Low-dose Curcumin Group Research Articles

Curcumin Improved Intestinal Epithelial Barrier Integrity by Up-Regulating ZO-1/Occludin/Claudin-1 in Septic Rats.

Objective To investigate the protective effect and mechanism of curcumin on intestinal barrier function in rats with enterogenic sepsis. Methods Rats were divided into Sham group (Sham), Model group (Model), low-dose curcumin group (100 mg/kg), and high-dose curcumin group (200 mg/kg), with 10 rats in each group. Sepsis model was established in model group, low-dose curcumin group, and high-dose curcumin group. After drug intervention, hematoxylin-eosin (HE) staining was used to observe the histopathological changes of small intestine in each group. The levels of TNF-α, IL-1β, and IL-6 in serum and intestinal tissues of rats were determined by ELISA. The expression of ZO-1, occludin, and claudin-1 in ileum was detected by QRT-PCR and Western blot. Western blotting was used to detect the expression of ERK/JNK signaling pathway, NF-κB p65, apoptosis-related proteins Caspase-3, and TNF-α in rat intestinal tissues. Results HE staining showed that curcumin treatment reduced epithelial cell shedding, interstitial edema, and apoptosis. Compared with model group, DAO activity, serum intestinal fatty acid binding protein (I-FABP), TNF-α, IL-6, and IL-1β expression in curcumin group were decreased in a dose-dependent manner. Curcumin can upregulate the mRNA and protein expression levels of ZO-1, occludin, and claudin-1 in ileum of CLP-induced rats. In addition, curcumin inhibits NF-κB p65 activation and apoptosis by regulating ERK/JNK signaling pathway. Conclusion Curcumin can reduce inflammatory response and upregulate the expression of intestinal tight junction proteins ZO-1, occludin, and claudin-1 in rats with enterogenic sepsis, and protect intestinal barrier function.

Effects of curcumin on oxidative stress, inflammation and apoptosis in L-arginine induced acute pancreatitis in mice

Background and purposeCurcumin, an active constituent of rhizomes of Curcuma longa Linn, exhibits a variety of biological activities such as anti-inflammation and anti-oxidant. The present study aims to examine the effects of curcumin on oxidative stress, inflammation and apoptosis in L-arginine induced acute pancreatitis (AP) in mice. MethodsMale ICR mice were randomly divided into 4 groups. Control group received intraperitoneal injection (i.p.) of 1% DMSO as a vehicle. AP group received two doses of i.p. L-arginine (L-Arg) 450 mg/100 g body weight (BW) at 1-hour interval. AP plus low-dose curcumin group received i.p. curcumin 50 mg/kg BW 1 hour before L-Arg injection and then once daily for 3 days. AP plus high-dose curcumin group received i.p. curcumin 200 mg/kg BW 1 hour before L-Arg injection and then once daily for 3 days. All mice were sacrificed at 72 hours. Pancreatic tissue was obtained for histological evaluation, immunohistochemical studies for nuclear factor-kappa beta (NF-kβ), apoptosis and myeloperoxidase (MPO), and Western blot analyses for 4-Hydroxynonenal (4-HNE). Blood samples were collected for amylase analysis. ResultsMean body weight was significantly lower in AP group than in control group, while in curcumin group, body weight was maintained. The serum amylase, number of MPO positive cells, NF-kB positive cells, TUNEL positive cells, and 4-HNE expression significantly increased in AP group when compared with control group, but decreased in low and high-dose curcumin groups. Mice in AP group developed severe pancreatic inflammation, edema and fat necrosis. While mice in low and high-dose curcumin groups showed a significant improvement in histopathological scores. There was no significant difference between low and high doses of curcumin. ConclusionCurcumin could attenuate acute pancreatitis via anti-oxidant, anti-inflammation and anti-apoptosis property leading to the improvement in pancreatic damage.

