Protective Effect Of Curcumin Research Articles

Curcumin ameliorates oxidative stress-induced intestinal barrier injury and mitochondrial damage by promoting Parkin dependent mitophagy through AMPK-TFEB signal pathway

The gut epithelial is known as the most critical barrier for protection against harmful antigens and pathogens. Oxidative stress has been implicated in the dysfunction of the intestine barrier. Hence, effective and safe therapeutic approaches for maintaining intestinal redox balance are urgently needed. Curcumin has gained attention for its vast beneficial biological function via antioxidative stress. However, whether the curcumin can relief intestine damage and mitochondrial injury induced by oxidative stress is still unclear. In this study, we found that curcumin can effectively ameliorate hydrogen peroxide (H2O2)-induced oxidative stress, intestinal epithelial barrier injury and mitochondrial damage in porcine intestinal epithelial cells (IPEC-J2 cells) in a PTEN-induced putative kinase (PINK1)-Parkin mitophagy dependent way. Mechanistically, depletion of Parkin (a mitophagy related protein) abolished curcumin's protective action on anti-oxidative stress, improving intestinal barrier and mitochondrial function in porcine intestinal epithelial cells (IPEC-J2) induced by H2O2. Consistently, the protective effect of curcumin was not found in cells transfected with GFP-ParkinΔUBL, which encodes a mutant Parkin protein without the ubiquitin E3 ligase activity, indicating that the ubiquitin E3 ligase of Parkin is required for curcumin's protective effects. On the other hand, we also found that the protective function of curcumin was diminished when PRKAA1 was depleted in IPEC-J2 cells treated with H2O2. Immunofluorescence and luciferase assay showed that curcumin dramatically enhanced nuclear translocation and transcriptional activity of transcription factor EB (TFEB) in IPEC-J2 cells treated with H2O2, and it was ameliorated by co-treated with compound C, an Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor, which means curcumin promotes TFEB transcript via AMPK signal pathway. Consistent with in vitro data, dietary curcumin protected intestinal barrier function, improved redox status, alleviated mitochondrial damage, triggered mitophagy and influenced AMPK-TFEB signal pathway in a well-established pig oxidative stress model by challenging with diquat. Taken together, these results unveil that curcumin ameliorates oxidative stress, enhances intestinal barrier function and mitochondrial function via the induction of Parkin dependent mitophagy through AMPK activation and subsequent TFEB nuclear translocation.

Curcumin: Novel Treatment in Neonatal Hypoxic-Ischemic Brain Injury.

Hypoxic-ischemic encephalopathy (HIE) is a major cause of mortality and morbidity in neonates, with an estimated global incidence of 3/1,000 live births. HIE brain damage is associated with an inflammatory response and oxidative stress, resulting in the activation of cell death pathways. At present, therapeutic hypothermia is the only clinically approved treatment available for HIE. This approach, however, is only partially effective. Therefore, there is an unmet clinical need for the development of novel therapeutic interventions for the treatment of HIE. Curcumin is an antioxidant reactive oxygen species scavenger, with reported anti-tumor and anti-inflammatory activity. Curcumin has been shown to attenuate mitochondrial dysfunction, stabilize the cell membrane, stimulate proliferation, and reduce injury severity in adult models of spinal cord injury, cancer, and cardiovascular disease. The role of curcumin in neonatal HIE has not been widely studied due to its low bioavailability and limited aqueous solubility. The aim of this study was to investigate the effect of curcumin treatment in neonatal HIE, including time of administration and dose-dependent effects. Our results indicate that curcumin administration prior to HIE in neonatal mice elevated cell and tissue loss, as well as glial activation compared to HI alone. However, immediate post-treatment with curcumin was significantly neuroprotective, reducing grey and white matter tissue loss, TUNEL+ cell death, microglia activation, reactive astrogliosis, and iNOS oxidative stress when compared to vehicle-treated littermates. This effect was dose-dependent, with 200 μg/g body weight as the optimal dose-regimen, and was maintained when curcumin treatment was delayed by 60 or 120 min post-HI. Cell proliferation measurements showed no changes between curcumin and HI alone, suggesting that the protective effects of curcumin on the neonatal brain following HI are most likely due to curcumin’s anti-inflammatory and antioxidant properties, as seen in the reduced glial and iNOS activity. In conclusion, this study suggests curcumin as a potent neuroprotective agent with potential for the treatment of HIE. The delayed application of curcumin further increases its clinical relevance.

