Cytoprotective Effects Of Curcumin Research Articles

Protective Effect of Curcuma Extract in an Ex Vivo Model of Retinal Degeneration via Antioxidant Activity and Targeting the SUMOylation.

Retinal degeneration is the major and principal cause behind many incurable blindness diseases. Several studies indicated the neuroprotective effect of Curcuma longa in eye pathologies, specifically retinopathy. However, the molecular mechanism behind its effect has not been completely elucidated. Using an ex vivo model of retinal degeneration obtained from an ex vivo optic nerve cut (ONC), we demonstrated that Curcuma extract (Cur) exerted a neuroprotective effect. Importantly, Cur was able to modulate apoptosis and MAPK signaling pathway activation and prevent retinal ganglion cell (RGC) loss. Other well-known neuroprotective pharmacological tools, including memantine (Mem), citicoline (Cit), and ginkgolic acid (GA), were used to compare the potential mechanisms of Cur. The antioxidant activity of retinas treated with Cur following optic nerve cut was significantly higher than control, but Cur failed to change the retina glutamate content. Considering the antioxidant effect of Cur and taking advantage of our recent findings on the crosstalk between oxidative stress and post-translational protein modifiers, in particular, small ubiquitin-related modifier (SUMO), we were interested in exploring the effect of Cur on SUMOylation. We found that Cur significantly prevented the increase of protein SUMOylation, confirming our previous in vitro data indicating the cytoprotective effect of curcumin through modulating the oxidative stress and SUMO-JNK axis. Altogether, these results suggest that Curcuma protects the retina from degeneration via antioxidant activity and targets SUMOylation. Therefore, it might be considered for the combination therapy with other neuroprotective agents with different mechanisms in preclinical studies on retinal degeneration.

Soluble curcumin ameliorates motility, adhesiveness and abrogate parthanatos in cadmium-exposed retinal pigment epithelial cells

Cadmium (Cd) is a nonessential transition metal and one of the most toxic environmental pollutants. Industrial, agricultural and urban activities are the main sources of Cd environmental contamination. Multiple deleterious effects of Cd exposure were reported for different cell types and living organisms in a great number of research papers. Cd bioaccumulation hazard is mediated by the relatively long half-life of this metal in an organism. For example, in mammals its half-life lasts for about 10–30 years. Cd exposure affects many tissues. However, some of them, including the central nervous system and sensory organs, are most susceptible to its toxicity. The harmful effects of Cd could be linked to oxidative stress generation and consequently intracellular signalling disruption. Since Cd induces redox imbalance the antioxidants could be a prospective tool to ameliorate Cd cytotoxicity. In present work, we have studied the protective efficacy of soluble curcumin on Cd-caused retinal pigment epithelium (RPE) cells viability, reactive oxygen species production, adhesive and extracellular matrix proteins expression, cell migration and parthanatos level. Low dose (5 µM) of soluble curcumin ameliorated all aforementioned indices of Cd-induced cytotoxicity. Curcumin has restored the RPE cells motility as well as fibronectin and E-cadherin expression. Therefore, the modulation of RPE adhesiveness could be regarded as a cytoprotective effect of curcumin. Furthermore, Cd-caused poly(ADP-ribose) polymerase-1 (PARP-1) suppression and cleaved PARP-1 upregulation were ameliorated by curcumin exposure. Therefore, the protective effect of soluble curcumin could be related, at least partially, to the modulation of PARP activity and inhibition of parthanatos flux. The observed results have demonstrated that low doses of soluble curcumin are a promising tool to protect RPE cells against Cd-caused retinal injury.

