curcumin and Pancreatitis

We aimed to investigate whether nano-curcumin as an anti-inflammatory agent is effective in patients with mild and moderate AP. This study was a double-blind, parallel-arm randomized controlled trial conducted at Taleghani hospital, Tehran, Iran. Eligible subjects with a diagnosis of mild and moderate AP were randomly assigned to receive either two doses of nano-curcumin (40 mg) or placebo (control) daily for 2 weeks. The primary endpoint was gastrointestinal (GI) ward length of stay (LOS). A total of 42 patients were randomly assigned to receive either nano-curcumin (n = 21) or placebo (n = 21). Compared with placebo, nano-curcumin supplementation decreased hospital LOS (RR = 0.67, 95% CI: 0.502-0.894; p = 0.006), reduced the need for analgesics over time (OR = 0.576, 95% CI: 0.421-0.790; p = 0.001), and increased overall appetite score over the study period (β = 0.104, SE: 0.053; p = 0.049). No adverse effects or mortality were reported and there was no withdrawal during the study period. The results indicate that nano-curcumin as an adjuvant therapy is safe and may reduce GI ward LOS, analgesics requirement, and improve the overall appetite in patients with mild and moderate AP. Future multi-center trials with larger sample sizes are required to verify these findings. Clinical trial registration: www.ClinicalTrials.gov NCT04989166.

Topics: Acute Disease; Analgesics; Curcumin; Dietary Supplements; Double-Blind Method; Humans; Iran; Pancreatitis

Oxidative stress occurs in association with painful exacerbations of chronic pancreatitis and antioxidant supplementation appears to benefit this condition. Curcumin, the active constituent of turmeric, is known to exhibit antioxidant activity. This pilot study was therefore undertaken to evaluate the effect of oral curcumin with piperine on the pain, and the markers of oxidative stress in patients with tropical pancreatitis (TP).. Twenty consecutive patients with tropical pancreatitis were randomised to receive 500 mg of curcumin with 5 mg of piperine, or placebo for 6 wk, and the effects on the pattern of pain, and on red blood cell levels of malonyldialdehyde (MDA) and glutathione (GSH) were assessed.. There was a significant reduction in the erythrocyte MDA levels following curcumin therapy compared with placebo; with a significant increase in GSH levels. There was no corresponding improvement in pain.. Oral curcumin with piperine reversed lipid peroxidation in patients with tropical pancreatitis. Further studies with large sample are needed to define its effect on the pain and other manifestations of tropical pancreatitis.

Topics: Adolescent; Adult; Aged; Antioxidants; Curcumin; Female; Humans; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Pancreatitis; Pilot Projects; Single-Blind Method

Acute pancreatitis (AP) is a pathology characterized by activated digestive enzymes to digest pancreatic tissue and inflammation. This study aimed to investigate the effect of curcumin, which has antioxidant and anti-inflammatory properties, on AP and its effectiveness at different doses.. Forty Sprague Dawley albino male rats, 12 weeks old, weighing 285-320 g, were used in the study. The rats were divided into control, curcumin, AP, low (100 mg/kg), and high (200mg/kg) dose curcumin groups. An experimental pancreatitis model was created with 5 g/kg L-arginine and samples (amylase, lipase, IL-1β, IL-6, TNF-alpha, CRP, histopathological) were taken after 72 hours.. There was no difference between the groups in terms of the weight of the rats (p=0.76). In the AP group, it was observed that the experimental pancreatitis model was successfully created after examination. Laboratory and histopathological examination results in the curcumin-administered groups were regressed compared to the AP group. The decrease in laboratory values was higher in the high-dose curcumin group than in the low-dose (p<0.001).. Laboratory and histopathological changes occur in AP according to clinical severity. The antioxidant and anti-inflammatory effects of curcumin are known. In the light of this information and according to the results of our study, it has been shown that curcumin is effective in the treatment of AP, and the effect of curcumin increases with the dose increase. Curcumin is effective in treating AP. However, while high-dose curcumin was more effective in inflammatory response than low-dose, it showed similar histopathological results.. Acute, Curcumin, Cytokines, Inflammation, Pancreatitis.. La pancreatite acuta (AP) è una patologia caratterizzata dall’attivazione di enzimi digestivi pancreatici in grado di determinare la digestione del tessuto pancreatico e l’infiammazione. Questo studio era finalizzato a studiare l’effetto della curcumina, che ha proprietà antiossidanti e antinfiammatorie, sull’AP e la sua efficacia a diverse dosi. Nello studio sperimentale sono stati utilizzati quaranta ratti maschi albini Sprague Dawley, di 12 settimane di età, del peso di 285-320 g. I ratti sono stati divisi in cinque gruppi: 1) di controllo; 2) trattati con curcumina; 3) grupp AP (pancreatite acuta) provocata sperimentalmente; 4) AP, trattata con curcumina a basso dosaggio (100 mg/kg); 5) AP trattata con curcumina ad alto dosaggio (200 mg/kg). È stato creato un modello sperimentale di pancreatite con 5 g/kg di L-arginina e sono stati prelevati campioni (amilasi, lipasi, IL-1β, IL- 6, TNF-alfa, CRP, istopatologico) dopo 72 ore. RISULTATI: Non c’era differenza tra i gruppi in termini di peso dei ratti (p=0,76). Nel gruppo 3 (AP), è stato osservato dopo l’esame che il modello sperimentale di pancreatite era stato creato con successo. I risultati degli esami di laboratorio e istopatologici nei gruppi trattati con curcumina sono risultati regrediti rispetto a quelli del gruppo AP. La diminuzione dei valori di laboratorio è stata maggiore nel gruppo trattato con curcumina ad alto dosaggio rispetto a quello a basso dosaggio (p<0,001). CONCLUSIONE: Cmbiamenti dei dati di laboratorio e quelli istopatologici si verificano in AP in base alla gravità clinica. Sono noti gli effetti antiossidanti e antinfiammatori della curcumina. Alla luce di queste informazioni e in base ai risultati del nostro studio, è stato dimostrato che la curcumina è efficace nel trattamento dell’AP e l’effetto della curcumina aumenta con l’aumento della dose. La curcumina è efficace nel trattamento dell’AP. Tuttavia, sebbene la curcumina ad alte dosi fosse più efficace nella risposta infiammatoria rispetto a quelle a basse dosi, ha mostrato risultati istopatologici simili.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Antioxidants; Arginine; Curcumin; Disease Models, Animal; Inflammation; Pancreas; Pancreatitis; Rats; Rats, Sprague-Dawley

