Indian Journal of Medical Research

: 2011  |  Volume : 134  |  Issue : 5  |  Page : 717--724

Preventive action of curcumin in experimental acute pancreatitis in mouse

Wen-Guang Yu1, Gang Xu2, Gui-Jie Ren1, Xia Xu1, Hui-Qing Yuan1, Xiao-Li Qi1, Ke-Li Tian1,  
1 Department of Biochemistry & Molecular Biology, Shandong University School of Medicine, Shandong, PR China
2 Department of Gastroenterology, 456 Hospital of PLA, Shandong, PR China

Correspondence Address:
Ke-Li Tian
Department of Biochemistry & Molecular Biology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan 250012, Shandong
PR China


Background & objectives: Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. The purpose of the present study was to investigate the preventive effects of curcumin against acute pancreatitis (AP) induced by caerulein in mouse and to elucidate possible mechanism of curcumin action. Methods: Curcumin (50 mg/kg/day) was intraperitoneally injected to Kun Ming male mice for 6 days, followed by injection of caerulein to induce AP. GW9662 (0.3 mg/kg), a specific peroxisome proliferator-activated receptor gamma (PPARγ) antagonist, was intravenously injected along with curcumin. Murine macrophage RAW264.7 cells were treated with 100 μmol/l curcumin for 2 h, and then stimulated with 0.1 μ g/ml lipopolysaccharide (LPS). Serum amylase and transaminase levels were measured at 10 h after AP. TNF-α level in mouse serum and cell culture medium were detected by ELISA. Expression of PPARγ and NF-κB were analyzed by RT-PCR and Western blot. Results: Curcumin significantly decreased the pancreas injury and reversed the elevation of serum amylase, ALT and AST activities and TNF-α level in mice with AP. Curcumin treatment inhibited the elevation of NF-κB-p65 in the nucleus of mouse pancreas AP group and RAW264.7 cells, but significantly increased the expression of PPARγ. GW9662 could abolish the effects of curcumin on serum levels of amylase, ALT, AST, TNF-α, and NF-κB level. Interpretation & conclusions: Our results suggest that curcumin could attenuate pancreas tissue and other organ injury by inhibiting the release of inflammatory cytokine TNF-α. These effects may involve upregulation of PPARγ and subsequent downregulation of NF-κB.

How to cite this article:
Yu WG, Xu G, Ren GJ, Xu X, Yuan HQ, Qi XL, Tian KL. Preventive action of curcumin in experimental acute pancreatitis in mouse.Indian J Med Res 2011;134:717-724

How to cite this URL:
Yu WG, Xu G, Ren GJ, Xu X, Yuan HQ, Qi XL, Tian KL. Preventive action of curcumin in experimental acute pancreatitis in mouse. Indian J Med Res [serial online] 2011 [cited 2020 Mar 31 ];134:717-724
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Full Text

Acute pancreatitis (AP) is a common cause of emergency hospital admission, with an increase in the incidence rate during the past 30 years [1],[2],[3],[4] . Studies have demonstrated that inflammatory cytokines play an important role in the induction and severity of AP [5]. Clinical and experimental studies have shown that serum tumour necrosis factor-α (TNF-α) and some interleukins (IL) are increased in patients with AP[6],[7],[8] . These inflammatory cytokines expressed by activated macrophages, locally increase the severity of AP [9]. A key regulator of cytokine induction is nuclear factor-κB (NF-κB), which is usually elevated in the pancreas during AP. Inhibition of NF-κB activation results in a decrease in the release of inflammatory cytokines [7] .

Curcumin, a yellow coloured phenolic pigment extracted from the rhizome of herb Curcuma longa, is widely reported to have potent anti-oxidative, anti-inflammatory and anti-carcinogenic effects. The anti-inflammatory action of curcumin seems to be closely related to inhibition of TNF-α and other inflammatory cytokines production and suppression of NF-κB activation by blocking phosphorylation of inhibitory factor I-kappa B kinase (IκB)[10],[11],[12] .

Peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated transcriptional factor, plays an important role in inflammation. Studies have demonstrated that ligand activation of PPARγ inhibits the activity of NF-κB, and negatively regulates inflammatory responses in vivo[13],[14]. A study demonstrated that curcumin can activate PPARγ and thus may be used as an agonist of PPARγ[15] . Therefore, the present study was focused on the preventive effect of curcumin in AP in mouse model and to investigate the possible mechanism of action.

 Material & Methods

Reagents: Curcumin, caerulein, PPARγ antagonist GW9662 and LPS were purchased from Sigma (USA). TRIzol reagent was purchased from Invitrogen (USA). The reverse transcription kit, Taq DNA polymerase, and PCR kit were purchased from Fermentas (USA). Rat anti-PPARγ, anti-NF-κB-p65, anti-β-actin and anti-lamin B antibodies were purchased from Santa Cruz Biotechnology (USA), and Goat anti-mouse IgG from GenScript Company (Nanjing). The EasyECL assay kit and nuclear protein extraction kit were purchased from Biomed Company, China. The BCA kit was purchased from Galen Company, Hongkong. The ELISA kit specific for rat TNF-α was from Wuhan Boster Biological Technology, Ltd., China. DMEM medum was purchased from Gibco, USA and foetal bovine serum was purchased from Biochrom (Germany).

Animals: Four-week old Kun Ming male mice, weighing 30±2 g, were purchased from the Experimental Animal Center of Shandong University School of Medicine, Shandong, PR China. The animals were housed 6 per cage under standardized conditions (25±3°C, 12 h light/dark cycle, humidity 50±10%) with free access to pelleted food and tap water. All experiments were conducted in the Department of Biochemistry and Molecular Biology, Shandong University School of Medicine with the approval of the Institutional Experimental Animal Care and Use Committee of Shandong University.

Animal treatment procedures: A total of 40 healthy Kun Ming male mice were randomly divided into four groups and were fasted for 12 h with free access to water. AP was induced by intraperitoneal injection of 50 μg/kg bodoy wt. (bw) caerulein (dissolved in normal saline) once per hour, repeated 7 times[16] . In the negative control group, caerulein was replaced by normal saline. In curcumin group, prior to caerulein injection, mice were intraperitoneally injected with 50 mg/kg bw curcumin (dissolved in 10% DMSO) [11] once a day for 6 consecutive days. To block PPARγ activity, a separate group of animals was treated with PPARγ antagonist, GW9662 (0.3 mg/kg bw) along with curcumin through intravenous injection prior to AP induction. Ten hours after AP induction [17] , the animals were killed and blood and tissue samples were collected.

Detection of serum amylase and transaminase activities: Blood was drawn from ophthalmic arteries, allowed to clot and centrifuged at 12000 g/min for 10 min. The serum was preserved at -80°C prior to analysis. The serum amylase, ALT and AST activities were analyzed by an automatic biochemical analyzer.

Pathological examination of mice pancreas: The mice were euthanized and pancreases were removed. The general morphologies of the pancreases were observed and recorded. Each pancreas was divided into two sections. One half was used to make paraffin-embedded sections, which were stained by hematoxylin and eosin (H & E) and pathologically examined. Schmidt criterion was employed for histopathological scoring in pathological evaluation [18] . The other half was subjected to RNA and protein extraction.

Curcumin treatment of murine macrophage RAW264.7 cells: Murine macrophage RAW264.7 cells (kindly provided by Prof. Chengjiang Gao from the Immunology Institute of Medical School of Shandong University) were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10 per cent foetal bovine serum, 50 units/ml penicillin and 50 μg/ml streptomycin at 37°C in a humidified CO2 incubator (5% CO2 , 95% air). RAW 264.7 cells were plated at a density of 6×105 /well in a 6-well plate. For all experiments, cells were grown to 80-90 per cent confluence. Cells were incubated in serum-free DMEM for 2 h and incubated with 100 μmol/l curcumin (dissolved in DMSO) at 37°C for another 2 h. After that, lipopolysaccharide (LPS) was added to achieve a final concentration of 0.1 μg/ml. Stimulation continued for 4 h, after which the supernatant was collected for TNF-α determination and cells were lysed for subsequent RNA or protein isolation. Triplicate samples were used for each treatment.