Protective effect of curcumin on fertility in cyclophosphamide exposed rats: Involvement of multiple pathways.

This study assesses the effect of curcumin on cyclophosphamide (CPA)-induced functional alterations of the testicular, brain, and pituitary axis in common rodents, rats. Only CPA was given at 150mg/kg body weight only on Day 1 or orally pre and posttreated with curcumin at 20mg/kg body weight successively for 14days. The outcomes showed that curcumin pre and posttreatments significantly affected the elevation of biomarkers of oxidative stress in CPA-induced rats, moreover, it increased nonenzymatic antioxidant levels in the epididymis, testes, and brain of the treated rats used in this study. In addition, followed by the preservation of histo-architectures of the epididymis, testes, and brain in the rats treated with CPA, curcumin helped in increasing the sperm quality and quantity and suppressing both the inflammatory indices and the activities of caspase-3, while pretreatment with curcumin gave a better result than posttreatment with curcumin. This may, therefore, represent a prospective adjuvant against CPA-induced spermatogenic deficits in humans. PRACTICAL APPLICATIONS: Jointly, through the antiapoptotic, antioxidant, and anti-inflammatory activities of curcumin, it instigated the toxicity of CPA-induced to be modulated along the testicular, brain, and pituitary axis in the rats. This may, therefore, represent a prospective therapeutic adjuvant against CPA-induced spermatogenic deficits in humans.

Protective effects of curcumin against chronic alcohol-induced liver injury in mice through modulating mitochondrial dysfunction and inhibiting endoplasmic reticulum stress.

BackgroundCurcumin is a major active ingredient extracted from powdered dry rhizome of Curcuma longa. In Ayurveda and traditional Chinese medicine, it has been used as a hepatoprotective agent for centuries. However, the underlying mechanisms are not clear.ObjectiveThe present study is to investigate the hepatoprotective effects of curcumin in chronic alcohol-induced liver injury and explore its mechanism.DesignAlcohol-exposed Balb/c mice were treated with curcumin (75 and 150 mg/kg) once per day for 8 weeks. Tissue from individual was fixed with formaldehyde for pathological examination. The activities of mitochondrial antioxidant enzymes, Na+/k+-ATPase, Ca2+-ATPase, and Ca2+Mg2+-ATPase, were determined. The level of mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPTP) opening was also determined. The expression of PGC-1α, NRF1, Mn-SOD, GRP78, PERK, IRE1α, nuclear NF-κB, and phosphorylated IκBα was quantified by western blot. The contents of TNF-α, IL-1β, and IL-6 in the liver were measured using the ELISA method.ResultsCurcumin significantly promoted hepatic mitochondrial function by reducing the opening of MPTP, thus increasing the MMP, promoting the activity of Na+/k+-ATPase, Ca2+-ATPase, and Ca2+/Mg2+-ATPase, and attenuating oxidative stress. Curcumin upregulated the expression of PGC-1α, NRF1, and Mn-SOD, and downregulated the expression of GRP78, PERK, and IRE1α in hepatic tissue. Curcumin also attenuated inflammation by inhibiting the IκBα–NF-κB pathway, which reduced the production of TNF, IL-1β, and IL-6.ConclusionCurcumin attenuates alcohol-induced liver injury via improving mitochondrial function and attenuating endoplasmic reticulum stress and inflammation. This study provides strong evidence for the beneficial effects of curcumin in the treatment of chronic alcohol-induced liver injury.