Effect of curcumin on lidocaine-induced nerve injury in rats: the role of Akt and ERK1/2 signaling pathway

Objective To evaluate the effect of curcumin on lidocaine-induced nerve injury and the role of protein kinase B (Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway in rats. Methods Eighty SPF male Sprague-Dawley rats, aged 8-10 weeks, weighing 220-250 g, were divided into 8 groups (n=10 each) using a random number table method: control group(group C), sham operation group(group S), lidocaine group (group L), dimethyl sulfoxide (DMSO) group, low-dose curcumin group (group CL), high-dose curcumin group (group CH), curcumin plus ERK inhibitor PD98059 group (group P) and curcumin plus Akt inhibitor MK-2206 group (group M). The model of nerve injury was established by injecting 2% lidocaine 10 μl via the catheter in anesthetized rats in the other six groups except for C and S groups.Drugs were injected through a microcatheter for 14 consecutive days starting from 3rd day after IT catheterization as follows: DMSO 10 μl, curcumin 100 μg/10 μl and curcumin 500 μg/10 μl were injected once a day in D, CL and CH groups, respectively; curcumin 500 μg/10 μl was injected once a day, and D98059 10 μg and MK-2206 12 μg (in 5 μl DMSO) were intraperitoneally injected once a week in P and M groups, respectively.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal threshold (TWL) on the operated side were measured on 1 day before IT catheterization, before administration on 3rd day after IT catheterization, and on 14th day after administration.The spinal cord was removed on 1st day after the end of administration for determination of the expression of ERK1/2, phosphorylated ERK1/2 (p-ERK1/2), Akt, phosphorylated Akt (p-Akt), c-fos, Bcl-2 and Bax (by Western blot) and expression of ERK1/2 and Akt mRNA (by real-time polymerase chain reaction). Results Compared with group C, the MWT was significantly decreased, the TWL was shortened, the expression of ERK1/2 protein and mRNA, p-ERK1/2, c-fos, Akt protein and mRNA, p-Akt and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group L (P<0.05). Compared with group L, the MWT was significantly increased, and the TWL was prolonged in CL, CH, P and M groups, the expression of p-ERK1/2, c-fos, p-Akt and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in CL and CH groups, the expression of p-Akt and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in group P, and the the expression of p-ERK1/2 and c-fos was up-regulated in group M (P<0.05). Compared with group CH, the MWT was significantly decreased, and the TWL was shortened in P and M groups, the expression of p-ERK1/2 and c-fos was down-regulated in group P, and the expression of p-Akt and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group M (P<0.05). Conclusion Curcumin can reduce lidocaine-induced nerve injury, and the mechanism may be partly related to enhancing the activity of Akt and ERK1/2 signaling pathway in rats. Key words: Curcumin; Lidocaine; Drug-related side effects and adverse reactions; MAP kinase signaling system

Effects of curcumin on glioma cell U87 and its effects on cysteinyl aspartate-specific protease-3, cysteinyl aspartate-specific protease-9, B cell lymphoma/leukemia-2 and B cell lymphoma/leukemia-2 associated X protein

