Protective Effect of Curcumin and its Combination with Piperine (Bioavailability Enhancer) Against Haloperidol-Associated Neurotoxicity: Cellular and Neurochemical Evidence

Abstract

Long-term treatment with haloperidol is associated with a number of extrapyramidal side effects, particularly the irregular movements of chorionic type. This limitation presents a marked therapeutic challenge. The present study investigates the molecular etiology of haloperidol neurotoxicity and the role of curcumin, a well-known anti-oxidant, in ameliorating these adverse effects. The redox status of haloperidol-treated brains along with NO, TNF-α, NF-kappaB p65 subunit, caspase-3, and monoamine neurotransmitters were measured in the striatum of rat brain. Chronic treatment with haloperidol (5 mg/kg, i.p., 21 days) produced orofacial dyskinetic movements which were coupled with marked increase in oxidative stress parameters, TNF-α, caspase-3 activity in cytoplasmic lysate and active p65 sub unit of NF-kappaB in nuclear lysates of the striatum. Neurochemically, chronic administration of haloperidol resulted in a significant decrease in the levels of norepinephrine, dopamine, and serotonin. The prototype atypical anti-psychotic, clozapine (10 mg/kg, i.p., 21 days) produced mild oxidative stress but did not alter any other parameters. Interestingly, co-administration of curcumin (25 and 50 mg/kg, i.p., 21 days) dose-dependently prevented all the behavioral, cellular, and neurochemical changes associated with the chronic administration of haloperidol. Curcumin per se (50 mg/kg) did not show any side effects. Co-administration of piperine significantly enhanced the effect of curcumin (25 mg/kg) but not of curcumin (50 mg/kg). Collectively, the data indicated the potential of curcumin as an adjunct to haloperidol treatment and provided initial clues to the underlying molecular mechanisms in haloperidol neurotoxicity. This study also provides a rationale for the combination of piperine and curcumin.

Preventive Effect of Curcumin Against Chemotherapy-Induced Side-Effects

“…Curcumin (C 21 H 20 O 6 ) (Figure 1 ) is an active compound from natural plant Curcuma longa L., which is widely used as a coloring and flavoring agent in food industry and a herbal medicine in Asian countries for thousands of years to treat vomiting, headache, diarrhea, etc. Recently, pharmacological studies have revealed that curcumin has strong antioxidative, anti-microbial, anti-inflammatory and anticancer activities ( Bishnoi et al, 2011 ; Wang et al, 2011a , b , 2012 ; Shiau et al, 2012 ; Mendonça et al, 2013 ; Sankrityayan and Majumdar, 2016 ; Dai et al, 2018 ). Growing evidence shows that curcumin is a very safe product to human being ( Shehzad et al, 2013 ).…”

Neuroprotective Activity of Curcumin in Combination with Piperine against Quinolinic Acid Induced Neurodegeneration in Rats

“…Similarly, increased ROS and lipid peroxidation promote DNA-dependent transcription of inflam- The previous reports suggest that QA on intrastriatal administration causes excitotoxicity, oxidative stress, activation of NF-ĸB and p53-induced neurodegeneration. Moreover, the damage in striatal neuron leads to lowering of catecholamine levels (norepinephrine (NE), DA and serotonin), 5-HIAA and increased the level of DOPAC and HVA in the striatum nuclei [15] . Striatal area mainly receives GABAergic neuronal projections and is the most vulnerable in HD; that is why the dysfunction of these neurons is responsible for the development of chorea [16] .…”

“…CMN is a potent antioxidant with reported neuroprotective and anti-inflammatory activity due to its inhibitory effect over COX-2, LOX-5, TNF-α, NF-ĸB, iNOS and P13K/AKT [15] . But the major complication is its very low oral bioavailability; so when piperine (bioavailability enhancer) is co-administered with CMN, it promotes its therapeutic effect.…”

Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future

“…As the key intracellular cysteine protease of the cascade of events associated with apoptosis, both caspase-3 and caspase-7 were activated and significantly upregulated after neural injury. Administration of curcumin significantly and dose-dependently inhibited caspase-3 and caspase-7 levels and exerted antiapoptosis effects [ 29 , 31 , 32 ].…”