Homocysteine-Induced Damage of Cultured Glioblastoma Cells: Amelioration by Curcumin

High levels of homocysteine (Hcy) were shown to be a significant independent risk factor for some neurological diseases. Such a condition induces excessive production of reactive oxygen species (ROSs) in human glioma cells. Curcumin, an active component of turmeric (Curcuma longa), provides strong antioxidant effects in in vitro and in vivo experimental models. However, mechanisms of the effect of curcumin against Hcy-induced cell damage have not yet been elucidated in detail. This study investigated whether curcumin can protect cultured U373 glioblastoma cells against Hcy-induced damage, and what are probable cellular mechanisms of this effect, namely, alterations in the expressions of a transcription factor (nuclear E2-related factor-2, Nrf2), hemoxygenase 1 (HO-1), and TP53-induced glycolysis and apoptosis regulator (TIGAR). The results showed that curcumin partially enhanced cell viability of Hcy-treated cells and significantly attenuated intracellular ROS formation. Pretreatment of curcumin also partially moderated Hcy-induced oxidative damage via HO-1 expression through activating Nrf2 expression. Furthermore, TIGAR also contributed to the protective effect of curcumin against cell damage caused by Hcy in the U373 cell line. Taken together, these results indicate that modulation of the Nrf2/HO-1 signal pathway and TIGAR expression can play a pivotal role in the protective effects of curcumin against Hcy-induced oxidative damage in glial cells.

Effect of Nanomicelle Curcumin on Quality of Life and Sleep in Patients With Parkinson’s Disease: A Double-Blind, Randomized, and PlaceboControlled Trial

Background: Considering the evidence indicating the neuronal protective effects of curcumin in previous studies, this double-blind, randomized, placebo-controlled, and parallel-group trial was aimed at exploring the possible nanomicelle curcumin (SinaCurcumin®, nano-micellar soft gel)- mediated impact on sleep, fatigue, and quality of life (QoL) in patients with Parkinson’s disease (PD). Methods: A sample of 50 PD patients were recruited and randomly divided into experimental (25) and control groups (25). Sleep quality, fatigue, and QoL were assessed based on the Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), and the Parkinson’s Disease Questionnaire–39 (PDQ-39), respectively, at the beginning and the end of the study. The groups were treated for three months by 80 mg of nano-micellar soft gel twice a day. Results: Nanomicelle curcumin significantly increased sleep quality and QoL compared with placebo (P values=0.0001 and 0.0002, respectively) in PD patients. This significant difference has not influenced by the duration of the disease, the severity of disease progression (Hoehn & Yahr scale), and the cumulative dose of levodopa. This supplement did not have a significant effect on the fatigue severity of patients compared to placebo. Conclusion: It has proposed that the nanomicelle curcumin can be used to improve sleep quality and QoL in PD patients.

The protective effects of curcumin on cytotoxic and teratogenic activity of retinoic acid in mouse embryonic liver.

Retinoic acid (RA) is a synthetic vitamin derivative. It exerts toxic and teratogenic effects on the development of embryonic organs in dose- and time-dependent manners in mice. Curcumin is a compound obtained from rhizomes of turmeric (Curcuma longa) and has protective effects on teratogenic agents. The current study examined the effects of curcumin on embryos treated with RA. A total of 24 female NMRI mice (8-week-old pregnant mice) were investigated in the current study. All of them were treated for 10 days during days 15 to 50 of pregnancy. In the first group, the animals were fed with normal diets (control); in the second group, with 60 mg/kg all- trans RA; in the third group, with 10 mg/kg curcumin; and in the fourth group, with RA and curcumin in their diets. The animals were killed by cervical dislocation at the 18th day of pregnancy and embryos were separated from the uteruses. The embryo weight and crown rump (CR) length were measured, and the SPSS software was used to analyze data. There was a significant increase in the lengths of CR and weights of embryos after using curcumin, but RA had no effect on the length of CR and weight of embryos at a dose of 60 mg/kg. Morphometric assay of liver tissue was performed, and data analysis indicated that there were significant differences between groups in terms of morphometric parameters of liver tissue. Therefore, RA increased the cell number and sinusoid diameter and decreased the cell areas in the embryonic liver tissue. However, curcumin decreased these side effects of RA on the embryonic liver tissue. The results indicated that curcumin could decrease the toxic and teratogenic effects of RA in mouse embryos.

Role of Autophagy on Heavy Metal-Induced Renal Damage and the Protective Effects of Curcumin in Autophagy and Kidney Preservation.