Curcumin was used to interfere with acute pancreatitis model rats to explore its possible mechanism. One hundred and twenty rats were randomly divided into blank group, model group, model+curcumin group, model+mock+curcumin group, model+antagonist+curcumin group and model+curcumin+LY294002 group, with 20 rats in each group. The wet/dry weight ratio of pancreatic tissue was measured and the pathological changes of pancreas were observed by HE staining. The apoptosis was detected by TUNEL staining; the levels of serum amylase, lipase, Bcl-2 and Bax were detected by ELISA, and the levels of PI3 K, Akt and p-Akt in pancreatic tissue were measured by Western blot. HE staining showed that curcumin could improve the pathological changes of pancreas and reduce the pathological score of pancreas, while ELISA results showed that curcumin could decrease the levels of amylase, lipase and Bax in peripheral serum and increase the concentration of Bcl-2. Western blot results showed that the expression levels of PI3 K and p-Akt in pancreatic tissue of model rats were up-regulated after the intervention of curcumin, and the apoptosis rate of pancreatic cells decreased in TUNEL staining. The above effects could be weakened by miR-198 antagonist and PI3 K-Akt signal pathway inhibitor LY294002. In conclusion, curcumin has an ideal effect on acute pancreatitis, and its mechanism may be mediated by miR-198-PI3 K-Akt axis.

Topics: Acute Disease; Animals; Apoptosis; Curcumin; MicroRNAs; Pancreatitis; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction

Curcumin has been demonstrated to reduce markers of inflammation during acute pancreatitis (AP). However, the underlying mechanisms of the protective effects of curcumin are unknown. In the present study the effects of curcumin in an AP animal model and cell models was examined and the underlying mechanisms were investigated. An AP animal model was established by injection of 5% sodium taurocholate into the biliopancreatic duct of rats, and the cell model was established by treatment with 0.5 nM cerulein with an optimal concentration of lipopolysaccharide in AR42J rat pancreatic cancer cells. Amylase activity and arterial blood gas composition were assessed by automatic biochemical and blood gas analyzers. Pathological alteration of the pancreas was determined by hematoxylin and eosin staining. Interleukin (IL‑6), tumor necrosis factor (TNF)‑α and C‑reactive protein (CRP) levels were measured by ELISA. Cell viability was determined by Cell Counting Kit‑8 and protein expression levels were assessed by western blotting. Curcumin reduced the ascites volume after 12 and 24 h, the weight of pancreas after 12, 24 and 36 h of surgery, but also attenuated injury to the pancreas. Serum expression levels of TNF‑α and CRP were reduced by curcumin. In addition, curcumin decreased the cell viability, amylase activity and the phosphorylation of p38 in AR42J cells, but did not affect the intracellular levels of IL‑6 and TNF‑α. Curcumin may lower the severity and inflammatory response via the mitogen‑activated protein kinase‑signaling pathway, to some extent. However, future studies are required to fully understand the protective effects of curcumin on AP.

