• Kusmardi Kusmardi Department Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, 10430, Indonesia.
  • Dony Hermanto Department of Pharmacology & Therapeutics, Faculty of Medicine, Universitas Indonesia, 10430, Indonesia.
  • Ari Estuningytas Department of Pharmacology & Therapeutics, Faculty of Medicine, Universitas Indonesia, 10430, Indonesia.
  • Aryo Tedjo Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, 10430, Indonesia.
  • Bambang P Priosoeryanto Department of Veterinary Pathology, Faculty of Bogor Agricultural University, Bogor, Indonesia.



Inflammatory, Pomegranate peel, DSS, Cyclooxygenase-2, iNOS


Objective: Inflammatory disease occurs in the mucosal of the colon, or ulcerative colitis (UC) is one of subtypes of inflammatory bowel disease. The numerous of drug side effects for treatment of colitis give rise to use medicinal herbs as alternative therapies. Pomegranate peel extract has been used for the treatment of pain and inflammatory conditions. This study aimed to investigate the anti-inflammatory effects of pomegranate peel ethanol extract on mice colon through inflammation pathway which reduce inflammation score in mice model of chronic inflammation induced by dextran sodium sulfate (DSS).

Methods: Thirty Swiss Webster mice divided randomly into 6 groups: Normal, aspirin 43 mg/kg/d (ASP), ellagic acid 26 mg/kg/d (ELG), DSS 2%b/v (DSS), pomegranate peel ethanol extract 240 mg/kg/d (DOSES-1), and 480 mg/kg/d (DOSES-2). All groups were given DSS 2% over 3 cycles except normal group (where each cycle in the DSS group consisted of 2% DSS in drinking water for 7 days, followed by a 7-day interval with normal drinking water). At the end of the experiment, colon samples were washed with water then buffered neutral formalin 10% fixed and paraffin embedded for histological analysis.

Results: DOSES-1 and DOSES-2 were significantly reduced inflammation score in colon mice induced by DSS (p<0.05), mean score 2.01 and 2.02. Expression of cyclooxygenase (COX-2) was significantly decreased (p<0.05), mean score 27.48 and 17.77. Expression of iNOS was also significantly decreased (p<0.05), mean score 54.01 and 36.69. There were no significant differences between DOSES-1 and DOSES-2 groups with ASP and ELG group (p>0.05).

Conclusion: Pomegranate peel ethanol extract has an anti-inflammatory agent by reduces inflammation score, inhibiting COX-2 and iNOS expression on mice colon by DSS induced. Furthermore, pomegranate peel ethanol extract has equivalent effectiveness with aspirin and pure ellagic acid.


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Mulder DJ, Noble A, Justinich C, Duffin JM. A tile of two disease: The history of inflammatory bowel disease. J Crohn’s Colitis 2013;5:1-8.

Itzkowitz SH, Yio X. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: The role of inflammation. Am J Physiol Gastrointest Liver Physiol 2004;287(1):G7-17.

Lakatos PL, Lakatos L. Risk for colorectal cancer in ulcerative colitis: Changes, causes and management strategies. World J Gastroenterol 2008;14(25):3937-47.

Zhiqin W, Palaniappan S, Raja Ali RA. Inflammatory bowel disease-related colorectal cancer in the Asia-Pacific region: Past, present, and future. Intest Res 2014;12(3):194-204.

Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012;142(1):46-54.e420.

Perkumpulan Gastroenterologi Indonesia. Kelompok Studi Inflammatory Bowel Disease Indonesia, Konsensus Nasional Penatalaksanaan Inflammatory Bowel Disease (IBD) Di Indonesia. Jakarta: Perkumpulan Gastroenterologi Indonesia; 2011.

Sartor RB. Mechanisms of disease: Pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 2006;3(7):390-407.

Coskun M. Intestinal epithelium in inflammatory bowel disease. Front Med (Lausanne) 2014;1:1-5.

Siegmund B, Zeitz M. Innate and adaptive immunity in inflammatory bowel disease. World J Gastroenterol 2011;17(27):3178-83.

Abraham C, Medzhitov R. Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology 2011;140(6):1729-37.

Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 1999;18(49):6853-66.