Curcumin protects against palmitic acid-induced apoptosis via the inhibition of endoplasmic reticulum stress in testicular Leydig cells

BackgroundPalmitic acid (PA) is a common saturated fatty acid that induces apoptosis in various types of cells, including testicular Leydig cells. There is evidence suggesting that PA is increased in patients with obesity and that PA-induced cell apoptosis may play an important role in obesity-related male infertility. Curcumin, a natural polyphenol, has been reported to exert cytoprotective effects in various cell types. However, the cytoprotective effect of curcumin against PA-induced apoptosis in Leydig cells remains unknown. Therefore, the current study was performed to investigate the protective effects of curcumin in response to PA-induced toxicity and apoptosis in murine Leydig tumor cell line 1 (MLTC-1) cells and explore the mechanism underlying its anti-apoptotic action.MethodsMLTC-1 cells were cultured in Roswell Park Institute-1640 medium and divided into five groups. First four groups were treated with 50–400 μM PA, 400 μM PA + 5–40 μM curcumin, 400 μM PA + 500 nM 4-phenylbutyric acid (4-PBA, an endoplasmic reticulum (ER) stress inhibitor), and 500 nM thapsigargin (TG, an ER stress inducer) + 20 μM curcumin, respectively, followed by incubation for 24 h. Effects of PA and/or curcumin on viability, apoptosis, and ER stress in MLTC-1 cells were then determined by cell proliferation assay, flow cytometry, and western blot analysis. The fifth group of MLTC-1 cells was exposed to 400 μM of PA and 5 IU/mL of human chorionic gonadotropin (hCG) for 24 h in the absence and presence of curcumin, followed by measurement of testosterone levels in cell-culture supernatants by enzyme-linked immunosorbent assay (ELISA). Rats fed a high-fat diet (HFD) were treated with or without curcumin for 4 weeks, and the testosterone levels were detected by ELISA.ResultsExposure to 100–400 μM PA reduced cell viability, activated caspase 3, and enhanced the expression levels of the apoptosis-related protein BCL-2-associated X protein (BAX) and ER stress markers glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in MLTC-1 cells. Treating cells with 500 nM 4-PBA significantly attenuated PA-induced cytotoxicity through inhibition of ER stress. Curcumin (20 μM) significantly suppressed PA- or TG-induced decrease in cell viability, caspase 3 activity, and the expression levels of BAX, CHOP, and GRP78. In addition, treating MLTC-1 cells with 20 μM curcumin effectively restored testosterone levels, which were reduced in response to PA exposure. Similarly, curcumin treatment ameliorated the HFD-induced decrease in serum testosterone level in vivo.ConclusionsThe present study suggests that PA induces apoptosis via ER stress and curcumin ameliorates PA-induced apoptosis by inhibiting ER stress in MLTC-1 cells. This study suggests the application of curcumin as a potential therapeutic agent for the treatment of obesity-related male infertility.

Investigation of the anti-cataractogenic mechanisms of curcumin through in vivo and in vitro studies

BackgroundCataract is the leading cause of blindness in elderly people worldwide, especially in developing countries. Studies to identify strategies that can prevent or retard cataract formation are urgently required. This study aimed to investigate the potential mechanism of the cytoprotective effects of curcumin in in vivo and in vitro experiments.MethodsMale Wistar rats were randomly divided into three groups: the control group, the model group (administered 20 μmol/kg sodium selenite), and the curcumin group (pretreated with 75 mg/kg body weight curcumin 24 h prior to the administration of sodium selenite). The expression levels of heat shock protein 70 (HSP70), the activities of 8-hydroxy-2-deoxyguanosine (8-OHdG), catalase (CAT), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were assessed by using RT-PCR assay and ELISA. In addition, the cell viability, cell apoptosis, and cell cycle were assessed using a CCK-8 assay and flow cytometry in in vitro studies, followed by RT-PCR analysis to identify the mRNA expression levels of caspase 3, Bcl-2 associated X (Bax), B-cell lymphoma 2 (Bcl-2), cyclooxygenase (Cox-2), c-met, and Slug.ResultsCataract was successfully established in rats of the model group and the curcumin group through intraperitoneal injection of sodium selenite. The expression levels of HSP70 and the activities of 8-OHdG and MDA in the curcumin group were decreased compared with those in the model group, whereas the activities of CAT, SOD, and GSH-Px were significantly higher than those in the model group (P < 0.05). In the in vitro studies, the cell viability and cell apoptosis significantly increased and decreased, respectively, in the curcumin group compared with the model group. Correspondingly, the mRNA expression of caspase-3, Bax, and Cox-2 was lower in the curcumin group than in the model group (P < 0.05).ConclusionsThis study suggested that curcumin attenuated selenite-induced cataract through the reduction of the intracellular production of reactive oxygen species and the protection of cells from oxidative damage.