Topics: Animals; C-Reactive Protein; Cell Line, Tumor; Curcumin; Disease Models, Animal; Female; Interleukin-6; MAP Kinase Signaling System; Pancreas; Pancreatitis; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Acute pancreatitis (AP) is a life-threatening condition. Using antioxidants in AP is insufficient and conflicting. Therefore, this study compared the effect of hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS), leptin or curcumin pretreatment on AP induced by L-arginine.. Forty adult male rats were used and classified into: 1) control; 2) AP group [each rat was intraperitoneally (i.p.) injected with 2 doses of L-arginine of 250 mg/100 g body weight (b.w.) with an interval of 1 h]; 3) NaHS+AP group (each rat was i.p. injected with 10 mg/kg b.w. of NaHS 1 h before induction of AP); 4) leptin+AP group (each rat was pretreated with 10 μg/kg b.w. of leptin 30 min before induction of AP; and 5) curcumin+AP group (in which rats were i.p. injected with 150 mg/kg b.w. of curcumin 30 min before induction of AP). Serum amylase, lipase, nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and corticosterone (CORT) levels were assayed. In addition, pancreatic tissues were obtained for histopathological examination and malondialde-hyde (MDA), total antioxidant capacity (TAC), and inducible nitric oxide synthase (iNOS) levels were measured.. All AP treated groups showed significant decrease in serum levels of pancreatic enzymes, NO, and TNF-α, and pancreatic MDA and iNOS levels, while TAC levels were significantly increased. NaHS caused more limitation of inflammation than leptin and curcumin by affecting iNOS. Leptin was more potent than curcumin due to the stimulatory effect of leptin on glucocorticoid release to counteract inflammation.. NaHS was more effective in AP amelioration than the leptin and curcumin.

Topics: Animals; Arginine; Corticosterone; Curcumin; Cytoprotection; Leptin; Male; Nitric Oxide Synthase Type II; Pancreas; Pancreatitis; Protective Agents; Rats; Rats, Wistar; Signal Transduction; Sulfides

BACKGROUND Inflammation plays an important role in initiation and development of severe acute pancreatitis (SAP). Curcumin exerts potent anti-inflammatory effects in many diseases, including acute pancreatitis. However, the specific molecular mechanisms are not clear. MATERIAL AND METHODS Intra-biliopancreatic duct injection of taurocholate was used to establish an animal model of SAP. Curcumin was administrated to animals as pre-treatments. Concentrations of cytokines in serum and ascites were measured by enzyme-linked immunosorbent assay (ELISA). A colorimetric method was used to determine the amylase activity. Western blotting was used to examine the expression levels and phosphorylation levels of proteins. Immunoprecipitation was used to assess the molecular association between apoptosis signal- regulating kinase 1 (ASK1) and thioredoxin (Trx). RESULTS Pre-treatment with curcumin reduced the concentrations of interleukin (IL6) and tumor necrosis factor (TNFα) in serum and ascites, as well as the ascites volume and amylase activity in SAP rats. Pre-treatment with curcumin reduced the expression level of TNF receptor-associated factor 1 (TRAF1), IL6, and TNFa in pancreas in SAP rats. Moreover, the phosphorylation levels of mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), MKK7, and c-Jun NH(2)-terminal protein kinase (JNK) were reduced by curcumin pre-treatment. The molecular association between ASK1 and Trx was recovered by curcumin pre-treatment. As a result, the nuclear translocation of nuclear factor kappa B (NF-κB) was suppressed in pancreases from SAP rats. CONCLUSIONS Activation of the TRAF1/ASK1/JNK/NF-κB signaling pathway is involved in the inflammation of SAP. Curcumin exerts anti-inflammatory effects by suppressing this proinflammatory pathway.

Topics: Acute Disease; Amylases; Animals; Ascites; Curcumin; Cytokines; Disease Models, Animal; Male; MAP Kinase Kinase 4; MAP Kinase Kinase Kinase 5; NF-kappa B; Pancreatitis; Rats; Rats, Sprague-Dawley; Signal Transduction; Taurocholic Acid; Thioredoxins; TNF Receptor-Associated Factor 1

