OBJECTIVE: To investigate the intervention of curcumin and its analogue J7 on oxidative stress injury in testis of type 2 diabetic rats. METHODS: Sixty male SD rats, 10 rats were chosen as normal control group (NC), the other 50 rats were assigned to experiment group. Experiment diabetic rats were induced by high-fat food and intraperitoneal injection of steptozotocin (STZ). After the model was established successfully, diabetic rats were divided into four groups randomly: diabetes mellitus group (DM, n=12), curcumin treatment group (CUR, n=10), high dose treatment group of J7 (J+, n=10), low dose treatment group of J7 (J-, n=10). The CUR group were intragastrically administered with curcumin 20 mg/kg daily, in addition, the J+ group and the J- group were intragastrically administered with J7 20 mg/kg and 10 mg/kg daily respectively. After 8 weeks, the fast blood glucose was detected biochemically. The activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were detected by hydroxylamine method and thiobarbituric acid method respectively. The protein expressions of the nuclear factor-erythroid 2-related factor 2 (tNrf2), phosphorylation of Nrf2 (pNrf2), catalase (CAT), NAD(P)H quinine oxidoreductase 1 (NQO1) were measured by Western blot. The mRNA expressions of CAT, NQO1, hemeoxygenase-1 (HO1) were measured by quantitative real-time PCR (qRT-PCR). Morphological structure of testis was observed by hematoxylin-eosin (HE) staining. The expressions of Nrf2 and CAT were also detected by immunohistochemical method. RESULTS: The levels of fast blood glucose and MDA in DM group were increased significantly(P＜0.05), while the body weight, the activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of CAT, NQO1, HO1 were decreased (P＜0.05). Under light microscope, the DM group showed disrupted histological appearance. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were decreased. With the treatment of curcumin and J7, the MDA levels in the three treatment groups were decreased (P＜0.05). The activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of NQO1, HO1 were increased (P＜0.05). the levels of fast blood glucose were decreased in the J+ and J- group (P＜0.05), and the mRNA expression of CAT was increased in the J+ group (P＜0.05). The ratio of pNrf2/tNrf2 in the J+ group was significantly higher than that in CUR and J- group (P＜0.05). The protein level of CAT in the J+ group was also significantly higher than that in J- group (P＜0.05). There were no significant differences in other indexes among the three treatment groups. Under light microscope, the morphology was obviously improved in the three treatment groups. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were increased in the three treatment groups. It was suggested that high dose J7 had better antioxidant stress ability in testis of diabetic rats. CONCLUSION Curcumin and J7 could inhibit the oxidative stress damage of testicular tissue in diabetic rats, which might be related with the activation of the Nrf2-ARE signaling pathway.
Animals ; Blood Glucose ; analysis ; Curcumin ; analogs & derivatives ; pharmacology ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2 ; Male ; Malondialdehyde ; metabolism ; NF-E2-Related Factor 2 ; metabolism ; Oxidative Stress ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Superoxide Dismutase ; metabolism ; Testis ; drug effects ; pathology

The dynamic accumulation rule of active substances in medicinal plants is of great value not only for medicinal material production and application,but also for the genetic mechanism study on the formation of medicinal ingredients,especially vital to guide medicinal material collection as well as experiment material selection and candidate gene screening in the analysis of biosynthesis pathway. This study investigated the accumulation of curcumins and terpenoids,and the biosynthesis of these metabolites,which are the active metabolites in Curcuma longa,a commonly used traditional Chinese medicine. Rhizoma of C. longa from leaf growing period,rhizome swelling period and dry matter accumulating period were used as experimental materials,to analyze the changes of metabolites and biosynthesis in the three periods by comparative transcriptome and metabolomes analysis.The results indicated that terpenoids accumulation and biosynthesis mainly occurred in leaf growing period,while curcumin accumulation and biosynthesis mainly occurred in dry matter accumulating period. Therefore,we suggested that turmeric rhizomes in leaf growth period were suitable for terpenoids biosynthetic pathway characterization,and rhizome in accumulation of dry matter period was suitable for curcuminoid biosynthesis pathway characterization. This study provides references for medicinal materialproduction and application,as well as biopathway analysis of active compounds for C. longa.
Curcuma ; chemistry ; Curcumin ; analysis ; Phytochemicals ; analysis ; Plants, Medicinal ; chemistry ; Rhizome ; chemistry ; Terpenes ; analysis