Pretreatment of Adipose Derived Stem Cells with Curcumin Facilitates Myocardial Recovery via Antiapoptosis and Angiogenesis.

The poor survival rate of transplanted stem cells in ischemic myocardium has limited their therapeutic efficacy. Curcumin has potent antioxidant property. This study investigates whether prior curcumin treatment protects stem cells from oxidative stress injury and improves myocardial recovery following cells transplantation. Autologous Sprague-Dawley rat adipose derived mesenchymal stem cells (ADSCs) were pretreated with or without curcumin. The hydrogen peroxide/serum deprivation (H2O2/SD) medium was used to mimic the ischemic condition in vitro. Cytoprotective effects of curcumin on ADSCs were evaluated. Curcumin pretreatment significantly increased cell viability and VEGF secretion, and decreased cell injury and apoptosis via regulation of PTEN/Akt/p53 and HO-1 signal proteins expression. The therapeutic potential of ADSCs implantation was investigated in myocardial ischemia-reperfusion injury (IRI) model. Transplantation of curcumin pretreated ADSCs not only resulted in better heart function, higher cells retention, and smaller infarct size, but also decreased myocardial apoptosis, promoted neovascularization, and increased VEGF level in ischemic myocardium. Together, priming of ADSCs with curcumin improved tolerance to oxidative stress injury and resulted in enhancement of their therapeutic potential of ADSCs for myocardial repair. Curcumin pretreatment is a promising adjuvant strategy for stem cells transplantation in myocardial restoration.

Cytoprotective Effects of Curcumin on Sodium Fluoride-Induced Intoxication in Rat Erythrocytes

Curcumin is well known for its potent antioxidant activity. The result of numerous studies showed that antioxidants can protect against fluoride-induced toxicity. In the present study, protective effects of curcumin against sodium fluoride-induced toxicity in rat erythrocytes were evaluated. Curcumin (10 and 20 mg/kg) and vitamin C (10 mg/kg) were administrated intraperitoneally for 1 week followed by sodium fluoride (600 ppm) treatment for next week. Erythrocytes were isolated and superoxide dismutase and catalase activities as well as the levels of reduced glutathione, and lipid peroxidation were measured. The level of malondialdehyde in sodium fluoride treated rats (595.13 ± 20.23 nmol/g Hb) increased compared to the normal rats (315.44 ± 9.76 nmol/g Hb). Animals which were pretreated with curcumin at 20 mg/kg for 1 week prior to sodium fluoride intoxication showed significant reduction in the malondialdehyde level (320.22 ± 9.28 nmol/g Hb). Also, pretreated with curcumin (20 mg/kg) and vitamin C restored the superoxide dismutase and catalase activities and modified the level of reduced glutathione compared with control group (p > 0.01).

Curcumin protects PC12 cells against 1-methyl-4-phenylpyridinium ion-induced apoptosis by bcl-2-mitochondria-ROS-iNOS pathway

The aim of present study is to explore the cytoprotection of curcumin against 1-methyl-4-phenylpridinium ions (MPP(+))-induced apoptosis and the molecular mechanisms underlying in PC12 cells. Our findings indicated that MPP(+) significantly reduced the cell viability and induced apoptosis of PC12 cells. Curcumin protected PC12 cells against MPP(+)-induced cytotoxicity and apoptosis not only by inducing overexpression of Bcl-2, but also reducing the loss of mitochondrial membrane potential (MMP), an increase in intracellular reactive oxygen species (ROS) and overexpression of inducible nitric oxide synthase (iNOS). The selective iNOS inhibitor AG partly blocked MPP(+)-induced apoptosis of PC12 cells. The results of present study suggested that the cytoprotective effects of curcumin might be mediated, at least in part, by the Bcl-2-mitochondria-ROS-iNOS pathway. Because of its non-toxic property, curcumin could be further developed to treat the neurodegenerative diseases which are associated with oxidative stress, such as Parkinson's disease (PD).

