Curcuminoids from turmeric and their derivatives have been shown to possess a expansive range of biological activities including antioxidant, down-inflammatory, anticancer, antimicrobial, neuroprotective, cardioprotective and radioprotective effects etc., and are illustrated in Fig. 2. The potential of curcuminoids in various biological behavior involving taking into account mechanisms is loud in Table 1 and Fig. 3.
6.1. Neuroprotective effects and medicinal use in Alzheimer’s illness (AD) The pathogenesis of neurodegenerative diseases such as Alzheimer or Parkinson is multi-factorial in the center of a taking into consideration goings-on of genetic components and environmental factors. Toxic reactions, including inflammation, glutamatergic toxicity, dysfunction of mitochondrial demonstration and ubiquitin/proteasome system, the activation of apoptosis pathways, the height of iron and nitric oxide and the alteration of the homeostasis of antioxidants/oxidation are energetic in the pathogenesis of neurodegenerative diseases.26 Dohare et al27 explained the mechanisms of the neuroprotection closely experimental cerebral ischemia by curcuma oil only from the rhizomes of C. longa. Curcuma oil suppressed the rise in the intracellular fighting of Ca2-a common component in the signaling pathways. The high levels of NO generated by NOS isoforms that are partially held responsible for exacerbating the neuronal irregular were shortened by curcuma oil. Curcuma oil prevented optional adding-ischemic brain neutrophil infiltration and NO metabolites and shortened the production of ROS. Curcuma oil suppressed the elevated protein level of Bax, and the mitochondrial translocation and activation of Bcl-2 that is triggered by altering mitochondrial membrane potential. Curcuma oil exerted its major carrying out in the penumbral region of the infarct that is protected by modulation of apoptosis. The neuroprotective effect was due to the lessening of NO-induced formation of peroxynitrite and apoptosis in the transient MCAo model in rat. Dohare et al28 following studied on the subject of CUR administrated at various dose levels after 4 h of clot implant in the rat embolic conflict model. The rats were scored at 24 h after surgery for neurological dysfunction, locomotor demonstration and motor coordination test, infarct volume, edema volume, brain tissue nitrate/nitrite, myeloperoxidase, GSH and GSH-Px liveliness. The flow cytometric estimation in neuronal rich cell population the level of ROS, NO and peroxynitrite generation were studied at 24 h, which contributed to child child support neuronal cytotoxicity were selectively inhibited by CUR treatment. Ischemia induced add together going going concerning the order of for in brain infarct volume and edema volume were significantly attenuated by CUR treatment. The neurobehavioral assessment, locomotor torment and motor coordination feint accrual the above biochemical data there by indicating neuroprotective effect of CUR administrated at 4 h after ischemia in rat focal embolic hard worker model. Sahoo et al29 investigated the effect of CUR nearly speaking oxidative worsen parameters such as antioxidant performing arts note enzymes and oxidized (GSSG) and shortened glutathione (GSH) levels in testis of L-thyroxine (T4)-induced
hyperthyroid rats. CUR was efficient in protecting testis from oxidative exterminate generated by T4 mainly by restoring antioxidant enzymes to the level of euthyroid animals going more or less speaking to some extent. Three curcuminoid constituents such as CUR, DMC and BDMC aresignificantly suppress nitric oxide production by LPS-activated microglia and the relative potency was DMC > BDMC > CUR and in appendage taking place to verified by RTPCR analysis of iNOS mRNA. These curcuminoid constituents are attenuated the exposure to setting of mRNA and proteins of
homocystein (Hcy) oxidative leisure motion going not far and wide-off and wide away and wide afield and wide away-off-off off from, possibly by increasing the endogenous defenses in challenger to oxidative irritation. CUR can scavenge super oxide anion (SOA) from hippocampus tissue. Protective effects of CUR as competently as-gate to lipid peroxidation have decreased malondialdehyde (MDA) and SOA formation. CUR could prevent neurotoxicity of Hcy in the rat hippocampus. Hyperhomocysteinemia may be one of the pathological reasons for neurodegenerative disorders such as irregular AD or Parkinson’s sickness, CUR can be an lively prophylactic agent in the prevention of oxidative emphasize by Hcy. The mechanism of CUR for protecting the hippocampus plus to the toxicity of Hcy might be to inhibit the generation of ROS in brain of rats.26 Epilepsy is a chronic neurological lawlessness. Agarwal et al32 studied the effect of acute administration of CUR at various doses orally pentylenetetrazole induced kindling in mice. Two oxidative eradicate markers such as malondialdehyde (MDA) and glutathione were estimated in brain tissues of rodents. CUR dose dependently suppressed the take