The protective effect of nano-curcumin in experimental model of acute pancreatitis: The involvement of TLR4/NF-kB pathway

Document Type : Research Paper

Authors

1 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

3 Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Objective(s): The objective of the present study is to explore whether Nanocurcumin improves pancreatic inflammation through the inhibition of the TLR4/NFkB signaling pathway in cerulein-induced acute pancreatitis.
Methods: Acute pancreatitis was induced by five intraperitoneal (i.p.) injection of cerulein (50 μg/kg) with 1h intervals. Vehicle and nanocurcumin (100mg/kg/day) were given to the animals by oral gavage six days before the induction of pancreatitis. The last dose was administered 1 hour before pancreatitis induction. The serum level of amylase and lipase and the tissue level of MPO enzymes were assessed by biochemical analysis. Microscopic lesions were examined. In addition, the expression level of TLR4, NF-kB p65 and TNF-α proteins were measured by western blotting analysis.
Results: Nanocurcumin reduced the microscopic lesions. In addition, the drug decreased the level of amylase, lipase and MPO enzymes. Furthermore, nanocurcumin inhibited the cerulein-induced expression of TLR4, NF-kB p65 and TNF-α proteins.  
Conclusion: It is suggested that the anti-inflammatory effect of nanocurcumin on cerulein-induced acute pancreatitis may involve the inhibition of the TLR4/NFkB signaling pathway.