Cytoprotective Effect of Curcumin in Human Proximal Tubule Epithelial Cells Exposed to Shiga Toxin

We conducted the following experiments to determine whether curcumin, an antioxidant compound extracted from the spice tumeric, inhibits cell death induced by Shiga toxin (Stx) 1 and 2 in HK-2 cells, a human proximal tubule cell line. Cells were incubated for 24–48 h with Stx1 or Stx2, 0–100 ng/ml. Test media contained either no further additives or 10–50 μM curcumin. Exposure to Stx1 and Stx2, 100 ng/ml, reduced cell viability to approximately 25% of control values after 24 h and 20 μM curcumin restored viability to nearly 75% of control. Cell staining confirmed that Stx1 and Stx2-induced damage in HK-2 cells involved a combination of apoptosis and necrosis. Thus, Stx1 caused apoptosis and necrosis in 12.2 ± 2.2 and 12.7 ± 0.9% of HK-2 cells, respectively. Similarly, Stx2 caused apoptosis and necrosis in 13.4 ± 2.1 and 9.0 ± 0.5% of HK-2 cells, respectively. Addition of 20 μM curcumin decreased the extent of apoptosis and necrosis to 2.9 ± 2.0 and 3.8 ± 0.2%, respectively in the presence of Stx1 and to 3.0 ± 2.1 and 3.9 ± 0.3%, respectively, for Stx2 (P < 0.01). Stx-induced apoptosis and its inhibition by curcumin were confirmed by DNA gel electrophoresis and by an assay for fragmentation. The protective effect of curcumin against Stx1 and Stx2-induced injury to HK-2 was not related to its antioxidant properties. Instead, curcumin enhanced expression of heat shock protein 70 (HSP70) in HK-2 cells under control conditions and after exposure to Stx1 or Stx2. No injury was detectable after incubation of LLC-PK1 or OK cells, non-human proximal tubule cell lines, with Stx1 or Stx2. Thus, curcumin inhibits Stx-induced apoptosis and necrosis in HK-2 cells in vitro. The cytoprotective effect of curcumin against Stx-induced injury in cultured human proximal tubule epithelial cells may be a consequence of increased expression of HSP70.

Cytotoxic and cytoprotective activities of curcumin: Effects on paracetamol-induced cytotoxicity, lipid peroxidation and glutathione depletion in rat hepatocytes

The cytoprotective effect of curcumin, a natural constituent of Curcuma longa, on the cytotoxicity of paracetamol in rat hepatocytes was studied. Paracetamol was selected as a model-toxin, since it is known to be bioactivated by 3-methylcholanthrene inducible cytochromes P450 presumably to N-acetyl- p-benzoquinone imine (NAPQI), a reactive metabolite which upon overdosage causes protein- and non-protein thiol-depletion, lipid peroxidation and cytotoxicity measured as LDH-leakage. At low concentrations curcumin was found to protect significantly against paracetamol-induced lipid peroxidation, without protection against paracetamol-induced LDH-leakage and without protection against paracetamol-induced GSH-depletion. At a 100 times higher concentration of curcumin the observed protective effect on lipid peroxidation was accompanied with a tendency to increase cellular GSH-depletion and LDH-leakage. No time-dependency was found as to the curcumin-induced effects: treatment of the hepatocytes 1 hr before, concomitantly or 1 hr after the addition of paracetamol to the cells had similar effects. In contrast to what was expected on the basis of previous in vivo experiments, at higher concentrations curcumin itself was found to be slightly cytotoxic. Curcumin-induced LDH-leakage was accompanied by a significant depletion of GSH. It has been concluded that the observed cytoprotective and cytotoxic activities of curcumin may be explained by a strong anti-oxidant capacity of curcumin and the capability of curcumin to conjugate with GSH. Furthermore, it has been concluded that lipid peroxidation is not playing a causal role in cell-death induced by paracetamol or by curcumin.