Objective To explore the effects of curcumin on glioma cell U87 and its effects on cysteinyl aspartate-specific protease (Caspase)-3, Caspase-9, B cell lymphoma/leukemia-2 (bcl-2) and bcl-2 associated X protein (bax). Methods The U87 cells were treated with curcumin solution. Methyl thiazol tetrazolium (MTT) assay was used to measure cell proliferation. Flow cytometry was used to examine cell apoptosis. Enzyme-linked immunosorbent assay was used to detect Caspase 3 and Caspase 8 levels in cell culture medium. Western blotting was used to detect the expression of bcl-2 and bax proteins. Results The proliferative rate of U87 cells at 24 h and 48 h in low dose curcumin group [(8.48±1.19)% and (11.89±1.39)%] and high dose curcumin group [(16.04±1.58)% and (25.63±1.66)%] was significantly lower than that in blank control group [(1.47±0.10)% and (1.39±0.19)%] (P<0.05). The proliferative rate of U87 cells at 24 h and 48 h cells in high dose curcumin group was significantly lower than that in low dose curcumin group (P<0.05). The proliferative rate of U87 cells at 48 h in high dose curcumin group and low dose curcumin group was significantly lower than that at 24 h in the corresponding groups (P<0.05). The apoptosis rate of U87 cells in low dose curcumin group and high dose curcumin group [(9.53±1.21)% and (20.52±2.35)%] was significantly higher than that in blank control group (2.22±0.14)% (P<0.05). The apoptosis rate of U87 cells in high dose curcumin group was significantly higher than that in low dose curcumin group (P<0.05). Caspase-3 and Casepase-8 levels in cell culture supernatant of low dose curcumin group [(156.35±29.63) and (158.35±25.36) ng/ml], and high dose curcumin group [(252.52±35.21) and (225.61±30.66) ng/ml] were significantly higher than those of blank control group [(50.63±10.36) and (78.23±11.35) ng/ml, P<0.05]. Caspase-3 and Casepase-8 levels in cell culture supernatant of high dose curcumin group were significantly higher than those of low dose curcumin group (P<0.05). The expression level of bcl-2 protein in U87 cells of low dose curcumin group (0.61±0.10 and 0.67±0.09) and high dose curcumin group (0.42±0.08 and 0.88±0.11) was significantly lower than that of blank control group (0.88±0.16 and 0.33±0.04), and that of bax protein in low dose curcumin group and high dose curcumin group was significantly higher than that of blank control group (P<0.05). The expression level of bcl-2 protein in U87 cells of high dose curcumin group was significantly higher than that of low dose curcumin group, and that of bax protein was significantly higher in low dose curcumin group and high dose curcumin group than that in blank control group (P<0.05). Conclusion Curcumin can inhibit the proliferation and promote the apoptosis of U87 glioma cells by promoting the expression of Caspase-3 and Caspase-8 and altering the expression of bcl-2 and bax. Key words: Curcumin; Glioma; Cysteinyl aspartate-specific protease-3; Cysteinyl aspartate-specific protease-9; B cell lymphoma/leukemia-2; B cell lymphoma/leukemia-2 associated X protein

Effects of Curcumin on the Expression of Flotillin-1 in the Brains of APP/PS1 Double Transgenic Mice

Alzheimer’s Disease (AD) is a chronic and progressive neurodegenerative disease. Flotillin-1 is a marker protein of lipid raft in nervous tissue, which is significantly increased in AD. To investigate the changes of flotillin-1 expression in the brains of APP/PS1 double transgenic mice treated with curcumin, thirty six-month-old APP/PS1 double transgenic mice were randomly divided into model group (MOD), low-dose curcumin group (LCUR) and high-dose curcumin group (HCUR). LCUR group mice and HCUR group mice were fed with curcumin (0.16 g.kg-1 and 1.0 g.kg-1, respectively) every day for 6 months. Western blot and real-time PCR were used to detect the expression of flotillin-1 in brain. Results showed that compared with MOD group, the expression of flotillin-1 protein (P P

Effect of cuecumin on mammalian target of rapamyein signaling pathway during ischemia-reperfusion injury in isolated rat lungs

