• YAKHAK HOEJI
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• v.44 no.5
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• pp.448-454
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• 2000

Microglia, brain resident macrophages, play a central role in the inflammatory responses of the brain and are activated in brain injuries and several neurodegenerative diseases such as Alzheimer's and Parkinson's disease, thereby aggravating the course of these diseases. In this study, the effects of plantderived compounds such as curcumin or gingerol on the microglial activation were examined. Microglial cultures were prepared from 2~3 week mixed primary glial cultures obtained from the cerebral cortex of 1~2 day old rats and identified by immunocytochemistry using microglial-specific antibody OX-42. Microglia were activated by lipopolysaccharide (LPS) and interferon-${\gamma}$ (IFN-${\gamma}$) and the effect of curcumin or 6-gingerol on the microglial activation was examined. Specific parameters measured to monitor microglial activation were nitric oxide (NO), prostaglandin E$_2$(PGE$_2$) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) release. Curcumin (1~10 $\mu$M) inhibited NO release induced by LPS and IFN-${\gamma}$ in a dose-dependent manner whereas 6-gingerol (2~20 $\mu$M) did not have any effect on LPS/IFN-${\gamma}$-induced NO release. The levels of PGE$_2$and TNF-$\alpha$ induced by LPS and IFN-${\gamma}$ were also inhibited by 1~10 $\mu$M curcumin in a dose-dependent manner. These results showed that curcumin could modulate microglial activation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3987-3992
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• 2014

Curcumin, a polyphenol compound derived from the rhizome of the plant Curcuma longa L. has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms by which it induces apoptosis is limited. In this study, the anticancer efficacy of curcumin was investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that curcumin induced morphological changes and decreased cell viability. Apoptosis triggered by curcumin was visualized using Annexin V-FITC/7-AAD staining. Curcumin-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (MMP) and the release of cytochrome c into the cytosol. Furthermore, the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3 and increased cleaved PARP was observed in SGC-7901 cells treated with curcumin. Therefore, curcumin-induced apoptosis of SGC-7901 cells might be mediated through the mitochondria pathway, which gives the rationale for in vivo studies on the utilization of curcumin as a potential cancer therapeutic compound.

• Journal of Korean Neurosurgical Society
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• v.61 no.1
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• pp.10-18
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• 2018

Objective : To investigates the effect of curcumin on proliferation of spinal cord neural stem/progenitor cells (SC-NSPCs) and functional outcome in a rat spinal cord injury (SCI) model. Methods : Sixty adult male Sprague-Dawley rats were randomly and blindly allocated into three groups (sham control group; curcumin treated group after SCI; vehicle treated group after SCI). Functional recovery was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale during 6 weeks after SCI. The expression of SC-NSPC proliferation and astrogliosis were analyzed by nestin/Bromodeoxyuridine (BrdU) and Glial fibrillary acidic protein (GFAP) staining. The injured spinal cord was then examined histologically, including quantification of cavitation. Results : The BBB score of the SCI-curcumin group was better than that of SCI-vehicle group up to 14 days (p<0.05). The coimmunoreactivity of nestin/BrdU in the SCI-curcumin group was much higher than that of the SCI-vehicle group 1 week after surgery (p<0.05). The GFAP immunoreactivity of the SCI-curcumin group was remarkably lower than that of the SCI-vehicle group 4 weeks after surgery (p<0.05). The lesion cavity was significantly reduced in the curcumin group as compared to the control group (p<0.05). Conclusion : These results indicate that curcumin could increase the expression of SC-NSPCs, and reduce the activity of reactive astrogliosis and lesion cavity. Consequently curcumin could improve the functional recovery after SCI via SC-NSPC properties.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1465-1470
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• 2014

Inhibitor of DNA binding 1 (Id1) plays an important role in genesis and metastatic progression of prostate cancer. We previously reported that down regulation of Id1 by small interfering RNA could inhibit the proliferation of PC3 cells and growth of its xenografted tumors. Curcumin, the active ingredient of turmeric, has shown anti-cancer properties via modulation of a number of different molecular regulators. Here we investigated whether Id1 might be involved in the anti-cancer effects of curcumin in vivo and in vitro. We firstly confirmed that curcumin inhibited cell viability in a dose-dependent fashion, and induced apoptosis in PC3 cells, associated with significant decrease in the mRNA and protein expression of Id1. Similar effects of curcumin were observed in tumors of the PC3 xenografted mouse model with introperitoneal injection of curcumin once a day for one month. Tumor growth in mice was obviously suppressed by curcumin during the period of 24 to 30 days. Both mRNA and protein levels of Id1 were significantly down-regulated in xenografted tumors. Our findings point to a novel molecular pathway for curcumin anti-cancer effects. Curcumin may be used as an Id1 inhibitor to modulate Id1 expression.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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• pp.147-152
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• 2016