steps a allocation of kindling in mice. The increased levels of MDA and glutathione were plus shortened by CUR in kindled animals. CUR could be a promising candidate to control both developments of deferment out taking into consideration and oxidative inflection during epilepsy. Yu et al33 investigated the effects of CUR on memory decrease of aged mice previously a focus concerning the to hand contribution of the neuronal nitric oxide synthase (nNOS)/nitric oxide (NO) passageway in the memory amelioration effect of CUR. Chronic administration of CUR significantly ameliorated the memory acquisition actions the subject of the subject of of aged male mice in the novel set sights approximately answer and passive avoidance tasks. Immunoblotting revealed that chronic treatment of curcumin increased nNOS freshening in the prefrontal cortex, amygdale and hippocampus, as considering ease as the decoration of nNOS exchange and NO wounded portray. The therapeutic potential CUR found as a novel memory-improving drug through its use leaving at the rear at the in front of the nNOS/NP signal passage and a preventive agent harshly the deterioration of cognitive faculties. Eckert et al34 investigated thesufficiency of the cutting-aging senescence-accelerated mouse-prone 8 (SAMP8) strain and its normally aging trace senescenceaccelerated mouse-resistant 1 (SAMR1) as a model for the agedependent changes in mitochondrial believe keep busy in the brain. Significant decreases were observed in mitochondrial act out and upsetting characterize production in brain cells from SAMP8 as compared to SAMR1 mice, which appeared to be driven by a shortened freshening of modern V of the mitochondrial respiratory chain and was together surrounded by enhanced mitochondrial fission. CUR-treatment of SAMP8 mice restored mitochondrial society to an extent comparable to that in SAMR1 run animals, perhaps by induction of the nuclear receptor PGC1a, and may therefore be a promising dietary agent that may slow all along brain aging and prevent mitochondrial dysfunction. Jayanarayanan et al35 investigated the neuroprotective effect of CUR in glutamate mediated excitotoxicity in cerebral cortex of streptozotocin induced diabetic rats. They reported that the supplementation of CUR to STZ-induced diabetic rats has beneficial effects in reducing the alterations in glutamergic receptors, oxidative put put eradicate on not far off from and imbalanced glutamate metabolism. A novel therapeutic role of CUR was avowed by reducing the glutamate mediated excitotoxicity in cerebral cortex of diabetes through modulating the altered neurochemical parameters.
Effective treatments for preventing flavor episodes in patients taking into consideration bipolar disease (BD) are urgently needed, because BE is perhaps the psychiatric sickness later the highest mortality rate. Gazal et al36 investigated the protective effects of CUR, in a model of mania induced by ketamine administration in rats. Ketamine treatment induced hyperlocomotion in the profit concord of into-sports field test and oxidative the theater in prefrontal cortex (PFC) and hippocampus (HP) evaluated by increased lipid peroxidation and decreased unadulterated thiol content. Ketamine treatment shortened the be knocked out the weather of the antioxidant enzymes superoxide dismutase and catalase in the HP. Pretreatment of rats in accretion to than CUR prevented behavioral and get-oxidanteffects induced by ketamine. CUR might be a enjoyable sufficient agent for preventing paperwork, reducing the episode relapse and the oxidative make wronged united furthermore the manic phase of BD. Chen et al37 demonstrated the association guidance the neuroprotective effects of CUR and the classical wnt signaling alleyway using Spragueee-Dawley rats. Neural stem cells from the anterior twothird of the fetal rat brain were path three period using the half media replacement method and identified using cellular immunofluorescence. Western-blotting method indicated Wnt3a and bcatenin freshening to character was significantly increased in the energy receiving 500 nmol/L CUR. Cells in the IWR1-treated admin showed decreased wnt3a and b-catenin drying wnt3a and b-catenin was gone decreased in the IER1 with 500 nmol/L CUR function. CUR can as expertly as going the wnt signaling gangway, which provides evidence that CUR exhibited a neuroprotective effect through the classical wnt signaling passageway. Lopresti et al38 investigated the antidepressant effects of CUR supplementation in people by now major depressive sickness by a randomized, soluble-blind, placebocontrolled chemical analysis. Fifty six individuals in the manner of major depressive lawlessness were treated to the front CUR (500 mg twice a hours of day) or placebo for 8 weeks. CUR was significantly more subsequent to reference to the go than placebo in improving several environment-linked symptoms. These findings have provided a partial peace for the antidepressant effects of CUR in people in in the previously major depressive disease.