Increasing the intestinal dissolution of orally administered poorly water-soluble drugs that have poor oral bioavailability to a therapeutically effective level has long been an elusive goal. In this work, an approach that can greatly enhance the oral bioavailability of a poorly water-soluble drug such as curcumin (CUR) is developed, using a "Transformers"-like nanocarrier system (TLNS) that can self-emulsify the drug molecules in the intestinal lumen to form nanoemulsions. Owing to its known anti-inflammation activity, the use of CUR in treating pancreatitis is evaluated herein. Structural changes of the TLNS in the intestinal environment to form the CUR-laden nanoemulsions are confirmed in vitro. The therapeutic efficacy of this TLNS is evaluated in rats with experimentally induced acute pancreatitis (AP). Notably, the CUR-laden nanoemulsions that are obtained using the proposed TLNS can passively target intestinal M cells, in which they are transcytosed and then transported into the pancreatic tissues via the intestinal lymphatic system. The pancreases in rats that are treated with the TLNS yield approximately 12 times stronger CUR signals than their counterparts receiving free CUR, potentially improving the recovery of AP. These findings demonstrate that the proposed TLNS can markedly increase the intestinal drug dissolution, making oral delivery a favorable noninvasive means of administering poorly water-soluble drugs.

Topics: Acute Disease; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Curcumin; Drug Carriers; Drug Liberation; Emulsions; Humans; Intestinal Absorption; Nanostructures; Pancreatitis; Rats, Wistar; Solubility; Water

Acute pancreatitis (AP) is a serious inflammatory disorder of the pancreas with considerable mortality. The clinical therapy is hampered due to lack of any approved drug for AP. In this study, we developed curcumin (cur)-loaded poly (lactic-co-glycolic acid) cur microparticles (CuMPs) for sustained release. CuMPs were prepared by emulsion solvent evaporation method and characterized for shape, size, compatibility, and entrapment efficiency. The in vitro drug release and in vivo pharmacokinetic studies confirmed sustained release pattern of cur from CuMPs. The pharmacodynamic study was conducted in cerulein induced AP model. Prophylactic treatment was planned with single dose of CuMPs (equivalent to 7.5 mg/kg of cur) and compared with free cur given orally (100 mg/kg) and intraperitoneally (7.5 mg/kg) daily for 7 days. Interestingly, the effects of CuMPs were superior compared to the free drug administered either orally or intraperitoneally through repeated administrations. CuMPs showed significant decrease of serum amylase and lipase levels, oxidative and nitrosative stress was also significantly decreased. Moreover, CuMPs impressively decreased inflammatory cytokines. Our results may pave a way to propose similar strategy for many of promising natural products to combat several oxidative stress-mediated disorders via sustained release microparticle approaches.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Ceruletide; Curcumin; Cytokines; Delayed-Action Preparations; Drug Liberation; Male; Mice; Oxidative Stress; Pancreas; Pancreatitis; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Sprague-Dawley

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.. 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.. 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.. 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.

Topics: Alanine Transaminase; Amylases; Anilides; Animals; Cell Nucleus; Ceruletide; Curcuma; Curcumin; Disease Models, Animal; Gene Expression Regulation; Inflammation; Lipopolysaccharides; Macrophages; Male; Mice; NF-kappa B; Pancreatitis; Plant Extracts; PPAR gamma; Transaminases; Tumor Necrosis Factor-alpha

Curcuma longa (CL) has been reported to possess a variety of pharmacological activities. However, the effects of CL on acute pancreatitis (AP) have not yet been determined. To this end, we examined the effects of CL on cerulein-induced AP. Cell viability and cytokine productions were measured in pancreatic acini. Mice were divided into 3 groups: i) Normal group, ii) normal saline-treated group, iii) group treated with CL at a dose of 0.05, 0.1, 0.5 and 1 g/kg. CL was administered orally to mice for 7 days. The mice were intraperitoneally injected with the stable cholecystokinin analogue, cerulein (50 μg/kg), every hour for a total of 6 h. The mice were sacrificed 6 h after the completion of the cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphological examination, measurement of tissue myeloperoxidase activity, as well as the level of cytokines and heme oxygenase-1 (HO-1). The CL treatment reduced cerulein-induced cell death and cytokine production in pancreatic acini. The administration of CL significantly ameliorated the severity of pancreatitis and pancreatitis-associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization, necrosis, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as interleukin (IL)-1ß and -6 and tumor necrosis factor (TNF)-α. In order to identify the regulatory mechanism of CL on cerulein-induced pancreatitis, we examined the level of HO-1 in the pancreas. We found that the administration of CL induced HO-1. Our results suggest that CL plays a protective role in the development of AP and pancreatitis-associated lung injury.

Topics: Acute Disease; Animals; Ceruletide; Curcuma; Cytokines; Female; Heme Oxygenase-1; Lung Injury; Mice; Mice, Inbred C57BL; Pancreas; Pancreatitis; Peroxidase; Plant Extracts