Objective To evaluate the effect of curcumin on the mammalian target of rapamyein(mTOR)signaling pathway during ischemia-reperfusion(I/R)injury in isolated rat lungs. Methods Sixty-four clean-grade healthy male Sprague-Dawley rats, aged 3-4 months, weighing 250-320 g, were divided into 4 groups(n=16 each)using a random number table method: sham operation group(S group), I/R group, low-dose curcumin group(LC group)and high-dose curcumin group(HC group). The rats only received in vitro perfusion without ischemia in S group.Isolated rat lungs were subjected to 60 min of ischemia followed by 75-min reperfusion to establish the lung I/R injury model in I/R group.Curcumin 5 and 10 μmol/L were added to perfusion fluid from the beginning of reperfusion in LC and HC groups, respectively.Airway resistance(Res), lung compliance, perfusion flow(Flow)and pulmonary venous partial pressure of oxygen(PaO2)were recorded at 10 min of first perfusion(T0)and 15, 45 and 75 min of reperfusion(T1-3). Wet/dry lung weight ratio(W/D ratio)was measured at the end of reperfusion.The morphological structure and ultrastructure of lung tissues were observed by using a light microscope and a transmission electron microscope, respectively.The expression of mTOR, Tau protein, nuclear factor kappa B(NF-κB)and tumor necrosis factor-alpha(TNF-α)mRNA in lung tissues was detected by real-time polymerase chain reaction.The expression of mTOR, phosphorylated Tau protein(pS396 Tau protein), NF-κB and TNF-α protein in lung tissues was determined by Western blot. Results Compared with S group, Res at T1-3 and W/D ratio at T3 were significantly increased, lung compliance, Flow and PaO2 were decreased at T1-3, and the expression of mTOR, NF-κB and TNF-α protein and mRNA, Tau protein mRNA and pS396 Tau protein was up-regulated at T3 in I/R, LC and HC groups(P<0.05). Compared with I/R group, Res at T1-3 and W/D ratio at T3 were significantly decreased, lung compliance, Flow and PaO2 were increased at T1-3, and the expression of mTOR, NF-κB and TNF-α protein and mRNA, Tau protein mRNA and pS396 Tau protein was down-regulated at T3 in LC and HC groups(P<0.05). Compared with LC group, Res at T1-3 and W/D ratio at T3 were significantly decreased, lung compliance, Flow and PaO2 were increased at T1-3, and the expression of mTOR, NF-κB and TNF-α protein and mRNA, Tau protein mRNA and pS396 Tau protein was down-regulated at T3 in HC group(P<0.05). The microscopic examination showed that the injury to lung tissues was significantly attenuated in LC and HC groups as compared with I/R group. Conclusion The mechanism by which curcumin reduces I/R injury in isolated rat lungs is related to inhibiting mTOR signaling pathway. Key words: Curcumin; Lung; Reperfusion injury; Protein kinase C

Effect and its molecular mechanisms of curcumin on pulmonary artery smooth muscle cells in rat model with chronic obstructive pulmonary disease

Objective: To investigate the effects and the underlying molecular mechanisms of curcumin on pulmonary artery smooth muscle cells in rat model with chronic obstructive pulmonary disease (COPD). Methods: A total of 75 male Wistar rats were randomly divided into control group (group CN), model group (group M), low-dose curcumin group (group CL), medium-dose curcumin group (group CM) and high-dose curcumin group (group CH). HE staining was used to observe the morphology of pulmonary artery. Proliferating cell nuclear antigen (PCNA), apoptosis-related protein Bcl-2 and Bax were detected by immunohistochemical staining. TUNEL kit was used to analyze the effects of curcumin on apoptosis of smooth muscle cells, and the protein expressions of SOCS-3/JAK2/STAT pathway in lung tissues were determined by western blot. Results: Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVMI) in group M were significantly higher than those in group CN, group CH and group CM (all P<0.05). HE staining and TUNEL kit test showed that the number of pulmonary artery smooth muscle cells had a significant increase in group M, while the pulmonary artery tube became thin, and the smooth muscle cells shrinked in group CM and group CH. Immunohistochemistry showed that PCNA and Bcl-2 in group M were significantly higher than those in group CN (all P<0.05), while Bax expression was significantly lower than that in group CN (P<0.05). PCNA in group CM and group CH were significantly lower than that in group M (all P<0.05), while Bax expression was significantly higher than that in group M (P<0.05). Western blot showed that SOCS-3 protein was significantly decreased in group M, while the p-JAK2, p-STAT1, p-STAT3 were significantly increased (all P<0.05). Compared with group M, SOCS-3 protein in group CM and group CH were significantly increased (all P<0.05), while the p-JAK2, p-STAT3 were significantly reduced (all P<0.05). Conclusion: Curcumin could promote the apoptosis of smooth muscle cells in rats with COPD, and improve the mean pulmonary artery pressure and RVMI through stimulating SOCS-3/JAK2/STAT signaling pathway.