ELISA detection of TNF-α level: Enzyme-linked immunosorbent assays (ELISAs) were used to detect TNF-α level in mouse serum and the culture medium of RAW264.7 cells according to the manufacturer's instructions. All TNF-α determinations were performed in duplicate serial dilutions.

Reverse transcription-polymerase chain reaction (RT-PCR) for PPARγ mRNA expression in pancreases and RAW264.7 cells: Total RNAs in pancreases and RAW 264.7 cells were extracted with Trizol reagent according to the manufacturer's protocol and quantified by UV spectrophotometry. A total of 3 μg RNA was reverse transcribed into cDNA, and the resulting product was used as a template for PCR amplification of PPARγ genes. The PCR reaction system was set as 50 μl. β-actin was used as an internal reference under the same experimental conditions. Primers for PPARγ and β-actin were synthesized by Shanghai Sangon Biological Engineering Technology & Service Co., Ltd. Primers for PPARγ (477 bp) were: sense, 5'-CGTGATGGAAGACCACTCGC-3', antisense, 5'- AACCTGATGGCATTGTGAGA-3'; for β-actin (218 bp) were: sense, 5'-TGGTGGGAATGGGTCAGA-3', antisense, 5'-ACGGTTGGCCTTAGGGTT-3'. The cDNA was subjected to denaturation at 94°C for 2 min, followed by 32 cycles of 94°C for 30 sec, 56°C for 30 sec, and 72°C for 1 min, followed by a final extension step at 72°C for 10 min. PCR products were separated on 1 per cent agarose gel by electrophoresis, and the images were captured with the Gel Imaging System. Quantity One Software (? Source) was used to analyze the relative quantity of each band. The relative amount of PPARγ mRNA was normalized to β-actin.

Western blot analysis of NF-κB and PPARγ protein expression in pancreases and RAW264.7 cells: Total cellular and nuclear proteins in pancreas and RAW264.7cells were extracted and quantified with the BCA protein assay kit. Equal amounts of protein (50 μg) were separated by sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and then transferred to a polyvinylidine difluoride (PVDF) membrane. The membrane was blocked for 1 h in TBS buffer (20mM Tris-HCl, 150mM NaCl, pH7.5) containing 5 per cent defatted milk at room temperature. The membrane was then incubated with primary antibody (mouse antihuman NF-κB-p65, PPARγ, β-actin or lamin B antibody; diluted at 1:1000) at room temperature for 2 h and at 4°C overnight. After washing in TBS buffer, the membrane was incubated with a HRP-coupled secondary antibody diluted 1:2000 for 1 h. Membrane-bound horse radish peroxidase-labelled protein bands were detected with enhanced chemiluminescent reagents and chemiluminescent signals were detected using X-ray film. The relative amount of each band was analyzed with Quantity One software. The ratios of PPARγ:β-actin and nuclear NF-κB:lamin B were employed to express the relative amounts of both proteins.

Statistical analysis: The data were analyzed with SPSS 10.0 software (SPSS Co., II, USA). Inter-group comparisons were performed with one-way ANOVAs. P<0.05 was considered as statistically significant.


Pathological examination of mouse pancreas: Compared with the control group (histopathological scoring: 1.5±0.2, [Figure 1]A), the mouse pancreas in the AP group (histopathological scoring: 13.2±1.7, [Figure 1]B showed haemorrhage and exudation. The pancreatic acinuses were diffusely expanded, the pancreatic cells underwent necrosis, and the inter-lobular and perivascular regions were infiltrated with multiple leukocytes. The necrosis rate and inflammatory cell infiltration were significantly (P<0.05) decreased in the pancreas in the curcumin group (histopathological scoring: 6.9±0.8, [Figure 1]C) as compared to the AP group. {Figure 1}

Effect of curcumin on serum amylase and transaminase activities: Five hours after induction of AP, mice in the control group were still active, whereas mice in AP group were sick and reduced their physical activities. Ten hours after induction of AP, the serum amylase, ALT and AST activities of mice in the AP group were increased in comparison with those in the control group (P<0.01, [Table 1]). However, curcumin treatment significantly reversed the elevation of serum amylase, ALT and AST activities in AP mice (P<0.05, [Table 1]).{Table 1}

Effect of curcumin on the release of TNF-α: In the in vivo experiment, mouse serum TNF-α level increased in the AP group at 10 h after induction of AP (P<0.05) compared to control, whereas curcumin treatment significantly reduced the serum TNF-α level in AP mice (P<0.05) [Table 1]. TNF-α levels in the culture media of RAW264.7 cells were significantly elevated after LPS stimulation (P<0.05) compared to control which significantly reduced in the presence of curcumin (P<0.05).