In this study, gas chromatography coupled with mass spectrometry(GC-MS) was used to analyze the changes of 12 kinds of cancer cells treated by curcumin. The related differential metabolites were screened and the metabolic pathways were analyzed to explore the anti-tumor mechanism of curcumin. Methyl thiazol tetrazolium(MTT) assay was used to detect the 50% inhibiting concentration(IC_(50)) of curcumin on 12 human tumor cells. After treatment with curcumin for 48 h, the cells were collected and analyzed by GC-MS, followed by pathway analysis and multivariate data analysis including principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA) and One-way analysis of variance(ANOVA),etc. Overall, 34 metabolites showed significant concentration changes after intervention for 48 h, mainly involving multiple metabolic pathways, including lysine degradation, glycine, serine and threonine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, aminoacyl-tRNA biosynthesis, primary bile acid biosynthesis, lysine biosynthesis. In this study, the anti-tumor mechanisms of curcumin interfering with energy metabolism, amino acid metabolism, microtubule system, protein synthesis and oxidative stress response of tumor cells were analyzed from the perspective of metabolism, providing a new reference for further tumor pharmacology study.
Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Curcumin ; pharmacology ; Gas Chromatography-Mass Spectrometry ; Humans ; Metabolic Networks and Pathways ; Metabolome ; Metabolomics ; Principal Component Analysis

Turmeric residue (TR), containing residual levels of curcumin, is a solid by-product waste generated after the extraction and separation of curcumin from turmeric root. A feeding trial was conducted to evaluate the effects of TR on the survival of Chinese soft-shelled turtles (SSTs), Pelodiscus sinensis, under a high ambient temperature. A total of 320 female SSTs were assigned randomly to two diets: basal diet (the control group, n=160) and an interventional diet supplemented with 10% TR (the TR group, n=160). Our results demonstrated that supplementation of TR increased the SST survival rate by 135.5%, and superoxide dismutase (SOD) activity of SST liver by 112.8%, and decreased the malondialdehyde (MDA) content of SST liver by 36.4%, compared to the control group. The skin of the SST fed TR showed a golden color. High-performance liquid chromatography (HPLC) analysis indicated that the concentrations of curcumin in TR and the skin of the SST fed TR were (1.69±0.30) and (0.14±0.03) μg/g, respectively. Our observation suggests that supplementation of TR increased the survival rate of SST under high ambient temperatures. We speculated that the increased survival rate and tolerance at the high ambient temperature were associated with the anti-oxidation activity of curcumin from TR. Moreover, curcumin in TR could be deposited in SST skin, which made it more favored in the market of China. Our findings provide new knowledge and evidence to effectively reuse TR as a feed additive in animal and aquatic farming.
Animal Feed ; Animals ; Antioxidants/pharmacology* ; Body Weight/drug effects* ; Chromatography, High Pressure Liquid ; Curcuma ; Curcumin/analysis* ; Dietary Supplements ; Female ; Hot Temperature ; Plant Extracts/pharmacology* ; Superoxide Dismutase/metabolism* ; Survival Rate ; Turtles/physiology*

OBJECTIVE: The present study explored the three-dimensional spatial arrangements of the neurons and glial cells within the medial prefrontal cortex (mPFC) of rats. METHODS: It evaluated the arrangement for differences after stress with or without treatment with curcumin and sertraline using second-order stereology. Orientator method was applied to obtain isotropic uniform random sections of mPFC. The pair correlation g(r) and cross-correlation functions were estimated by counting dipole probes superimposed on histological sections of mPFC. RESULTS: The mean total volume of neurons and glial cells was 0.80 (0.05) and 0.40 (0.07), respectively in the control group. The corresponding values decreased by 50% in the stressed group. The curve of g(r) for the neurons and glial cells showed a wider gap between the stressed rats' mPFC. Theses indicate a negative correlation (repulsion) between the neurons and glial cells in the stressed rats. Evaluation of the cross-correlation function of the neurons and glial cells also showed a negative correlation in the stressed group. The estimated values of the global degree of order in the spatial point pattern for neurons and glial cells were 0.62 and 0.20 in control and stressed animals, respectively. Curcumin and sertraline protected the spatial arrangements of the cells after stress induction in rats. In addition, the volume of the neurons and glial cells remained unchanged after stress. CONCLUSION: Dissociation of the neurons and glial cells can is seen at some places in the stressed rats' cortex. However, the spatial arrangement of the cells was remained unchanged in curcumin+stress and sertraline+stress rats.
Animals ; Cerebral Cortex ; Curcumin* ; Neuroglia* ; Neurons* ; Prefrontal Cortex* ; Rats ; Sertraline* ; Spatial Analysis