Effect of crucumin on vascular endothelial function in atherosclerotic rabbits

To observe the effect of curcumin on nitric oxide (NO) in plasma of atherosclerotic rabbits, activity of constitutive nitric oxide synthase (cNOS) and asymmetric dimethylarginine (ADMA), and discuss curcumin's effect against AS and its correlation with ADMA. Thirty-eight male Japanese white rabbits were randomly divided into four groups: the control group (eight rabbits fed with standard diets), the model group (ten rabbits fed with high-fat diets), the low dose curcumin group (ten rabbits fed with high-fat diets and 100 mg . kg-1 d -1 ) and the high dose curcumin group (ten rabbits fed with high-fat diets and 200 mg kg-1 d-1 curcumin). At the end of the 12th week, their plasmas were tested for TC, LDL-C, NO, endothelin (ET) , ADMA and activity of aortic cNOS. Aortic tissues were collected for histological examinations. The three groups fed with high-fat diets showed higher plasma ADMA and ET than the control group (P <0. 01) , but with decrease in plasma NO concentration and arterial cNOS activity (P <0. 01). Compared with the model group (P <0. 05) , the curcumin groups showed lower plasma ADMA and ET (P <0. 05), but higher plasma NO concentration and arterial cNOS activity than the model group (P <0. 01). There was no significant difference between the two curcumin groups. Curcumin may play an important protective role in AS process by reducing plasma ADMA level. [Key words] atherosclerosis; asymmetric dimethylarginine; crucumin; nitric oxide; nitric oxide synthase

Therapeutic Advantages of Treatment of High-Dose Curcumin in the Ovariectomized Rat

ObjectiveAlthough curcumin has a protective effect on bone remodeling, appropriate therapeutic concentrations of curcumin are not well known as therapeutic drugs for osteoporosis. The purpose of this study was to compare the bone sparing effect of treatment of low-dose and high-dose curcumin after ovariectomy in rats.MethodsForty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed among three groups; untreated OVX group, low-dose (10 mg/kg) curcumin administered group, and high-dose (50 mg/kg) curcumin group. At 4 and 8 weeks after surgery, serum biochemical markers of bone turnover were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae were determined by micro-computed tomography (CT). In addition, mechanical strength was determined by a three-point bending test.ResultsHigh-dose curcumin group showed significantly lower osteocalcin, alkaline phosphatase, and the telopeptide fragment of type I collagen C-terminus concentration at 4 and 8 weeks compared with the untreated OVX group as well as low-dose curcumin group. In the analyses of micro-CT scans of 4th lumbar vertebrae, the high-dose curcumin treated group showed a significant increase in bone mineral densities (p=0.028) and cortical bone mineral densities (p=0.036) compared with the low-dose curcumin treated group. Only high-dose curcumin treated group had a significant increase of mechanical strength compared with the untreated OVX group (p=0.015).ConclusionThe present study results demonstrat that a high-dose curcumin has therapeutic advantages over a low-dose curcumin of an antiresorptive effect on bone remodeling and improving bone mechanical strength.

Preliminary study on mechanism of therapeutic effect of Huganjiexian decoction on hepatic fibrosis

To observe the effects of Huganjiexian decoction on rat hepatic fibrosis and the creation of cytokines. Rat hepatic fibrosis was induced by intraperitoneally injection of carbon tetrachloride. At the same time, these rats were treated with different dosages of Huganjiexian decoction. Sho-saiko-to compound treating group and Fufangbiejiarangan Tablets treating group were used as positive controls. After twelve weeks, all rats were executed. Histopathologic changes were observed after H.E and Masson stainings. The expression of collagen type I, collagen type III, TGF-beta 1 and PDGF-BB in liver were detected by immunohistochemical staining. Compared with fibrotic group, hepatic fibrosis in decoction groups was significantly improved. In decoction groups, levels of collagen type I, collagen type III, TGFbeta1 and PDGF-BB were decreased, especially in the low-dose curcumin group. The TGF-beta 1 positive percentage were 7.56%+/-2.18%, 29.25%+/-7.84%, 13.54%+/-4.15%, 21.82%+/-6.64%, 20.06%+/-7.14%, 13.78%+/-4.35%, 12.75%+/-3.98% in liver tissues from normal group, model group, low, middle, high curcumin, Sho-saiko-to compound and Fufangbiejiarangan Tablets treating groups respectively (P less than 0.05); while the PDGF-BB positive percentage were 1.68%+/-0.41%, 11.70%+/-2.28%, 3.65%+/-0.76%, 5.24%+/-1.04%, 6.37%+/-1.12%, 4.16%+/-0.61%, 3.38%+/-0.56% in liver tissues from those groups respectively (P less than 0.05). Huganjiexian decoction can improve rat hepatic fibrosis, possibly via inhibiting the expression of collagen type I, collagen type III, TGFbeta1 and PDGF-BB.