Present study aimed to investigate the effect of curcumin-pretreatment on intestinal I/R injury and on intestinal mucosa barrier. Thirty Wistar rats were randomly divided into: sham, I/R, and curcumin groups (n=10). Animals in curcumin group were pretreated with curcumin by gastric gavage (200 mg/kg) for 2 days before I/R. Small intestine tissues were prepared for Haematoxylin & Eosin (H&E) staining. Serum diamine oxidase (DAO) and tumor necrosis factor (TNF)-${\alpha}$ levels were measured. Expression of intestinal TNF-${\alpha}$ and tight junction protein (ZO-1) proteins was detected by Western blot and/or immunohistochemistry. Serum DAO level and serum and intestinal TNF-${\alpha}$ leves were significantly increased after I/R, and the values were markedly reduced by curcumin pretreatment although still higher than that of sham group (p<0.05 or p<0.001). H&E staining showed the significant injury to intestinal mucosa following I/R, and curcumin pretreatment significantly improved the histological structure of intestinal mucosa. I/R insult also induced significantly down-regulated expression of ZO-1, and the effect was dramatically attenuated by curcumin-pretreatment. Curcumin may protect the intestine from I/R injury through restoration of the epithelial structure, promotion of the recovery of intestinal permeability, as well as enhancement of ZO-1 protein expression, and this effect may be partly attributed to the TNF-${\alpha}$ related pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8931-8936
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• 2014

Background: Herbal compounds such as curcumin which decrease telomerase and gene expression have been considered as beneficial tools for lung cancer treatment. In this article, we compared the effects of pure curcumin and curcumin-loaded NIPAAm-MAA nanoparticles on telomerase and PinX1 gene expression in a lung cancer cell line. Materials and Methods: A tetrazolium-based assay was used for determination of cytotoxic effects of curcumin on the Calu-6 lung cancer cell line and telomerase and pinX1 gene expression was measured with real-time PCR. Results: MTT assay showed that Curcumin-loaded NIPAAm-MAA inhibited the growth of the Calu-6 lung cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of curcumin-loaded NIPAAm-MAA increased while expression of the PinX1 gene became elevated. Conclusions: The results showed that curcumin-loaded-NIPAAm-MAA exerted cytotoxic effects on the Calu-6 cell line through down-regulation of telomerase and stimulation of pinX1 gene expression. NIPPAm-MAA could be good carrier for such kinds of hydrophobic agent.

• Journal of Embryo Transfer
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• v.31 no.3
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• pp.299-305
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• 2016

Although cryopreservation of sperm is routinely used for clinical requirement, it has some problems, such as high generation of reactive oxygen species (ROS) and cold-shock. To reduce the detrimental damage in sperm, anti-oxidants were added to cryoprotectant for sperm. Curcumin is one of anti-oxidants, which are added in cryoprotectants. However, recent studies have demonstrated that curcumin decreases sperm viability and motility. This study was performed to identify the effect of curcumin on hydrogen peroxide ($H_2O_2$)-exposed bovine sperm, which were cryopreserved-thawed. In $H_2O_2$-exposed bovine sperm, reactive oxygen species (ROS) were significantly reduced by treatment with curcumin in a dose-dependent manner (p < 0.05). Among tested concentrations of curcumin (1 to $50{\mu}M$), 30 and $50{\mu}M$ curcumin showed anti-oxidant effect on $H_2O_2$-induced ROS generation. On the other hand, combination of 30 or $50{\mu}M$ curcumin with anti-oxidant $H_2O_2$ increased the percentage of apoptotic sperm compared to only $H_2O_2$ treatment. Sperm viability was also decreased in the combination of 30 or $50{\mu}M$ curcumin with $H_2O_2$ as judged by FDA/PI staining. $H_2O_2$-induced decrease in sperm progressive motility was recovered by treatment with $1{\mu}M$ curcumin. These results show that high concentration of curcumin has anti-oxidant effect, but it has also cytotoxic effect on bovine sperm. Sperm viability and motility might be more affected by cytotoxic signals of curcumin compared to antioxidant signals.