Effect of curcumin on nuclear NF-κB expression: Western blotting revealed that expression of NF-κB-p65 was significantly (P<0.05) increased in the nucleus of pancreas in AP group compared to the control group. Curcumin treatment inhibited the elevation of NF-κB-p65 in AP mice [Figure 2]. After LPS stimulation, NF-κB expression was significantly increased (P <0.05) in RAW264.7 cells and considerably decreased in the presence of 100 μmol/l curcumin [Figure 3].{Figure 2}{Figure 3}

Effect of curcumin on PPARγ expression : PPARγ expression was reduced at both the mRNA and protein levels in the pancreas of AP group, and this effect was significantly (P<0.05) reversed by curcumin treatment [Figure 4] A and B. Similarly, after LPS (0.1 μg/ml) stimulation, PPARγ was decreased at both the mRNA and protein levels in RAW264.7 cells and was significantly (P<0.05) increased compared to control at both levels in the presence of 100 μmol/l curcumin [Figure 5] A and B.{Figure 4}{Figure 5}

Effect of the PPARγ antagonist GW9662: GW9662 partially counteracted the effects of curcumin on serum amylase, ALT, AST and TNF-α in AP mice [Table 1]. A Western blot analysis of NF-κB expression showed that curcumin-mediated downregulation of nuclear NF-κB-p65 protein was significantly (P <0.05) suppressed by GW9662 [Figure 6].{Figure 6}


Curcumin has been shown to suppress multiple signaling pathways by interacting with a wide variety of proteins and modify their expression and activity, including inflammatory cytokines and enzymes, transcription factors, and gene products linked with cell survival, proliferation, invasion, and angiogenesis [19] . The aim of the present study was to investigate the potential preventive effect of curcumin to AP generation by using caerulein-induced pancreatitis in mouse model. Our results demonstrated that intraperitoneal injection of caerulein caused necrosis and haemorrhage and neutrophils infiltration in the mouse pancreas in AP group. Serum amylase and transaminase activities and TNF-α levels were all significantly elevated in the AP group. Curcumin treatment significantly decreased the histopathological score and reversed the elevation of serum amylase, ALT and AST activities and TNF-α levels. Pancreatic cell injury and enzyme release induce activation of pro-inflammatory cells, thereby resulting in the production of a large number of inflammatory mediators, which cause a systemic inflammatory response and multiple organ injury [20],[21] . Our results showed that curcumin not only attenuated pancreatic tissue injury, but also attenuated other organ injury by inhibiting the release of inflammatory cytokine TNF-α. Consistent with the in vivo experiment, TNF-α levels in the culture media of RAW264.7 cells were significantly elevated after LPS stimulation, while being significantly reduced in the presence of curcumin. Previous studies showed that curcumin has profound effects on modulation of TNF-induced signaling, as well as inhibition of expression of TNF. Curcumin treatment inhibited LPS or phorbol methyl acetate (PMA)-induced TNF-α levels in dendritic cells, macrophages, monocytes alveolar macrophages, and endothelial and bone marrow cells [19] . Curcumin inhibited the expression of TNF mRNA in the livers of copper uploaded rats and CCl 4 -induced hepatic fibrosis [22] . Our results were in agreement with Gukovsky et al[11] who demonstrated that curcumin prominently reduced tissue injury as well as cytokine damage in both cerulein- and ethanol-induced pancreatitis, and curcumin's inhibitory effect on inflammatory mediators resulted in improvement in disease severity as measured by histology, serum amylase, pancreatic trypsin, and neutrophil infiltration. Gulcubuk et al[23] demonstrated that curcumin failed in the reduction of tissue injury, and suggested that the failure might have been associated with the type of the experimental model used and the observation period and the level of cytokine.

