Open Access

Curcumin protects the pancreas from acute pancreatitis via the mitogen‑activated protein kinase signaling pathway

  • Authors:
    • Yingjie Wang
    • Chanyuan Bu
    • Kangkang Wu
    • Rui Wang
    • Jiayong Wang
  • View Affiliations

  • Published online on: August 1, 2019     https://doi.org/10.3892/mmr.2019.10547
  • Pages: 3027-3034
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

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.

References

1 

Golay V and Roychowdhary A: Acute pancreatitis in chronic kidney disease-a common but often misunderstood combination. Ren Fail. 34:1338–1340. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Cavestro GM, Leandro G, Di Leo M, Zuppardo RA, Morrow OB, Notaristefano C, Rossi G, Testoni SG, Mazzoleni G, Alessandri M, et al: A single-centre prospective, cohort study of the natural history of acute pancreatitis. Dig Liver Dis. 47:205–210. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Okuturlar Y, Soylu A, Dogan H, Cakmak S, Kirac Utku I, Oztosun B, Akarsu C, Ocak Serin S, Avci A, Kones O, et al: Mean platelet volume in patients with biliary and non-biliary acute pancreatitis. Int J Clin Exp Pathol. 8:2051–2056. 2015.PubMed/NCBI

4 

Albulushi A, Siddiqi A, Alqarshoubi I, Aladawi M, Alkhadhouri G and Farhan H: Pattern of acute pancreatitis in a tertiary care center in oman. Oman Med J. 29:358–361. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Dabrowski A, Osada J, Dabrowska MI, Wereszczynska-Siemiatkowska U and Siemiatkowski A: Increased expression of the intercellular adhesion molecule-1 (ICAM-1) on peripheral blood neutrophils in acute pancreatitis. Adv Med Sci. 59:102–107. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Shen SQ, Zhang Y, Xiang JJ and Xiong CL: Protective effect of curcumin against liver warm ischemia/reperfusion injury in rat model is associated with regulation of heat shock protein and antioxidant enzymes. World J Gastroenterol. 13:1953–1961. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Jurenka JS: Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: A review of preclinical and clinical research. Altern Med Rev. 14:141–153. 2009.PubMed/NCBI

8 

Anchi P, Khurana A, Swain D, Samanthula G and Godugu C: Sustained-release curcumin microparticles for effective prophylactic treatment of exocrine dysfunction of pancreas: A preclinical study on cerulein-induced acute pancreatitis. J Pharm Sci. 107:2869–2882. 2018. View Article : Google Scholar : PubMed/NCBI

9 

Zhu S, Zhang C, Weng Q and Ye B: Curcumin protects against acute renal injury by suppressing JAK2/STAT3 pathway in severe acute pancreatitis in rats. Exp Ther Med. 14:1669–1674. 2017. View Article : Google Scholar : PubMed/NCBI

10 

Zhai KF, Duan H, Khan GJ, Xu H, Han FK, Cao WG, Gao GZ, Shan LL and Wei ZJ: Salicin from alangium chinense ameliorates rheumatoid arthritis by modulating the Nrf2-HO-1-ROS pathways. J Agric Food Chem. 66:6073–6082. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Dugernier TL, Laterre PF, Wittebole X, Roeseler J, Latinne D, Reynaert MS and Pugin J: Compartmentalization of the inflammatory response during acute pancreatitis: Correlation with local and systemic complications. Am J Respir Crit Care Med. 168:148–157. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Polyzogopoulou E, Bikas C, Danikas D, Koutras A, Kalfarentzos F and Gogos CA: Baseline hypoxemia as a prognostic marker for pulmonary complications and outcome in patients with acute pancreatitis. Dig Dis Sci. 49:150–154. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Cöl C, Dinler K, Hasdemir AO and Bugdayci G: The effect of an intraperitoneal injection of melatonin on serum amylase levels in acute pancreatitis. JOP. 10:306–309. 2009.PubMed/NCBI

14 

Bonior J, Warzecha Z, Ceranowicz P, Gajdosz R, Pierzchalski P, Kot M, Leja-Szpak A, Nawrot-Porąbka K, Link-Lenczowski P, Pędziwiatr M, et al: Capsaicin-sensitive sensory nerves are necessary for the protective effect of ghrelin in cerulein-induced acute pancreatitis in rats. Int J Mol Sci. 18(pii): E14022017. View Article : Google Scholar : PubMed/NCBI