Curcumin prevents liver fibrosis by inducing apoptosis and suppressing activation of hepatic stellate cells

This study was designed to investigate the prophylactic effects and the mechanisms of curcumin on liver fibrosis in rats. Liver fibrosis was induced in 72 Sprague Dawley rats by intraperitoneal injection of carbon tetrachloride. Rats were divided into control, liver fibrosis, high, medium, and low dose curcumin (200, 100, and 50 mg kg(-1), respectively), and colchicine (0.1 mg kg(-1)) groups. After 8 weeks of treatment, histopathological examination was performed on hepatic tissues, and liver fibrosis was graded. Hepatic stellate cells activity was examined by smooth muscle alpha-actin immunohistochemistry staining, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling. The liver fibrosis score in the high, medium, and low dose curcumin group (5.79 +/- 1.80, 8.58 +/- 3.34, and 9.58 +/- 3.32, respectively) and the colchicine group (4.91 +/- 1.28) was significantly lower than in the fibrosis group (20.40 +/- 3.38, P < 0.01). The ratio of activated hepatic stellate cells in the three curcumin groups (0.97 +/- 0.69, 2.06 +/- 0.58, and 3.49 +/- 1.03, respectively) and the colchicine group (0.78 +/- 0.31) was significantly lower than in the fibrosis group (6.08 +/- 1.13, P < 0.05). The apoptosis index in the three curcumin groups (0.57 +/- 0.21, 0.37 +/- 0.22, and 0.34 +/- 0.21, respectively) was higher than in the fibrosis (0.09 +/- 0.09, P < 0.05) or the colchicine group (0.16 +/- 0.19, P < 0.05). Curcumin prevents carbon tetrachloride-induced liver fibrosis in rats. The prevention of liver fibrosis may be due to the inhibition of the activation of hepatic stellate cells and induction of their apoptosis.

Curcumin ameliorates acute thioacetamide‐induced hepatotoxicity

Increased production of reactive oxygen species and nitric oxide and activation of nuclear factor kappa B are implicated in the pathogenesis of various liver diseases, including fulminant hepatic failure. Curcumin is a naturally occurring anti-oxidant that reduces oxidative stress and inhibits nuclear factor kappa B and nitric oxide formation. The aim of the present study is to assess curcumin's therapeutic potential in acute thioacetamide hepatotoxicity, a rat model of fulminant hepatic failure. Fulminant hepatic failure was induced by two intraperitoneal (i.p.) injections of 300 mg/kg thioacetamide (TAA) at 24-h intervals. The experimental groups received a low-dose (200 mg/kg per day, i.p.) or a high-dose (400 mg/kg per day) of curcumin, initiated 48 h prior to the first TAA injection. A fourth group was administered neither TAA nor curcumin and served as a control. The survival rate was higher in both curcumin-treated groups compared to the TAA only treated group. Biochemical parameters of liver injury, blood ammonia and hepatic necroinflammation were lower in the low-dose curcumin group compared to TAA controls, and were further reduced in the high-dose group (P < 0.05 and P < 0.01, respectively). Curcumin treatment also reduced the TAA-induced elevated hepatic levels of thiobarbituric acid-reactive substances (TBARS), and inhibited the nuclear binding of nuclear factor kappa B (NFkappaB) and inducible nitric oxide (iNOS) protein expression. Curcumin improved survival and minimized oxidative stress, hepatocellular injury and hepatic necroinflammation, NFkappaB binding and iNOS expression in a rat model of FHF. These findings support the role of ROS, NFkappaB and iNOS in mediating liver insult due to TAA, and that of curcumin as a hepato-protectant.