The mechanism by which curcumin induces its anti-inflammatory effects is yet to be elucidated. Activation of transcription factor NF-κB, a key regulator of inflammatory molecule expression, is an early event in experimental pancreatitis and correlates with the inflammatory response. The present study revealed that expression of NF-κB-p65 was significantly increased in the nucleus of mouse pancreas in AP group and curcumin treatment inhibited the elevation of NF-κB-p65. After LPS stimulation, NF-κB expression was significantly increased in RAW264.7 cells and considerably decreased in the presence of curcumin. Samuhasaneeto et al[24] suggested that curcumin treatment improved liver histopathology in early stage of ethanol-induced liver injury by reduction of oxidative stress and inhibition of NF-κB activation. Gukovsky et al [11] reported that curcumin decreased inflammation by markedly decreasing activation of NF-κB and activator protein-1 (AP-1) as well as inhibiting mRNA induction of IL-6, TNF-α, and inducible nitric oxide synthetase (iNOS) in the pancreas in two rat models of experimentally-induced pancreatitis, assessed by DNA binding and degradation of inhibitory I-κB proteins. They indicated that blocking key signals of the inflammatory response ameliorates pancreatitis in both ethanol and nonethanol models [8]. Under normal physiological circumstances, inactivated NF-κB is sequestered by the inhibitor I-κB in the cytoplasm. When cells are stimulated by inflammatory factors, I-κB is phosphorylated and degradated through the ubiquitin-proteasome system. Then NF-κB is activated and translocates to the nucleus to initiate transcription of TNF-α and multiple pro-inflammatory factors[25]. Curcumin completely blocks TNF-induced NF-κB activation through the inhibition of phosphorylation of NF-κB, leading to suppression of cell survival, proliferative and inflammatory gene products[26]. Other studies showed that curcumin inhibited TNF-induced NF-κB activation by inhibiting proteasomal activities instead of IκBα kinase (IKK) activation in MCF-7 cells [27]. Our results indicated that elevation and activation of NF-κB might be a key process in the pathogenesis of AP, and that inhibition of NF-κB by curcumin should be explored as a preventive and therapeutic means of AP control and treatment.

Previous studies reported that curcumin significantly inhibited cell proliferation, induced apoptosis, inhibited of hepatic stellate cells (HSC) activation and suppressed hepatic fibrogenesis, attenuated STZ-induced memory deficits, eliminated ox-LDL stimulated HSC activation by stimulating PPAR-γ activity. Blocking the trans-activity by PPAR-γ antagonist significantly decreased these effects of curcumin[26],[28],[29],[30],[31] . Studies performed by Jacob et al[32] suggested that the anti-inflammatory effect of curcumin is mediated by the upregulation of PPAR-γ activation. Combined usage of GW9662 significantly impaired the function of curcumin in an experimental model of sepsis[33]. The present study showed that PPARγ expression was reduced at both the mRNA and protein levels in AP group mouse pancreas and in LPS-stimulated RAW264.7 cells, and curcumin treatment significantly increased the expression of PPARγ. Activation of PPAR-γ suppressed inflammatory responses by inhibiting the release of IL-1β, IL-6, TNF-α and expression of NF-κB and the adhesion molecule ICAM-1[34],[35] . Concurrent administration of curcumin and GW9662 in the mouse with acute pancretitis abolished the effects of curcumin on serum levels of amylase, the liver enzymes ALT and AST, and TNF-α. A Western blot analysis of NF-κB expression showed that curcumin-mediated downregulation of nuclear NF-κB-p65 protein was significantly suppressed by GW9662, which suggests that downregulation of NF-κB by curcumin is mediated through PPAR-γ. Investigation conducted by Ghosh et al [36] in Sprague-Dawley rats with chronic renal failure suggested that curcumin in a dose dependent manner antagonized the TNF-α-mediated decrease in PPAR-γ and blocked transactivation of NF-κB and repression of PPARγ. Collectively, these results suggest that the preventive effects of curcumin against AP were associated with PPAR-γ upregulation and subsequent NF-κB downregulation, indicating an important role of curcumin as a PPAR-γ agonist.

