Protective Effect of Zerumbone on Pancreatic Injury in Severe Acute Pancreatitis via NF-κB_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 DENGWen-hong , GUOWen-yi , SUNRong-ze , XIANGMing-wei , ZHAOLiang , SHIQiao ,  WANGWei-xing

Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China;

Corresponding?author：

WANGWei-xing, Email: sate.llite@163.com

Keywords：

Zerumbone; Acute pancreatitis; Nuclear factor-kappa B

DOI：

10.7507/1007-9424.20160007

Video：

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Objective To investigate the possible protective effect of zerumbone on pancreatic injury in severe acute pancreatitis (SAP) rats, and to provide a theoretical basis for prevention and treatmen of severe acute pancreatitis. Methods Seventy male Wistar rats were randomly divided into four groups:normal control group (NC group, n=10), SAP group (n=40), Zerumbone pretreatment group (ZER group, n=10), and Zerumbone drug control group (ZER-CON group, n=10). Rats of SAP group were divided into four time points of 1 h, 3 h, 6 h, and 12 h (n=10 each time point). SAP models were induced by retrograde injection of 5% sodium taurocholate (0.1 mL/100 g) in biliopancreatic duct in SAP group and ZER group. Rats were injected isotonic saline solution instead of taurocholate as a control in NC group and ZER-CON group. Zerumbone solution (10 mg/kg) was administered via femoral vein half an hour prior to establishing models in ZER group and ZER-CON group. All rats except SAP group were sacrificed at 12 h time point after the induction of SAP. The rats in SAP group were sacrificed at 1 h, 1 h, 3 h, 6 h and 12 h time point after induction of SAP. The mortality, ascites, serum amylase (AMY), phospholipase, and pathological examination of pancreas were observated or detected. The expression of nuclear factor-kappa B (NF-κB) p65 in pancreatic tissues was evaluated by immunohistochemistry assay. Results There were no difference of the levels of mortality, ascites, serum AMY, phospholipase, pathological examination, and NF-κB p65 location expression of pancreas between the ZER-CON group and NC group (P>0.05). The above indexes in SAP group were significantly higher than those in NC group (P<0.05). However, those in ZER group were significantly lower than in SAP group (P<0.05), and higher than in NC group (P<0.05). Conclusions Zerumbone can reduce the mortality and ascites, effectively alleviate the enzyme, pathological injury, and NF-κB p65 location expression in pancreatic tissue following SAP. It may indicate that zerumbone can protect pancreatic injury in SAP via NF-κB pathway.

Citation： DENGWen-hong, GUOWen-yi, SUNRong-ze, XIANGMing-wei, ZHAOLiang, SHIQiao, WANGWei-xing. Protective Effect of Zerumbone on Pancreatic Injury in Severe Acute Pancreatitis via NF-κB. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(1): 28-32. doi: 10.7507/1007-9424.20160007 Copy

