southeast Asia. Curcumin exhibited numerous biological and pharmacological activities including potent antioxidant, cardiovascular disease, anticancer, anti-inflammatory effects and neurodegenerative disorders in cell cultures and animal models. Hence, the present study was designed in order to explore the possible neuroprotective role of curcumin against rotenone induced cognitive impairment, oxidative and mitochondrial dysfunction in mice. Chronic administration of rotenone (1mg/kg i.p.) for a period of three weeks significantly impaired cognitive function (actophotometer, rotarod and open field test), oxidative defense (increased lipid peroxidation, nitrite concentration and decreased activity of superoxide dismutase, catalase and reduced glutathione level) and mitochondrial complex (II and III) enzymes activities as compared to normal control group. Three weeks of curcumin (50, 100 and 200mg/kg, p.o.) treatment significantly improved behavioral alterations, oxidative damage and mitochondrial enzyme complex activities as compared to negative control (rotenone treated) group. Curcumin treated mice also mitigated enhanced acetylcholine esterase enzyme level as compared to negative control group. We found that curcumin restored motor deficits and enhanced the activities of antioxidant enzymes suggesting its antioxidant potential in vivo. The findings of the present study conclude neuroprotective role of curcumin against rotenone induced Parkinsons in mice and offer strong justification for the therapeutic prospective of this compound in the management of PD.

Kinetics of Inhibition of Monoamine Oxidase Using Curcumin and Ellagic Acid.

Background: Curcumin and ellagic are the natural polyphenols having a wide range of pharmacological actions. They have been reported to have their use in various neurological disorders. Objective: This study was aimed to evaluate the effect of curcumin and ellagic acid on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters which are pivotal for neuronal development and function. Materials and Methods: The in vitro effects of these selected polyphenols on MAO activities in mitochondria isolated from rat brains were examined. Brain mitochondria were assayed for MAO type-B (MAO-B) using benzylamine as substrates. Rat brain mitochondrial MAO preparation was used to study the kinetics of enzyme inhibition using double reciprocal Lineweaver–Burk plot. Results: MAO activity was inhibited by curcumin and ellagic acid; however, higher half maximal inhibitory concentrations of curcumin (500.46 nM) and ellagic acid (412.24 nM) were required compared to the known MAO-B inhibitor selegiline. It is observed that the curcumin and ellagic acid inhibit the MAO activity with both the competitive and noncompetitive type of inhibitions. Conclusions: Curcumin and ellagic acid can be considered a possible source of MAO inhibitor used in the treatment of Parkinsons and other neurological disorders. SUMMARY Monoamine oxidase (MAO) is involved in a variety of neurological disorders including Parkinsons disease (PD) Curcumin and ellagic acid inhibit the monoamine oxidase activity Ellagic acid revealed more potent MAO type-B (MAO-B) inhibitory activity than curcumin Kinetic studies of MAO inhibition using different concentrations of curcumin and ellagic acid were plotted as double reciprocal Lineweaver–Burk plot The mode of inhibition of both compounds toward MAO-B is mixed (competitive and uncompetitive) type of inhibition with both the competitive and noncompetitive type of inhibitions. Abbreviations used: MAO: Monoamine oxidase, IC50: Higher half maximal inhibitory concentrations, PD: Parkinsons disease, LB: Lewy bodies, SNpc: Substantia nigra pars compacta, ROS: Reactive oxygen species, SG: Selegiline, DMC: demethoxycurcumin, BDMC: Bisdemethoxycurcumin. Archana Ramesh Juvekar

Erratum to: Propensity of Hyoscyamus Niger seeds methanolic extract to allay stereotaxically rotenone-induced Parkinson’s disease symptoms in rats

Hyoscyamus niger (L), of Solanaceae family, commonly known as henbane is used in the traditional Indian medical system of Ayurveda and Chinese system of medicine for the nervous system disorders. We have evaluated neuroprotective potential of methanol extract of Hyoscymus Niger (MHN) seeds in stereotaxically induced rotenone model of Parkinson’s disease in rats. MHN was characterized employing HPLC-UV and LCMS. The extract showed presence of L-dopa with significant inhibition in DPPH, ABTS in-vitro assay and monoamine oxidase activity. Male Wistar rats were pretreated with MHN (125, 250, 500 mg/kg body weight p.o.) once daily for 7 days and subjected to unilateral intrastriatal injection of rotenone (8 μg in 0.1 % ascorbic acid in normal saline). Three weeks after rotenone infusion, rats were tested for neurobehavioral activity and were sacrificed for estimation of lipid peroxidation (TBARS), total glutathione (GSH) content, and activity of antioxidant enzymes glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in brain homogenates. Administration of the MHN (containing L-DOPA) significantly attenuated motor disabilities (actophotometer, rotarod and Morris water maze test). Rat treated with rotenone showed reduced levels of thiobarbituric acid reactive substance (TBARS) and increased level of GSH content and antioxidants enzymes activities (GPX, SOD and CAT) in the MHN treated PD rat. The findings suggest that MHN is a potential drug for treating oxidative damage, physiological abnormalities and is effective in neuroprotection in experimental models of PD.