15 

Bishehsari F, Sharma A, Stello K, Toth C, O'Connell MR, Evans AC, LaRusch J, Muddana V, Papachristou GI and Whitcomb DC: TNF-alpha gene (TNFA) variants increase risk for multi-organ dysfunction syndrome (MODS) in acute pancreatitis. Pancreatology. 12:113–118. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Malleo G, Mazzon E, Siriwardena AK and Cuzzocrea S: Role of tumor necrosis factor-alpha in acute pancreatitis: From biological basis to clinical evidence. Shock. 28:130–140. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Culić O, Eraković V, Cepelak I, Barisić K, Brajsa K, Ferencić Z, Galović R, Glojnarić I, Manojlović Z, Munić V, et al: Azithromycin modulates neutrophil function and circulating inflammatory mediators in healthy human subjects. Eur J Pharmacol. 450:277–289. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Bezmarevic M, Mirkovic D, Soldatovic I, Stamenkovic D, Mitrovic N, Perisic N, Marjanovic I, Mickovic S and Karanikolas M: Correlation between procalcitonin and intra-abdominal pressure and their role in prediction of the severity of acute pancreatitis. Pancreatology. 12:337–343. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Zhong K: Curcumin Mediates a Protective effect via TLR-4/NF-κB signaling pathway in rat model of severe acute pancreatitis. Cell Biochem Biophys. 73:175–180. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Gulcubuk A, Altunatmaz K, Sonmez K, Haktanir-Yatkin D, Uzun H, Gurel A and 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. 53:49–54. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Fisic E, Poropat G, Bilic-Zulle L, Licul V, Milic S and Stimac D: The role of IL-6, 8, and 10, sTNFr, CRP, and pancreatic elastase in the prediction of systemic complications in patients with acute pancreatitis. Gastroenterol Res Pract. 2013:2826452013. View Article : Google Scholar : PubMed/NCBI

22 

Bimonte S, Barbieri A, Palma G, Luciano A, Rea D and Arra C: Curcumin inhibits tumor growth and angiogenesis in an orthotopic mouse model of human pancreatic cancer. Biomed Res Int. 2013:8104232013. View Article : Google Scholar : PubMed/NCBI

23 

Qin T, Fu Q, Pan YF, Liu CJ, Wang YZ, Hu MX, Tang Q and Zhang HW: Expressions of miR-22 and miR-135a in acute pancreatitis. J Huazhong Univ Sci Technolog Med Sci. 34:225–233. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Patel K, Durgampudi C, Noel P, Trivedi RN, de Oliveira C and Singh VP: Fatty acid ethyl esters are less toxic than their parent fatty acids generated during acute pancreatitis. Am J Pathol. 186:874–884. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Talukdar R, Sareen A, Zhu H, Yuan Z, Dixit A, Cheema H, George J, Barlass U, Sah R, Garg SK, et al: Release of cathepsin b in cytosol causes cell death in acute pancreatitis. Gastroenterology. 151:747–758.e5. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Yu S, Wang M, Guo X and Qin R: Curcumin attenuates inflammation in a severe acute pancreatitis animal model by regulating TRAF1/ASK1 signaling. Med Sci Monit. 24:2280–2286. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Samuel I, Zaheer A and Fisher RA: In vitro evidence for role of ERK, p38, and JNK in exocrine pancreatic cytokine production. J Gastrointest Surg. 10:1376–1383. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Chen P, Huang L, Zhang Y, Qiao M and Yuan Y: SiRNA-mediated PIAS1 silencing promotes inflammatory response and leads to injury of cerulein-stimulated pancreatic acinar cells via regulation of the P38MAPK signaling pathway. Int J Mol Med. 26:619–626. 2010.PubMed/NCBI

29 

Kim D and Haynes CL: The role of p38 MAPK in neutrophil functions: Single cell chemotaxis and surface marker expression. Analyst. 138:6826–6833. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Kim HA, Kim KJ, Seo KH, Lee HK and Im SY: PTEN/MAPK pathways play a key role in platelet-activating factor-induced experimental pulmonary tumor metastasis. FEBS Lett. 586:4296–4302. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Lee SJ, Kim WJ and Moon SK: Role of the p38 MAPK signaling pathway in mediating interleukin-28A-induced migration of UMUC-3 cells. Int J Mol Med. 30:945–952. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October 2019
Volume 20 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Wang, Y., Bu, C., Wu, K., Wang, R., & Wang, J. (2019). Curcumin protects the pancreas from acute pancreatitis via the mitogen‑activated protein kinase signaling pathway. Molecular Medicine Reports, 20, 3027-3034. https://doi.org/10.3892/mmr.2019.10547
MLA
Wang, Y., Bu, C., Wu, K., Wang, R., Wang, J."Curcumin protects the pancreas from acute pancreatitis via the mitogen‑activated protein kinase signaling pathway". Molecular Medicine Reports 20.4 (2019): 3027-3034.
Chicago
Wang, Y., Bu, C., Wu, K., Wang, R., Wang, J."Curcumin protects the pancreas from acute pancreatitis via the mitogen‑activated protein kinase signaling pathway". Molecular Medicine Reports 20, no. 4 (2019): 3027-3034. https://doi.org/10.3892/mmr.2019.10547