1.	?GrangerJ, Remick D. Acute pancreatitis:models, markers, and mediators. Shock, 2005, 24 Suppl 1:45-51.
2.	殷濤, 王春友. 重癥急性胰腺炎多學科綜合治療的重點和難點. 中華普通外科雜志, 2015, 30(1):1-3.
3.	Sulaiman MR, Perimal EK, Akhtar MN, et al. Anti-inflammatory effect of zerumbone on acute and chronic inflammation models in mice. Fitoterapia, 2010, 81(7):855-858.
4.	Chien TY, Chen LG, Lee CJ, et al. Anti-inflammatory constituents of Zingiber zerumbet. Food Chemistry, 2008, 110(3):584-589.
5.	Chan ML, Liang JW, Hsu LC, et al. Zerumbone, a ginger sesquiter-pene, induces apoptosis and autophagy in human hormone-refrac-tory prostate cancers through tubulin binding and crosstalk between endoplasmic reticulum stress and mitochondrial insult. Naunyn Schmiedebergs Arch Pharmacol, 2015, 388(11):1223-1236.
6.	李金友, 王衛星, 鄧文宏, 等. 不同劑量花姜酮對大鼠重癥急性胰腺炎的影響. 微循環學雜志, 2010, 20(3):14-15.
7.	Schmidt J, Rattner DW, Lewandrowski K, et al. A better model of acute pancreatitis for evaluating therapy. Ann Surg, 1992, 215(1):44-56.
8.	Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis-2012:revision of the Atlanta classification and defini-tions by international consensus. Gut, 2013, 62(1):102-111.
9.	陳宏, 孫家邦, 朱研, 等. 重癥急性胰腺炎早期液體治療策略的探討. 中國普外基礎與臨床雜志, 2012, 19(5):507-511.
10.	姚欣敏, 張抒, 李云濤, 等. 不同時期重癥急性胰腺炎治療的對照研究. 中國普外基礎與臨床雜志, 2011, 18(3):245-249.
11.	葉健, 莫顯斌. CT分級診斷在急性胰腺炎臨床治療中的價值. 中國普外基礎與臨床雜志, 2010, 17(12):1322-1325.
12.	吳麗, 蔡寶昌. 重癥急性胰腺炎肝損傷機制及中醫藥治療的研究進展. 南京中醫藥大學學報, 2013, 29(4):393-396.
13.	鐘健, 劉麗, 劉大晟, 等. 桃核承氣湯對重癥急性胰腺炎模型大鼠炎癥因子的調控作用及機制. 中國老年學雜志, 2015, 35(12):3223-3226.
14.	Kitayama T, Okamoto T, Hill RK, et al. Chemistry of zerumbone. 1. Simplified isolation, conjugate addition reactions, and a unique ring contracting transannular reaction of its dibromide. J Org Chem, 1999, 64(8):2667-2672.
15.	Shanmugam MK, Rajendran P, Li F, et al. Abrogation of STAT3 signaling cascade by zerumbone inhibits proliferation and induces apoptosis in renal cell carcinoma xenograft mouse model. Mol Carcinog, 2015, 54(10):971-985.
16.	Shieh YH, Huang HM, Wang CC, et al. Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2 responses and airway inflammation in mice. Int Immunopharmacol, 2015, 24(2):383-391.
17.	Wang CY, Zou SB, Cui ZJ, et al. Zerumbone protects INS-1 rat pancreatic beta cells from high glucose-induced apoptosis through generation of reactive oxygen species. Biochem Biophys Res Commun, 2015, 460(2):205-209.
18.	Murakami A, Hayashi R, Tanaka T, et al. Suppression of dextran sodium sulfate-induced colitis in mice by zerumbone, a subtropical ginger sesquiterpene, and nimesulide:separately and in combination. Biochem Pharmacol, 2003, 66(7):1253-1261.
19.	Murakami A, Ohigashi H. Targeting NOX, INOS and COX-2 in inflammatory cells:chemoprevention using food phytochemicals. Int J Cancer, 2007, 121(11):2357-2363.
20.	Murakami A, Takahashi D, Kinoshita T, et al. Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis:the alpha,beta-unsaturated carbonyl group is a prerequisite. Carcinogenesis, 2002, 23(5):795-802.
21.	Telek G, Ducroc R, Scoazec JY, et al. Differential upregulation of cellular adhesion molecules at the sites of oxidative stress in experimental acute pancreatitis. J Surg Res, 2001, 96(1):56-67.
22.	Chen X, Ji B, Han B, et al. NF-kappaB activation in pancreas induces pancreatic and systemic inflammatory response. Gastroenterology, 2002, 122(2):448-457.
23.	Ding J, Song D, Ye X, et al. A pivotal role of endothelial-specific NF-kappaB signaling in the pathogenesis of septic shock and septic vascular dysfunction. J Immunol, 2009, 183(6):4031-4038.
24.	鄭邦瑞, 沈文律, 文軍, 等. 丹參注射液對重癥急性胰腺炎大鼠胰腺NF-κB活化的影響. 中國普外基礎與臨床雜志, 2007, 14(4):392-395.
25.	Manavalan B, Basith S, Choi YM, et al. Structure-function relation-ship of cytoplasmic and nuclear IκB proteins:an in silico analysis. PLoS One, 2010, 5(12):e15782.
26.	Murakami A, Matsumoto K, Koshimizu K, et al., Effects of selected food factors with chemopreventive properties on combined lipopo-lysaccharide-and interferon-gamma-induced I kappa B degradation in RAW264.7 macrophages. Cancer Lett, 2003, 195(1):17-25.
27.	Sung B, Murakami A, Oyajobi BO, et al. Zerumbone abolishes RANKL-induced NF-kappaB activation, inhibits osteoclastogenesis, and suppresses human breast cancer-induced bone loss in athymic nude mice. Cancer Res, 2009, 69(4):1477-1484.
28.	Takada Y, Murakami A, Aggarwal BB. Zerumbone abolishes NF-kappa B and I kappa B alpha kinase activation leading to suppre-ssion of antiapoptotic and metastatic gene expression, upregulation of apoptosis, and downregulation of invasion. Oncogene, 2005, 24(46):6957-6969.
29.	Aggarwal BB, Kunnumakkara AB, Harikumar KB, et al. Potential of spice-derived phytochemicals for cancer prevention. Planta Med, 2008, 74(13):1560-1569.