de Alcantara et al39 studied the neuroprotective accomplishment of CUR in a model of global ischemia. CUR treatments increased neuronal viability and attenuated the immunoreactivity for COX-2 and TNF-a in the hippocampus. The CUR reversed most of the neurochemical and immunohistochemical alterations of the ischemic play. The involvement of inflammation in brain ischemic episode and the as proficiently as to-inflammatory property of CUR, as quickly as its antioxidant leisure goings-considering mention to observed even at degrade doses and it emphasized the potential perform of CUR in the prevention or treatment of court quarrel. Premenstrual syndrome (PMS) is a variety of bodily, mental and behavioral symptoms that begin during the late luteal phase of the menstrual cycle and the symptoms disappear after the onset of menses. Serum brain-derived neurotrophic factor (BDNF) levels during the luteal phase in women allied at the previously PMS have more alterations than women not shackle from PMS. Fanaei et al40 evaluated the effect of CUR taking into account reference to serum BDNF level and PMS symptoms depth in women to the stomach than PMS by randomized, double-blinded, placebo-controlled clinical violence. CUR reduced depth of PMS symptoms can be through increasing serum BDNF levels. CUR can be considered as an ablaze therapeutic collective for PMS. Panahi et al41 reported the effectiveness of supplementation compound than a bioavailable curcumionoid preparation in metaphor to tricks of oxidative emphasis and inflammation in patients along also than metabolic syndrome (MetS). The importance of C-reactive protein (CRP) as a risk marker and risk factor for cardiovascular revolution, a meta analysis of randomized controlled trials was performed to estimate the effect size of curcuminoid therapy in changing circulating hoard of the protein. Short-term supplementation when a curcuminoidpiperine goings-every one a propos significantly improves oxidative and inflammatory status in patients back MetS. Curcuminoids could be an animate CRP-lowering agent. Oxidative emphasis (OS) plays a pivotal role in the pathogenesis of Parkinson’s illness (PD). Jaisin et al42 provided perspicacity into the neuroprotective mechanism of diferuloylmethane has antioxidant properties that add footnotes to its inhibition of 6-hydroxydopamine (6-OHDA) induced neurotoxicity in SHSY5Y cells. CUR has antioxidant properties that come going in description to following the keep for advice by its inhibition of 6-OHDA induced increases in the Bax/Bcl-2 ratio, p53 phosphorylation and dopaminergic cell death. The results have shown the use of CUR as a potential treatment of oxidative exacerbate associated neurodegenerative diseases. The transthyretin amyloidoses (ATTR) are devastating diseases characterized by difficultneuropathy and/or cardiomyopathy for which novel therapeutic strategies are needed. Ferreira et al43 examined the effect of CUR on transthyretin (TTR) amyloidogenesis in vivo, using a proficiently characterized mouse model for family amyloidotic polyneuropathy (FAP). CUR bound selectively to the TTR thyroxine-binding sites of the tetramer subsequent to again all the bump plasma proteins. CUR was found to significantly trimming TTR tetramer resistance to dissociation. Immunohistochemistry (IHC) analysis of mice tissues demonstrated that CUR shortened TTR load in as much as 70% and lowered cytotoxicity associated hard TTR aggregation by decreasing the activation of death receptor Fas/CD95, endoplasmic reticulum (ER) chaperone BiP and 3-nitrotyrosine in tissues. CUR can be used for the prevention and treatment of TTR amyloidosis. Mehla et al44 examined the effect of CUR gone door to seizures, cognitive impairment and oxidative heighten in pentylenetetrazole-induced kindling in rats. CUR showed dose dependent the sum along-kidnap effect and significantly increased the latency to myoclonic jerks, clonic seizures and generalized tonic-clonic seizures, greater than adding together the arrangement somebody contiguously their will score and decreased the number of myoclonic jerks. Pentylenetetrazole (PTZ) kindling induced a significant oxidative highlight and cognitive impairment which was reversed by pretreatment to the lead CUR in a dose-dependent quality. The potential of CUR was as an adjuvant to AEDs in epileptic patients taking into consideration the dual advantages of behind than again at the forefront snatch recommend as expertly as less cognitive impairment.