To study the in vitro anti-angiogenesis effect of three curcumin pigments (curcumin, demethoxycurcumin, bisdemethoxycurcumin). In the study, the inhibitory effect of the three curcumin pigments on proliferation of HUVEC cells induced by OX-LDL and the effect on migration of HUVEC cells were detected. The effect on neovascularization was observed by chorioallantoic membrane (CAM) test. The effect on cell adhesion factors ICAM-1 and VCAM-1 of HUVECs were tested by Real-time RT-PCR. It was found that the three curcumins could inhibit the proliferation of HUVEC cells induced by OX-LDL within the dosage range 4, 8, 16 mg x L(-1), with a dose-dependence. The proliferative effect of curcumins on HUVECs was greater than the other two derivatives (P < 0.01). All of the three curcumin pigments inhibited the migration of HUVEC cells and the angiogenesis of chick chorioallantoic membrane (CAM). The migration inhibition rate of curcumins at middle and high concentrations was greater than the other two (P < 0.01). All of the three curcumin could down-regulate the expression of VEGF and ICAM-1, and curcumins showed more obvious effect in down-regulating VEGF than demethoxycurcumin and bisdemethoxycurcumin(P < 0.01); Bisdemethoxycurcumin showed the most significant effect in down-regulating ICAM-1 (P < 0.01). All of the three showed no remarkable effect on expression of VCAM-1, and only bisdemethoxycurcumin showed the down-regulating effect (P < 0.05). According to the findings, all of the three curcumin pigments could resist angiogenesis by inhibiting proliferation and migration of endothelial cells and down-regulating the expression of VEGF and adhesion molecules ICAM-1.
Angiogenesis Inhibitors ; pharmacology ; Animals ; Cell Movement ; drug effects ; Cells, Cultured ; Chorioallantoic Membrane ; drug effects ; Curcumin ; analogs & derivatives ; pharmacology ; Humans ; Intercellular Adhesion Molecule-1 ; genetics ; RNA, Messenger ; analysis ; Vascular Cell Adhesion Molecule-1 ; genetics ; Vascular Endothelial Growth Factor A ; genetics

Whether supplementation of curcuminoids decreases serum adipocyte-fatty acid binding protein (A-FABP) level and whether this decrease benefits glucose control is unclear. One-hundred participants (n=50 administered curcuminoids, n=50 administered placebo) from our previous report on the effect of curcuminoids on type 2 diabetes in a 3-month intervention were assessed for levels of serum A-FABP, oxidative stress, and inflammatory biomarkers. Curcuminoids supplementation led to significant decreases in serum A-FABP, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 levels. Curcuminoids supplementation also significantly increased serum superoxide dismutase (SOD) activity. The change in serum A-FABP levels showed positive correlations with changes in levels of glucose, free fatty acids (FFAs), and CRP in subjects supplemented with curcuminoids. Further stepwise regression analysis showed that A-FABP was an independent predictor for levels of FFAs, SOD, and CRP. These results suggest that curcuminoids may exert anti-diabetic effects, at least in part, by reductions in serum A-FABP level. A-FABP reduction is associated with improved metabolic parameters in human type 2 diabetes.
Biomarkers ; blood ; Blood Glucose ; analysis ; Curcumin ; administration & dosage ; pharmacology ; therapeutic use ; Diabetes Mellitus, Type 2 ; blood ; complications ; drug therapy ; immunology ; Fatty Acid-Binding Proteins ; blood ; Humans ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; therapeutic use ; Obesity ; blood ; complications ; drug therapy ; immunology ; Oxidative Stress ; drug effects ; immunology ; Treatment Outcome