Keywords


1. Pandol SJ, Saluja AK, Imrie CW, Banks PA. Acute pancreatitis: bench to the bedside. Gastroenterology. 2007; 133(3): 1056.
2. Singh P, Garg PK. Pathophysiological mechanisms in acute pancreatitis: Current understanding. Indian J Gastroenterol. 2016; 35(3): 153-166.
3. Huang H, Liu Y, Daniluk J, Gaiser S, Chu J, Wang H, Li ZS, Logsdon CD, Ji B. Activation of nuclear factor-κB in acinar cells increases the severity of pancreatitis in mice. Gastroenterology. 2013; 144(1): 202-210.
4. Bhatia M, Wong FL, Cao Y, Lau HY, Huang J, Puneet P, Chevali L. Pathophysiology of acute pancreatitis. Pancreatology. 2005; 5(2-3): 132-144.
5. Watanabe T, Kudo M, Strober W. Immunopathogenesis of pancreatitis. Mucosal Immunol. 2017; 10(2): 283-298.
6. Vaz J, Akbarshahi H, Andersson R. Controversial role of toll-like receptors in acute pancreatitis. World J Gastroenterol. 2013; 19(5): 616-630.
7. Li Y, Zhou ZG, Xia QJ, Zhang J, Li HG, Cao GQ, Wang R, Lu YL, Hu TZ. Toll-like receptor 4 detected in exocrine pancreas and the change of expression in cerulein-induced pancreatitis. Pancreas. 2005; 30(4): 375-381.
8. Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci. 2009; 30(2): 85-94.
9. Rahimi HR, Mohammadpour AH, Dastani M, Jaafari MR, Abnous K, Ghayour Mobarhan M, Kazemi Oskuee R. The effect of nano-curcumin on HbA1c, fasting blood glucose, and lipid profile in diabetic subjects: a randomized clinical trial. Avicenna J Phytomed. 2016; 6(5): 567-577.
10. Mazzon E, Genovese T, Di Paola R, Muià C, Crisafulli C, Malleo G, Esposito E, Meli R, Sessa E, Cuzzocrea S. Effects of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, in a mouse model of acute pancreatitis induced by cerulein. Eur J Pharmacol. 2006; 549(1-3): 149-156.
11. Zhong K. Curcumin Mediates a Protective Effect Via TLR-4/NF-κB Signaling Pathway in Rat Model of Severe Acute Pancreatitis. Cell Biochem Biophys. 2015; 73(1): 175-180.
12. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol. 1982; 78(3): 206-209.
13. Dembiński A, Warzecha Z, Ceranowicz P, Warzecha AM, Pawlik WW, Dembiński M, Rembiasz K, Sendur P, Kuśnierz-Cabala B, Tomaszewska R, Chowaniec E, Konturek PC. Dual, time-dependent deleterious and protective effect of anandamide on the course of cerulein-induced acute pancreatitis. Role of sensory nerves. Eur J Pharmacol. 2008; 591(1-3): 284-292
14. Amalraj A, Pius A, Gopi S, Gopi S. Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives - A review. J Tradit Complement Med. 2016; 7(2): 205-233.
15. Anastasi A, Erspamer V, Endean R. Isolation and structure of caerulein, an active decapeptide from the skin of Hyla caerulea. Experientia. 1967; 23(9): 699-700.
16. Kim H. Cerulein pancreatitis: oxidative stress, inflammation, and apoptosis. Gut Liver. 2008; 2(2): 74-80.
17. Kannan N, Guruvayoorappan C. Protective effect of Bauhinia tomentosa on acetic acid induced ulcerative colitis by regulating antioxidant and inflammatory mediators. Int Immunopharmacol. 2013; 16(1): 57-66.
18. Klebanoff SJ, Kettle AJ, Rosen H, Winterbourn CC, Nauseef WM. Myeloperoxidase: a front-line defender against phagocytosed microorganisms. J Leukoc Biol. 2013; 93(2): 185-198.
19. Oruc N, Ozutemiz AO, Yukselen V, Nart D, Celik HA, Yuce G, Batur Y. Infliximab: a new therapeutic agent in acute pancreatitis? Pancreas. 2004; 28(1): e1-8.
20. Sharif R, Dawra R, Wasiluk K, Phillips P, Dudeja V, Kurt-Jones E, Finberg R, Saluja A. Impact of toll-like receptor 4 on the severity of acute pancreatitis and pancreatitis-associated lung injury in mice. Gut. 2009; 58(6): 813-819.
21. Pan LF, Yu L, Wang LM, He JT, Sun JL, Wang XB, Wang H, Bai ZH, Feng H, Pei HH. Augmenter of liver regeneration (ALR) regulates acute pancreatitis via inhibiting HMGB1/TLR4/NF-κB signaling pathway. Am J Transl Res. 2018; 10(2): 402-410.
22. Cen Y, Liu C, Li X, Yan Z, Kuang M, Su Y, Pan X, Qin R, Liu X, Zheng J, Zhou H. Artesunate ameliorates severe acute pancreatitis (SAP) in rats by inhibiting expression of pro-inflammatory cytokines and Toll-like receptor 4. Int Immunopharmacol. 2016; 38: 252-260.
23. Liu Z, Liu J, Zhao K, Shi Q, Zuo T, Wang G, Wang W. Role of Daphnetin in Rat Severe Acute Pancreatitis Through the Regulation of TLR4/NF-[Formula: see text]B Signaling Pathway Activation. Am J Chin Med. 2016; 44(1): 149-163.
24. Gulcubuk A, Altunatmaz K, Sonmez K, Haktanir-Yatkin D, Uzun H, Gurel A, Aydin S. 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(1): 49-54.
25. Seo SW, Bae GS, Kim SG, Yun SW, Kim MS, Yun KJ, Park RK, Song HJ, Park SJ. Protective effects of Curcuma longa against cerulein-induced acute pancreatitis and pancreatitis-associated lung injury. Int J Mol Med. 2011; 27(1): 53-61.
26. Gulcubuk A, Haktanir D, Cakiris A, Ustek D, Guzel O, Erturk M, Karabagli M, Akyazi I, Cicekci H, Altunatmaz K, Uzun H, Ates K. Effects of curcumin on proinflammatory cytokines and tissue injury in the early and late phases of experimental acute pancreatitis. Pancreatology. 2013; 13(4): 347-354.