1. ?GrangerJ, Remick D. Acute pancreatitis:models, markers, and mediators. Shock, 2005, 24 Suppl 1:45-51.
2. 殷濤, 王春友. 重癥急性胰腺炎多學科綜合治療的重點和難點. 中華普通外科雜志, 2015, 30(1):1-3.
3. Sulaiman MR, Perimal EK, Akhtar MN, et al. Anti-inflammatory effect of zerumbone on acute and chronic inflammation models in mice. Fitoterapia, 2010, 81(7):855-858.
4. Chien TY, Chen LG, Lee CJ, et al. Anti-inflammatory constituents of Zingiber zerumbet. Food Chemistry, 2008, 110(3):584-589.
5. Chan ML, Liang JW, Hsu LC, et al. Zerumbone, a ginger sesquiter-pene, induces apoptosis and autophagy in human hormone-refrac-tory prostate cancers through tubulin binding and crosstalk between endoplasmic reticulum stress and mitochondrial insult. Naunyn Schmiedebergs Arch Pharmacol, 2015, 388(11):1223-1236.
6. 李金友, 王衛星, 鄧文宏, 等. 不同劑量花姜酮對大鼠重癥急性胰腺炎的影響. 微循環學雜志, 2010, 20(3):14-15.
7. Schmidt J, Rattner DW, Lewandrowski K, et al. A better model of acute pancreatitis for evaluating therapy. Ann Surg, 1992, 215(1):44-56.
8. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis-2012:revision of the Atlanta classification and defini-tions by international consensus. Gut, 2013, 62(1):102-111.
9. 陳宏, 孫家邦, 朱研, 等. 重癥急性胰腺炎早期液體治療策略的探討. 中國普外基礎與臨床雜志, 2012, 19(5):507-511.
10. 姚欣敏, 張抒, 李云濤, 等. 不同時期重癥急性胰腺炎治療的對照研究. 中國普外基礎與臨床雜志, 2011, 18(3):245-249.
11. 葉健, 莫顯斌. CT分級診斷在急性胰腺炎臨床治療中的價值. 中國普外基礎與臨床雜志, 2010, 17(12):1322-1325.
12. 吳麗, 蔡寶昌. 重癥急性胰腺炎肝損傷機制及中醫藥治療的研究進展. 南京中醫藥大學學報, 2013, 29(4):393-396.
13. 鐘健, 劉麗, 劉大晟, 等. 桃核承氣湯對重癥急性胰腺炎模型大鼠炎癥因子的調控作用及機制. 中國老年學雜志, 2015, 35(12):3223-3226.
14. Kitayama T, Okamoto T, Hill RK, et al. Chemistry of zerumbone. 1. Simplified isolation, conjugate addition reactions, and a unique ring contracting transannular reaction of its dibromide. J Org Chem, 1999, 64(8):2667-2672.
15. Shanmugam MK, Rajendran P, Li F, et al. Abrogation of STAT3 signaling cascade by zerumbone inhibits proliferation and induces apoptosis in renal cell carcinoma xenograft mouse model. Mol Carcinog, 2015, 54(10):971-985.
16. Shieh YH, Huang HM, Wang CC, et al. Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2 responses and airway inflammation in mice. Int Immunopharmacol, 2015, 24(2):383-391.
17. Wang CY, Zou SB, Cui ZJ, et al. Zerumbone protects INS-1 rat pancreatic beta cells from high glucose-induced apoptosis through generation of reactive oxygen species. Biochem Biophys Res Commun, 2015, 460(2):205-209.