Curcumin is a hydrophobic polyphenol compound extracted from the rhizome of turmeric. The protective effect of curcumin on kidney damage in multiple experimental models has been widely described. Its protective effect is mainly associated with its antioxidant and anti-inflammatory properties, as well as with mitochondrial function maintenance. On the other hand, occupational or environmental exposure to heavy metals is a serious public health problem. For a long time, heavy metals-induced nephrotoxicity was mainly associated with reactive oxygen species overproduction and loss of endogenous antioxidant activity. However, recent studies have shown that in addition to oxidative stress, heavy metals also suppress the autophagy flux, enhancing cell damage. Thus, natural compounds with the ability to modulate and restore autophagy flux represent a promising new therapeutic strategy. Furthermore, it has been reported in other renal damage models that curcumin’s nephroprotective effects are related to its ability to regulate autophagic flow. The data indicate that curcumin modulates autophagy by classic signaling pathways (suppression of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and/or by stimulation of adenosine monophosphate-activated protein kinase (AMPK) and extracellular signal-dependent kinase (ERK) pathways). Moreover, it allows lysosomal function preservation, which is crucial for the later stage of autophagy. However, future studies of autophagy modulation by curcumin in heavy metals-induced autophagy flux impairment are still needed.

Protective effects of curcumin and silymarin against paracetamol induced hepatotoxicity in adult male albino rats

BackgroundAcute paracetamol (PCM) toxicity is a clinical problem; can result in a serious liver injury that finally may progress to acute liver failure. Curcumin (CUR) is a prevalent natural compound that can maintain prooxidant/antioxidant balance and thus can help in liver protection; also, Silymarin (SL) is a traditional antioxidant herb, used to treat liver disorders through scavenging free radicals. This study aimed to illustrate the histological, biochemical and molecular changes induced by acute PCM overdose on rats' liver to elucidate the effectiveness of CUR compared to SL in alleviating such changes. Materials and methodsMale Wister Albino rats were divided into 6 groups each comprising 23 rats: control group, curcumin (CUR) treated group received (100 mg CUR/ kg), silymarin treated group received (100 mg SL/kg) for 7 successive days. Paracetamol (PCM) exposed group administered a single dose of PCM (200 mg/kg orally on 8th day). PCM + CUR group and PCM + SL group pretreated with CUR and SL respectively for 7 days then received single PCM dose (200 mg/kg) on the 8th day. Blood and liver tissues were collected for biochemical, histopathological and immunohistochemical analyses using anti-p53 antibody. In addition, real time polymerase chain reaction (RT- PCR) was used to measure Bax, bcl2 and Peroxisome proliferator-activated receptor-gamma (PPAR γ) mRNA expression levels. ResultsIn the paracetamol overdose group, the liver architecture showed necrotic changes, hydropic degeneration, congestion and dilatation of central veins. This hepatocellular damage was confirmed by a significant increase of AST, ALT levels and by an apparent increase in the number of p53 stained cells. PCM toxicity showed significant elevation of total oxidant status (TOS), oxidant status index (OSI) and decreased total antioxidant capacity (TAC) compared to controls (p < 0.001). Gene expression analysis showed that PCM caused an elevation of bcl2 and a reduction of both Bax and PPARγ mRNA expression. The histological alternation in the liver architecture was markedly improved in (PCM + CUR) group compared to (PCM+ SL) group, with an obvious decrease in the number of P53 stained cells. CUR pretreatment inhibited the elevation of TOS and OSI as well as the reduction of TAC caused by PCM toxicity compared to (PCM + SL) group. ConclusionBoth SL and CUR pretreatment prevented the toxic effects of PCM, but CUR is more effective than SL in ameliorating acute PCM induced hepatotoxicity.