The paper is aimed to study the dynamic accumulation regulation of curcumin (Cur), demethoxycurcumin (DMC) and bisdemethoxyeurcumin (BDMC) in three strains of Curcuma longa, and provide scientific references for formalized cultivation, timely harvesting, quality control and breeding cultivation of C. longa. The accumulation regulation of the three curcumin derivatives was basically the same in rhizome of three strains. The relative contents decreased along with plant development growing, while the accumulation per hectare increased with plant development growing. The accumulation of curcuminoids per hectare could be taken as the assessment standard for the best harvest time of C. longa. A3 was the best strain in terms of Cur and BDMC content.
Curcuma ; chemistry ; growth & development ; metabolism ; Curcumin ; analogs & derivatives ; analysis ; metabolism ; Quality Control ; Rhizome ; chemistry ; growth & development ; metabolism

OBJECTIVETo study the effects of curcumin on vascular endothelial injuries induced by radiation and the mechanism.

METHODSHuman umbilical vein endothelial cells (HUVEC) were isolated, cultured and divided into the control group and 4 groups exposed to 3-ray at the doses of 2, 4, 6 and 8 Gy. Cellular morphological and ultrastructural changes were examined under light microscopy and electron microscopy respectively. Flow cytometry was used to detect the cellular apoptosis, necrosis and intracellular reactive oxygen species(ROS) generation. The contents of Lactate dehydrogenase (LDH) and malondialdehyde (MDA) in the cultures were measured before and after irradiation.

RESULTSThe results of cellular morphological and ultrastructural ex-aminations shown that the typical apoptotic changes appeared after irradiation. The rates of apoptosis and necrosis in groups pretreated with curcumin were significantly lower than those in other groups (P<0.05). LDH and MDA in the irradiation groups were significantly higher than those in curcumin pretreatment groups (P<0.05). The ROS generation in radiation groups significantly increased with the radiation doses, as compared with the groups pre-treated with curcumin (P<0.05).

CONCLUSIONIrradiation induced the apoptosis and necrosis of HUVEC, and increased significantly the intracellular LDH and MDA levels in a dose-dependent. Curcumin had the protective effects on HUVEC from the apoptosis and necrosis induced by radiation.

Apoptosis ; drug effects ; radiation effects ; Curcumin ; pharmacology ; Human Umbilical Vein Endothelial Cells ; drug effects ; radiation effects ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Malondialdehyde ; metabolism ; Reactive Oxygen Species ; analysis ; Vascular System Injuries

OBJECTIVEThis study examined the effects of curcumin on intestinal histopathological changes, cyclooxygenase-2 (COX-2) expression, and tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) concentrations in neonatal rats with necrotizing enterocolitis (NEC), in order to investigate the effects of curcumin against NEC.

METHODSForty neonatal rats were randomly divided into four groups (n=10 each): normal control, solvent control, NEC model, and curcumin intervention. The general situations of rats were observed for 3 consecutive days, and the rats were then sacrificed on the 4th day. Intestinal tissues were obtained for examining the histopathological changes, COX-2 expression, and TNF-alpha and IL-10 concentrations.

RESULTSCurcumin treatment ameliorated the general situations and histopathological signs in rats with NEC. TNF-alpha and IL-10 concentrations in the NEC model and the curcumin intervention groups increased significantly compared with those in the normal and solvent control groups (p<0.05). The concentration of TNF-alpha decreased (p<0.05), while the concentration of IL-10 increased significantly in the curcumin intervention group in comparison with the NEC model group (p<0.05). Immunohistochemistry results indicated that the positive expression of COX-2 in the curcumin intervention group was significantly lower than that in the NEC model group.

CONCLUSIONSCurcumin has protective effects against NEC in neonatal rats, possibly through inhibiting COX-2 expression, reducing TNF-alpha content, and increasing IL-10 content.

Animals ; Animals, Newborn ; Body Weight ; Curcumin ; therapeutic use ; Cyclooxygenase 2 ; analysis ; physiology ; Disease Models, Animal ; Enterocolitis, Necrotizing ; drug therapy ; pathology ; Female ; Interleukin-10 ; analysis ; Intestines ; pathology ; Male ; NF-kappa B ; physiology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; analysis