In summary, this study showed that curcumin induced anti-inflammatory effects caused by the upregulation of PPAR-γ were associated with the NF-κB pathway. Future studies are warranted to confirm this conclusion.

Competing interests : The authors declare that they have no competing interests.


This work was supported by The Science Development Project of Shandong Province (2006GG2202021), China.


1Omdal T, Dale J, Lie SA, Iversen KB, Flaatten H, Ovrebo K. Time trends in incidence, etiology, and case fatality rate of the first attack of acute pancreatitis. Scand J Gastroenterol 2011; 46 : 1389-98.
2Sandzén B, Rosenmüller M, Haapamki MM, Nilsson E, Stenlund HC, Oman M. First attack of acute pancreatitis in Sweden 1988 - 2003: incidence, aetiological classification, procedures and mortality - a register study. BMC Gastroenterol 2009; 9 : 18.
3Yadav D, Lowenfels AB. Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review. Pancreas 2006; 33 : 323-30.
4Spanier BW, Dijkgraaf MG, Bruno MJ. Epidemiology, aetiology and outcome of acute and chronic pancreatitis: An update. Best Pract Res Clin Gastroenterol 2008; 22 : 45-63.
5Czako L, Takacs T, Varga IS, Hai DQ, Tiszlavicz L, Hegyi P, et al. The pathogenesis of L-arginine-induced acute necrotizing pancreatitis: inflammatory mediators and endogenous cholecystokinin. J Physiol Paris 2000; 94 : 43-50.
6Chen CC, Wang SS, Lee FY, Chang FY, Lee SD. Proinflammatory cytokines in early assessment of the prognosis of acute pancreatitis. Am J Gastroenterol 1999; 94 : 213-8.
7Kim H, Seo JY, Roh KH, Lim JW, Kim KH. Suppression of NF-kappaB activation and cytokine production by N-acetylcysteine in pancreatic acinar cells. Free Radic Biol Med 2000; 29 : 674-83.
8Osman MO, Gesser B, Mortensen JT, Matsushima K, Jensen SL, Larsen CG. Profiles of pro-inflammatory cytokines in the serum of rabbits after experimentally induced acute pancreatitis. Cytokine 2002; 17 : 53-9.
9Shifrin AL, Chirmule N, Zhang Y, Raper SE. Macrophage ablation attenuates adenoviral vector-induced pancreatitis. Surgery 2005; 137 : 545-51.
10Abe Y, Hashimoto S, Horie T. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res 1999; 39 : 41-7.
11Gukovsky I, Reyes CN, Vaquero EC, Gukovskaya AS, Pandol SJ. Curcumin ameliorates ethanol and nonethanol experimental pancreatitis. Am J Physiol Gastrointest Liver Physiol 2003; 284 : G85-95.
12Kim HY, Park EJ, Joe EH, Jou I. Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation of Src homology 2 domain-containing tyrosine phosphatase 2 in brain microglia. J Immunol 2003; 171 : 6072-9.
13Chen F, Wang M, O'Connor JP, He M, Tripathi T, Harrison LE. Phosphorylation of PPARgamma via active ERK1/2 leads to its physical association with p65 and inhibition of NF-kappabeta. J Cell Biochem 2003; 90 : 732-44.
14Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaâ-regulated gene products. Cancer Res 2007; 67 : 3853-61.
15Xu J, Fu Y, Chen A. Activation of peroxisome proliferator-activated receptor-gamma contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth. Am J Physiol Gastrointest Liver Physiol 2003; 285 : G20-30.
16Niederau C, Ferrell LD, Grendell JH. Caerulein-induced acute necrotizing pancreatitis in mice: Protective effects of proglumide, benzotript, and secretin. Gastroenterology 1985; 88 : 1192-204.
17Shimizu T, Shiratori K, Sawada T, Kobayashi M, Hayashi N, Saotome H, et al. Recombinant human interleukin-11 decreases severity of acute necrotizing pancreatitis in mice. Pancreas 2000; 21 : 134-40.