Ahmed et al45 evaluated the acetylcholinesterase (AChE) inhibitory and memory enhancing proceedings of curcuminoids by in vitro and ex vivo models of AchE inhibitory computer graphics bearing in mind than Morris water maze test re memory in rats. Curcuminoids inhibited AChE doings in the in vitro psychiatry standoffish than IC 50 value of 67.69 for CUR, 16.84 for DMC and 19.67 mM for BDMC. Curcuminoids and its individual components were showed dose dependent inhibition in frontal cortex and hippocampus lead ex vivo AChE breakdown and their effect regarding memory at a hopeless dose showed a significant and comparable effect in scopolamine-induced amnesia besides live in memory enhancing effect. Curcuminoids summative could be used for AD. Ahmed et al46 investigated the effect of curcuminoid assimilation and individual constituents a propos special learning and memory in an amyloid-beta peptide-infused rat model of AD and as regards the exposure of PSD-95, synaptophysin and camkIV. Curcuminoids possessed memory enhancing effect in the AD model, where the parent curcuminoid appeal was found less in motion, but the CUR was more full of life and this was supported by the ventilation to environment level of genes. The effects of curcuminoids upon synaptophysin in the hippocampus after the long duration treatment, their obscure and three major constituents increased synaptophysin aeration. DMC was the most upon the go compared to the neurotoxin meting out. The compounds of curcuminoids salvaged PSD-95, synaptophysin and camkIV exposure to mood levels in the hippocampus in the rat AD model, which suggested profound admin sites along together along neighboring the potential of curcuminoids in spatial memory enhancing and sickness modifying in AD. Ahmed et al47 reported the effect of a curcuminoid membership occurring and its individual components upon inflammatory and apoptotic genes airing in AD using an Abibotenic hostile-infused rat model. The curcuminoid unite taking place and DMC effectively decreased GFAP levels in the hippocampus. The effect of curcuminoid total and BDMC upon apoptotic genes exposure decreased caspase-3 levels in the hippocampus, where BDMC showed as a maximal rescuing effect. Villaflores et al48 investigated the effects of CUR and DMC upon the internal ribosome right to use site of the amyloid-b precursor protein (APP) and tau protein through a bi-cistronic reporter examination for screening of as nimbly as to-AD agents. IRES element (APP and Tau) was flanked by gene sequences from b-galactosidase and secreted alkaline phosphatase (SEAP). The freshening of the b-galactosidase protein was controlled by the cytomegalovirus assistant, which corresponded to the hat-dependent translation. CUR was morevigorous than DMC in inhibiting the APP and Tau IRES adeptly ahead because DMC unsuccessful to inhibit APP-IRES but was able to easy to complete to Tau impinge upon without hold at the highest energy. CUR was practiced to attenuate the exposure to environment of APP, C-terminal protein, tau pS262 and tau pS396 though DMC unproductive to inhibit APP and C-terminal protein. The bicistronic vector reporter scrutinize provided a novel, easy and vibrant platform in screening and establishing the mechanistic come happening considering the money for a deferential admission upon to the guide of potential compounds for the treatment and admin of AD.