• International Journal of Oral Biology
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• v.40 no.2
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• pp.63-69
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• 2015

Curcumin (diferuloylmethane), a constituent of turmeric powder derived from the rhizome of Curcuma longa, has been shown to inhibit the growth of various types of cancer cells by regulating cell proliferation and apoptosis. However, a need exists to design more effective analogs because of curcumin's poor intestinal absorption. EF-24 (diphenyl difluoroketone), the monoketone analog of curcumin, has shown good efficacy in anticancer screens. However, the effects of curcumin and EF-24 on salivary gland epidermoid carcinoma cells are not clearly established. The main goal of this study was to investigate the effects of curcumin and EF-24 on cell growth and induction of apoptosis in human salivary gland epidermoid carcinoma cells. Our studies showed that curcumin and EF-24 inhibited the growth of HTB-41 cells in a dose- and time-dependent manner, and the potency of EF-24 was > 34-fold that of curcumin. Treatment with curcumin or EF-24 resulted in nuclear condensation and fragmentation in HTB-41 cells, whereas the control HTB-41 cell nuclei retained their normal regular and oval shape. Curcumin and EF-24 promoted proteolytic cleavages of procaspase-3/-7/-9, resulting in an increase in the amount of cleaved caspase-3/-7/-9 in the HTB-41 cells. Caspase-3 and -7 activities were detected in viable HTB-41 cells treated with curcumin or EF-24. These results suggest that the curcumin and EF-24 inhibit cell proliferation and induce apoptosis in HTB-41 human salivary gland epidermoid carcinoma cells, and that they may have potential properties as an anti-cancer drug therapy.

• Food Engineering Progress
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• v.21 no.3
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• pp.273-279
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• 2017

Curcumin have various health-beneficial properties in numerous studies. However, its bioavailability is low due to its limited intestinal uptake and rapid metabolism. This study aimed to evaluate the pharmacokinetics of newly developed sub-micron particle curcumin with increased water dispersibility (Theracurmin(R) CR-033P). Plasma curcumin levels were measured at 0, 1, 2, 4, 8 h after Theracurmin(R) CR-033P intake using high-performance liquid chromatography. For analyzing pharmacokinetics of Theracurmin(R) CR-033P, eighteen healthy subjects were recruited and received Theracurmin(R) CR-033P at a single oral dose containing curcumin 30 mg. $C_{max}$ was 28.14 ng/ml, and the area under the curve for 8 h was estimated to be 104.36 ng/ml. Based on the area under the plasma concentration (AUC), the bioavailability of sub-micron particle curcumin was higher 22-, 35-, 28-fold than native curcumin in men, women, and all subjects, respectively. For comparing by formulation, seven healthy subjects were recruited and received two type of treatment: (1) existing dosage form 300 mg (contained curcumin 30 mg) ${\times}$ 3 capsule, (2) high dosage form 300 mg (contained curcumin 90 mg) ${\times}$ 1 capsule + placebo 300 mg ${\times}$ 2 capsule. In the cross-over study, there was no significant differences in $C_{max}$ and AUC of plasma curcumin. In conclusion, submicron particle curcumin with increased water dispersibility significantly improved its oral bioavailability and women absorbed curcumin more effectively than men. Different formulation of Theracurmin(R) CR-033P has shown equivalent to the reference in terms of pharmacokinetics.

• Molecules and Cells
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• v.26 no.5
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• pp.486-489
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• 2008

Curcumin (diferuloylmethane), a pigment derived from turmeric, has anti-oxidant and anti-inflammatory activities. Accumulating evidence points to a biochemical link between increased oxidative stress and reduced bone density. Osteoclast formation was evaluated in co-cultures of bone marrow stromal cells (BMSC) and whole bone marrow cells (BMC). Expression of receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) was analyzed at the mRNA and protein levels. Exposure to curcumin led to dose-dependent suppression of osteoclastogenesis in the co-culture system, and to reduced expression of RANKL in $IL-1{\alpha}$-stimulated BMSCs. Addition of RANKL abolished the inhibition of osteoclastogenesis by curcumin, whereas the addition of prostaglandin $E_2$ ($PGE_2$) did not. The decreased osteoclastogenesis induced by curcumin may reduce bone loss and be of potential benefit in preventing and/or attenuating osteoporosis.