18. Murakami A, Hayashi R, Tanaka T, et al. Suppression of dextran sodium sulfate-induced colitis in mice by zerumbone, a subtropical ginger sesquiterpene, and nimesulide:separately and in combination. Biochem Pharmacol, 2003, 66(7):1253-1261.
19. Murakami A, Ohigashi H. Targeting NOX, INOS and COX-2 in inflammatory cells:chemoprevention using food phytochemicals. Int J Cancer, 2007, 121(11):2357-2363.
20. Murakami A, Takahashi D, Kinoshita T, et al. Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis:the alpha,beta-unsaturated carbonyl group is a prerequisite. Carcinogenesis, 2002, 23(5):795-802.
21. Telek G, Ducroc R, Scoazec JY, et al. Differential upregulation of cellular adhesion molecules at the sites of oxidative stress in experimental acute pancreatitis. J Surg Res, 2001, 96(1):56-67.
22. Chen X, Ji B, Han B, et al. NF-kappaB activation in pancreas induces pancreatic and systemic inflammatory response. Gastroenterology, 2002, 122(2):448-457.
23. Ding J, Song D, Ye X, et al. A pivotal role of endothelial-specific NF-kappaB signaling in the pathogenesis of septic shock and septic vascular dysfunction. J Immunol, 2009, 183(6):4031-4038.
24. 鄭邦瑞, 沈文律, 文軍, 等. 丹參注射液對重癥急性胰腺炎大鼠胰腺NF-κB活化的影響. 中國普外基礎與臨床雜志, 2007, 14(4):392-395.
25. Manavalan B, Basith S, Choi YM, et al. Structure-function relation-ship of cytoplasmic and nuclear IκB proteins:an in silico analysis. PLoS One, 2010, 5(12):e15782.
26. Murakami A, Matsumoto K, Koshimizu K, et al., Effects of selected food factors with chemopreventive properties on combined lipopo-lysaccharide-and interferon-gamma-induced I kappa B degradation in RAW264.7 macrophages. Cancer Lett, 2003, 195(1):17-25.
27. Sung B, Murakami A, Oyajobi BO, et al. Zerumbone abolishes RANKL-induced NF-kappaB activation, inhibits osteoclastogenesis, and suppresses human breast cancer-induced bone loss in athymic nude mice. Cancer Res, 2009, 69(4):1477-1484.
28. Takada Y, Murakami A, Aggarwal BB. Zerumbone abolishes NF-kappa B and I kappa B alpha kinase activation leading to suppre-ssion of antiapoptotic and metastatic gene expression, upregulation of apoptosis, and downregulation of invasion. Oncogene, 2005, 24(46):6957-6969.
29. Aggarwal BB, Kunnumakkara AB, Harikumar KB, et al. Potential of spice-derived phytochemicals for cancer prevention. Planta Med, 2008, 74(13):1560-1569.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Protective Effect of Zerumbone on Pancreatic Injury in Severe Acute Pancreatitis via NF-κB

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