The protective effect of curcumin on the lipid peroxidation caused by lead poisoning in rat

Objective To evaluate the effect of curcumin on the lead burden in lead-exposed rats, and to study whether curcumin can influence the lipid peroxidation caused by lead exposure. Methods A total of 70 rats of 21-day-old rats were divided randomly to 7 groups, the control group was given normal diet and drinking water, the curcumin group was given curcumin only 1 month after normal drinking water being given; the other 5 lead-exposed groups were given 2 g/L of acetate lead in free drinking water for 1 month and then randomly divided into lead-exposed group, low, medium and high concentration curcumin groups and Dimercaptosuccinic acid(DMSA) group, relatively.Lead levels of lead-exposed rats were determined by using inductively coupled plasma mass spectrometry, and commercial kit was used to detect antioxidant enzymes, and glutathione related enzymes and lipid peroxides. Results The lead concentrations in the blood, hippocampus, liver and kidney of lead-exposed group increased, the levels of each group were (221.76±12.59) μg/L, (1.10±0.11) μg/g, (1.40±0.12) μg/g, (8.26±0.47) μg/g, and (57.58±6.09) μg/g, respectively; compared with the lead-exposed group, the lead concentrations reduced in the blood, hippocampus, liver and kidney significantly (F=90.67, 39.07, 27.34, 86.04, all P=0.000) in the curcumin-treated group, while the effect of curcumin in the bones showed no significant difference between groups(F=5.65, P=0.230). Lead could significantly improve the level of lipid peroxides in the serum and hippocampus, and curcumin-treated groups could significantly reduce the level of lipid peroxidation(F=58.03, 19.25, 32.27, 24.83, all P=0.000) and (F=28.18, 33.71, 38.95, 32.11, all P=0.000); lead could also reduce the antioxidant enzyme activity in the serum and hippocampus; curcumin-treated groups could significantly increase the antioxidant enzyme activity (F=18.24, 78.65, all P=0.000) and (F=13.68, 17.04, all P=0.000), respectively.The concentration in the curcumin group was better than that of DMSA group (P<0.05). Conclusions Curcumin can downregulate the lead concentrations in the blood, hippocampus, liver and kidney and improve the activity of antioxidant enzymes, inhibit the oxidative stress induced by lead, and thus resist the lead-induced damage. Key words: Lead; Curcumin; Neurologic damage; Reactive oxygen species

Curcumin attenuates hypoxia/reoxygenation‑induced cardiomyocyte injury by downregulating Notch signaling.

Recovery of the blood supply is the most effective treatment against ischemic heart disease; however, it is also a major cause of myocardial ischemia/reperfusion injury in clinical therapy. Curcumin has been reported to possess beneficial effects against hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury by regulating cell proliferation, apoptosis and antioxidant enzyme activity. The aim of the present study was to investigate the molecular mechanisms underlying the effects of curcumin on H/R-injured cardiomyocytes. H9C2 cardiomyocytes were pretreated with curcumin, and then cultured under H/R conditions. The viability of H9C2 cells was measured using a Cell Counting kit-8 assay, and the levels of intracellular lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to assess cell injury. Levels of reactive oxygen species (ROS) and apoptosis were evaluated by flow cytometry. The expression levels of Notch intracellular domain (NICD) and numerous downstream genes were analyzed via reverse transcription-quantitative polymerase chain reaction and western blotting. The results revealed that curcumin protected H9C2 cells against H/R-induced injury, reversing the H/R-induced increases in LDH and MDA levels, and decreases in SOD levels. ROS levels in H/R-induced cells were also significantly downregulated by curcumin treatment (P<0.01), and the apoptotic rate was significantly decreased from 15.13% in the H/R group to 7.7% in the H/R + curcumin group (P<0.01). The expression levels of NICD, hairy and enhancer of split (Hes)-1, Hes-5 and hairy/enhancer-of-split related with YRPW motif protein 1 (Hey-1) were significantly decreased in H/R-treated cells following curcumin treatment. Treatment with Jagged1 attenuated the effects of curcumin on cell viability, ROS levels and apoptosis; the Notch pathway was also reactivated. The present study indicated that there was a role for the Notch pathway in the protective effects of curcumin against H/R-induced cardiomyocyte injury, suggesting that downregulation of the Notch pathway may alleviate H/R-induced injury in H9C2 cells.