18Schmidt J, Lewandrowsi K, Warshaw AL, Compton CC, Rattner DW. Morphometric characteristics and homogeneity of a new model of acute pancreatitis in the rat. Int J Pancreatol 1992; 12 : 41-51.
19Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation,invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett 2008; 269 : 199-225.
20Raraty MG, Connor S, Criddle DN, Sutton R, Neoptolemos JP. Acute pancreatitis and organ failure: pathophysiology, natural history, and management strategies. Curr Gastroenterol Rep 2004; 6 : 99-103.
21Gómez-Cambronero LG, Sabater L, Pereda J, Cassinello N, Camps B, Viña J, et al. Role of cytokines and oxidative stress in the pathophysiology of acute pancreatitis: therapeutical implications. Curr Drug Targets Inflamm Allergy 2002; 1 : 393-403.
22Fu Y, Zheng S, Lin J, Ryerse J, Chen A. Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation. Mol Pharmacol 2008; 73 : 399-409.
23Gulcubuk A, Altunatmaz K, Sonmez K, Haktanir-Yatkin D, Uzun H, Gurel A, et al. Effects of curcumin on tumour necrosis factor-alpha and interleukin-6 in the late phase of experimental acute pancreatitis. J Vet Med A Physiol Pathol Clin Med 2006; 53 : 49-54.
24Samuhasaneeto S, Thong-Ngam D, Kulaputana O, Suyasunanont D, Klaikeaw N. Curcumin decreased oxidative stress, inhibited NF-kappaB activation, and improved liver pathology in ethanol-induced liver injury in rats. J Biomed Biotechnol 2009; 2009 : 981963.
25Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev 2004; 18 : 2195-224.
26Aggarwal BB, Bhatt ID, Ichikawa H, Ahn KS, Sethi G, Sandur SK, et al. Curcumin: Biological and medicinal properties. In: Ravindran PN, Nirmal Babu K, Shivaraman, editors. Turmeric: the genus Curcuma. Boca Raton, FL: The CRC Press; 2006. p. 297-368.
27Yoon H, Liu RH. Effect of selected phytochemicals and apple extracts on NF-kappaB activation in human breast cancer MCF-7 cells. J Agric Food Chem 2007; 55 : 3167-73.
28Aggarwal BB, Surh YJ, Shishodia S. The molecular targets and therapeutic uses of curcumin in health and disease. Adv Exp Med Biol 2007; 595 : 1-512.
29Lin J, Chen A. Activation of peroxisome proliferator-activated receptor-gamma by curcumin blocks the signaling pathways for PDGF and EGF in hepatic stellate cells. Lab Invest 2008; 88 : 529-40.
30Rinwa P, Kaur B, Jaggi AS, Singh N. Involvement of PPAR-gamma in curcumin-mediated beneficial effects in experimental dementia. Naunyn Schmiedebergs Arch Pharmacol 2010; 381 : 529-39.
31Kang Q, Chen A. Curcumin eliminates oxidized LDL roles in activating hepatic stellate cells by suppressing gene expression of lectin-like oxidized LDL receptor-1. Lab Invest 2009; 89 : 1275-90.
32Jacob A, Wu R, Zhou M, Wang P. Mechanism of the anti-inflammatory effect of curcumin: PPAR-ã activation. PPAR Res 2007; 2007 : 89369.
33Siddiqui AM, Cui X, Wu R, Dong W, Zhou M, Hu M, et al. The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by up-regulation of peroxisome proliferator-activated receptor-gamma. Crit Care Med 2006; 34 : 1874-82.
34Su CG, Wen X, Bailey ST, Jiang W, Rangwala SM, Keilbaugh SA, et al. A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response. J Clin Invest 1999; 104 : 383-9.
35Chinetti G, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors and inflammation: from basic science to clinical applications. Int J Obes Relat Metab Disord 2003; 27 (Suppl 3): S41-5.
36Ghosh SS, Massey HD, Krieg R, Fazelbhoy ZA, Ghosh S, Sica DA, et al. Curcumin ameliorates renal failure in 5/6 nephrectomized rats: role of inflammation. Am J Physiol Renal Physiol 2009; 296 : F1146-57.