Protective Effects of Curcumin in High Fat Diet (HFD)-Induced Obesity Include Anti-Inflammatory Effects in Adipose Tissue and Changes in Gut Microbiome (P06-075-19)

ObjectivesCurcumin, a traditionally used spice in Asia has several health-protecting effects. However, its role on gut microbiota and obesity-associated inflammation is still poorly understood. The objective of this study was to determine whether the protective effects of curcumin in high fat diet (HFD)-induced obesity are mediated by reduced white adipose tissue (WAT) inflammation and changes in gut bacteria. MethodsMale B6 mice were fed a HFD (45% kcal fat) or HFD supplemented with 0.4% (w/w) curcumin (HFC) for thirteen weeks. Body weight, adiposity, glucose and, insulin tolerances, and serum triglycerides, insulin, leptin, resistin levels were measured. Gut microbiome composition was determined by 16S RNA metagenomics sequencing. Expression of inflammation-related genes in WAT was measured by qRT-PCR. Macrophage contents in WAT were evaluated by galectin-3 immunohistochemical staining. ResultsPro-inflammatory transcription factor nuclear factor NF-kappa-B p65 subunit (p65) and toll-like receptor-4 (TLR-4) gene expression was downregulated in HFC group compared to HFD mice. Furthermore, curcumin reduced total macrophage infiltration in WAT in HFC mice compared to HFD group. Expression of both M1 (CD80, CD38) and M2 (Arginase-1) associated genes was decreased. The relative abundance of bacteria representing the Clostridium genus, which contains numerous short-chain fatty acid (SCFA) producing species, was increased by the curcumin supplement. ConclusionsCurcumin exerts protective effects in dietary obesity, in part through downregulation of adipose tissue inflammation which may be due to the production of SCFA and, possibly other curcumin metabolites by gut microflora. Funding SourcesStartup funds and Come N Go award from the College of Human Sciences at Texas Tech University.

The protective effect of curcumin against aluminum chloride-induced oxidative stress and hepatotoxicity in rats

Aluminum is recognized as a public health concern because of its potential toxic effects on human health. Therefore, the present experiment was undertaken to determine the effectiveness of curcumin (CUR) in reducing the hepatotoxicity induced by aluminum chloride (AlCl3) in animals. In this experimental study, forty male rats were allocated to five groups (N = 8), viz. no treatment (control), solvent (DMSO or distilled water), CUR (10 mg/kg B.W.), AlCl3 (10 mg/kg B.W.), and CUR+AlCl3 (each with 10 mg/kg B.W.). Treatments were performed by intra-peritoneal injections for 28 days. On the final day, animals were sacrificed, and liver function markers in blood plasma, hepatic antioxidants, and lipid peroxidation index in liver homogenate were estimated. AlCl3 treatment resulted in a significant increase in plasma AST, ALT, ALP and LDH activities with decreased total protein compared to control. AlCl3 significantly reduced superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels but increased malondialdehyde (MDA) level in the liver compared to control. AlCl3 also caused various histopathological changes in the livers of rats. Curcumin could normalize nearly all these parameters. CUR improved levels of changes in different parameters when was combined with AlCl3. It is concluded that CUR has beneficial effects being able to antagonize AlCl3 toxicity.

Protective effects of curcumin on biochemical and molecular changes in sodium arsenite-induced oxidative damage in embryonic fibroblast cells.

The present study was aimed atdeterminingthe oxidative damage caused by sodium arsenite in 3T3 fibroblast cells and the possible protective role of curcumin (Cur) against sodium arsenite toxicity. Embryonic fibroblast cells were exposed to sodium arsenite (0.01, 0.1, 1, and 10 μM) in the presence and absence of Cur (2.5 μM) for 24 hours. Cell viability, cytotoxicity, lipid peroxidation, hydroxyl radical, hydrogen peroxide, antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase) and expression levels of antioxidant genes (superoxide dismutase, catalase, and glutathione peroxidase) were measured in embryonic fibroblast cells. Results demonstrated that sodium arsenite directly affects antioxidant enzymes and genes in 3T3 embryonic fibroblast cells and induces oxidative damage by increasing the amount of hydrogen peroxide, hydroxyl radical, and lipid peroxidation in the cell. Furthermore, the study indicated that Cur might be a potential ameliorative antioxidant to protect the fibroblast cell toxicity induced by sodium arsenite.

Assessment of epigenetic changes and oxidative DNA damage in rat pups exposed to polychlorinated biphenyls and the protective effect of curcumin in the prenatal period.

Background Polychlorinated biphenyls (PCBs) are persistent organic chemicals that exert neurotoxic and endocrine disrupting effects. The aims of this study were to examine the effects of prenatal Aroclor 1254 (PCBs mixture) exposure on central nervous system tissues DNA and to evaluate the effects of curcumin. Methods Rat pups were assigned to three groups: [Group 1], Aroclor 1254 administrated group; [Group 2], Aroclor 1254 and curcumin administrated group; and [Group 3], control group. Plasma, cerebrum, cerebellum, pons and medulla oblongata tissue homogenates 8-hydroxy-2'-deoxyguanosine [8-(OH)DG] levels and plasma freeT4 levels were determined. Global DNA methylation and hydroxymethylation status were determined in cerebrum, cerebellum, pons and medulla oblongata. To this aim, DNA 5-hydroxymethylcytosine and 5-methylcytosine levels were measured, respectively. Results Mean cerebellum and cerebral cortex 5-hydroxymethylcytosine and 5-methylcytosine levels were higher in the control group than in the experimental groups. Mean plasma, cerebellum and cerebral cortex 8-(OH)DG concentrations were higher in Group 1 than the control group. No statistically significant difference was observed between Group 2 and the control group in terms of cerebellum and cerebral cortex 8-(OH)DG concentrations. Histopathological changes were also observed in the cerebral cortex and cerebellum of rat pups exposed to Aroclor 1254. PCBs exposure changes both DNA methylation and hypomethylation status and induces cerebellar and cerebral cortex DNA damage in the prenatal period. Exogenous curcumin may have protective effect on PCBs-induced DNA damage in cerebellum and cerebral cortex.

Protective effects of curcumin on radioiodine-induced salivary gland dysfunction in mice.

Radioiodine (RI) treatment is widely used in patients with differentiated thyroid cancer. However, RI exposure often induces salivary gland (SG) dysfunction. In this study, we investigated the effect of curcumin on RI-induced SG dysfunction in mice. Mice were assigned to one of four groups (n=6 per group) as follows: normal control, RI only, RI+curcumin, and RI+amifostine group. Salivary flow rate, lag time, and changes in 99m Tc (technetium)-pertechnetate uptake and excretion were measured, and changes in SG morphology and histology were analysed. Salivary epidermal growth factor content, amylase, and superoxide dismutase (SOD) activities were also measured. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was performed to assess SG apoptosis, and the expression of apoptosis-related protein was determined by western blotting. The reduced salivary flow rate and prolonged lag time in the RI group was restored by treatment with curcumin or amifostine. In the histological analysis, compared with the RI group, RI+curcumin and RI+amifostine groups had more mucin-rich acini and less periductal fibrosis. Compared with the RI group, RI+curcumin and RI+amifostine groups showed evidence of tissue remodelling, with a greater number of salivary epithelial cells (AQP-5-positive), SG ductal cells (CK18-positive), endothelial cells (CD31-positive), and myoepithelial cells (α-SMA-positive). RI+curcumin and RI+amifostine groups alleviated RI-induced cell death, demonstrating antiapoptotic effect, compared with the RI group. Both SOD activity and the protein expression levels of SOD2 were higher in the RI+curcumin and RI+amifostine groups than in the RI group. Our results demonstrate that curcumin ameliorates RI-induced SG dysfunction in mice.

The impact of curcumin and its modified formulations on Alzheimer's disease.

Alzheimer's disease (AD) is a major health problem worldwide, with no effective treatment approach. Curcumin is the main ingredient of turmeric traditionally used in Asian medicine. Several experimental studies have indicated the protective effect of curcumin and its novel formulations in AD. Curcumin has antioxidant, anti-inflammatory and neurotrophic activities, proposing a strong potential to prevent neurodegenerative diseases. However, there are no sufficient clinical trials to confirm curcumin use in AD patients. Low bioavailability following oral administration of curcumin limits its usage in human. The present study was designed to gather the effects of curcumin and its modified formulations in human and experimental models of AD.

Protective effects of curcumin against rotenone-induced neurotoxicity

Protective effects of curcumin against rotenone-induced neurotoxicity

Protective effect of curcumin against irinotecan‑induced intestinal mucosal injury via attenuation of NF‑κB activation, oxidative stress and endoplasmic reticulum stress.

Irinotecan (CPT‑11) is a DNA topoisomeraseI inhibitor which is widely used in clinical chemotherapy, particularly for colorectal cancer treatment. However, late‑onset diarrhea is one of the severe side‑effects of this drug and this restricts its clinical application. The present study aimed to investigate the protective effects of curcumin treatment on CPT‑11‑induced intestinal mucosal injury both invitro and invivo and to elucidate the related mechanisms involved in these effects. For this purpose, mice were intraperitoneally injected with CPT‑11 (75mg/kg) for 4days to establish a model of late‑onset diarrhea. Curcumin (100mg/kg) was intragastrically administered 8days before the injection of CPT‑11. Injury to small intestinal tissues was examined by H&E staining. The protein expression of prolyl4‑hydroxylase subunit beta (P4HB) and peroxiredoxin4(PRDX4) was detected by immunohistochemistry, as well as western blot analysis. IEC‑6 cell viability was detected by MTT assay. Flow cytometry was performed to examine the cell apoptotic rate, mitochondrial membrane potential and reactive oxygen species(ROS) generation. Immunofluorescence was used to observe the localization of nuclear factor (NF)‑κB. The levels of cleaved caspase‑3, glucose‑regulated protein, 78kDa (GRP78), P4HB, PRDX4 and CHOP were detected by western blot analysis. The results revealed that invivo, curcumin effectively attenuated the symptoms of diarrhea and abnormal intestinal mucosa structure induced by CPT‑11 in nude mice. Treatment with curcumin also increased the expression of P4HB and PRDX4 in the tissue of the small intestine. Invitro, curcumin, exhibited little cytotoxicity when used at concentrations <2.5µg/ml for 24h in IEC‑6 cells. At this concentration, curcumin also improved cell morphology, inhibited apoptosis, maintained mitochondrial membrane potential and reduced the elevated levels of ROS induced by CPT‑11 (20µg/ml). Furthermore, curcumin abolished NF‑κB signal transduction and protected the cells from CPT‑11‑induced apoptosis by upregulating the expression of molecular chaperones, such as GRP78, P4HB and PRDX4, and suppressing the levels of the apoptosis‑related proteins, CHOP and cleaved caspase‑3. On the whole, our data indicate that curcumin exerted protective effects against CPT‑11‑induced intestinal mucosa injury. The protective effects of curcumin are mediated by inhibiting the activation of NF‑κB, and suppressing oxidative stress and endoplasmic reticulum stress.

Protective effects of curcumin on ischemic reperfusion of rat retina

Ischemic reperfusion is an optic neuropathy in which photoreceptor cells may die through an apoptotic process. Free radicals are involved in the apoptotic process of ischemic reperfusion disorders. Previous research indicates that curcumin is an antioxidant found in plants which reduces neurodegenerative changes in aged animals. The purpose of this research was to survey whether curcumin has preventive effects on ischemic reperfusion of the retina. Twenty male Wistar rats were grouped into four (n = 5): 1, control group; 2, ischemic reperfusion group; 3, experimental group II: received 0.01% curcumin in diet (low dose) for 2 days before ischemic reperfusion; 4, experimental group III: received 0.25% curcumin in diet (high dose) for 2 days before ischemic reperfusion. The eye was enucleated and the retina separated. Routine tissue processing in transmission electron microscopy was done. Results showed that ischemic reperfusion created major signs of injury in the photoreceptor layer such as disappearance of the outer segment, cell swelling, and karyolitic and pyknotic nuclei, but cell swelling and karyolitic nuclei were not seen after receiving a low dose of curcumin. Also, the photoreceptor layer appeared normal after receiving a high dose of curcumin, but decreased vacuolization and dark and inactive nuclei were obvious. This study concluded that a high dose of curcumin confers a more preventive effect on retinal injury by ischemic reperfusion than a low dose.