Carter MJ, Lobo AJ, Travis SP; IBD Section, British Society of Gastroenterology. Guidelines for the management of inflammatory bowel disease in adults. Gut 2004;53 Suppl 5:V1-16.

Sales-Campos H, Basso PJ, Alves VB, Fonseca MT, Bonfá G, Nardini V, et al. Classical and recent advances in the treatment of inflammatory bowel diseases. Braz J Med Biol Res 2015;48(2):96-107.

Friis S, Riis AH, Erichsen R, Baron JA, Sørensen HT. Low-dose aspirin or nonsteroidal anti-inflammatory drug use and colorectal cancer risk: A population-based, case-control study. Ann Intern Med 2015;163(5):347-55.

Kaulmann A, Bohn T. Bioactivity of polyphenols: Preventive and adjuvant strategies toward reducing inflammatory bowel diseases-promises, perspectives, and pitfalls. Oxid Med Cell Longev 2016;2016:9346470.

Turrini E, Ferruzzi L, Fimognari C. Potential effects of pomegranate polyphenols in cancer prevention and therapy. Oxid Med Cell Longev 2015;2015:938475.

Panichayupakaranant P, Tewtrakul S, Yuenyongsawad S. Antibacterial, anti-inflammatory and antiallergic activities of standardized pomegranate rind extract. Food Chem 2010;123:400-3.

Hamza RZ, Abd El-Azez AM, Hussien NA. Evaluation of the antioxidant potential for different extracts of al-taif pomegranate (Punica granatum L) induced by atrazine and Malathion pesticides in liver of male albino mice. Int J Pharm Pharm Sci 2015;7 Suppl 1:89-94.

Gadouche L, Djebli N, Zerrouki K. Neuroprotective effects of pomegranate juice on lead induced neurotoxicity in mice. Int J Pharm Pharm Sci 2016;9 Suppl 2:207-12.

Rosillo MA, Sánchez-Hidalgo M, Cárdeno A, Aparicio-Soto M, Sánchez-Fidalgo S, Villegas I, et al. Dietary supplementation of an ellagic acid-enriched pomegranate extract attenuates chronic colonic inflammation in rats. Pharmacol Res 2012;66(3):235-42.

Neyrinck AM, Van Hée VF, Bindels LB, De Backer F, Cani PD, Delzenne NM. Polyphenol-rich extract of pomegranate peel alleviates tissue inflammation and hypercholesterolaemia in high-fat diet-induced obese mice: Potential implication of the gut microbiota. Br J Nutr 2013;109(5):802-9.

Jimenez Del Rio M, Ramazanov A, Sikorski S, Ramazanov Z, Chkhikvishvili I. A new method of standartization of health-promoting pomegranate fruit (Punica granatum) extract. Georgian Med News 2006;140:70-7.

US FDA. Guidance for Industry: Estimating the Maximum Safe Starting Dose in Adult Healthy Volunteer. Rockville, MD: US Food and Drug Administration; 2005.

al-Swayeh OA, Clifford RH, del Soldato P, Moore PK. A comparison of the anti-inflammatory and anti-nociceptive activity of nitroaspirin and aspirin. Br J Pharmacol 2000;129(2):343-50.

Panichayupakarananta P, Issuriya A, Sirikatitham A, Wang W. Antioxidant assay-guided purification and LC determination of ellagic acid in pomegranate peel. J Chromatogr Sci 2010;48(6):456-9.

Rogers R, Anderson JE, De Voss J, Lesch J, Yan D, Xu M, et al. Image analysis-based approaches for scoring mouse models of colitis. Vet Pathol 2015;1:1-11.

Detre S, Saclani Jotti G, Dowsett M. A quickscore’ method for immunohistochemical semiquantitation: Validation for oestrogen receptor in breast carcinomas. J Clin Pathol 1995;48(9):876-8.

Chassaing B, Aitken JD, Malleshappa M, Vijay-Kumar M. Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol 2014;104:1-16.

Solomon L, Mansor S, Mallon P, Donelly E, Hoper M, Loughrey M, et al. The dextran sulphate sodium: An ovierview. Comp Clin Pathol 2010;19:235-9.

Perše M, Cerar A. Dextran sodium sulphate colitis mouse model: Traps and tricks. J Biomed Biotechnol 2012;2012:718617.

Paul-Clark MJ, Van Cao T, Moradi-Bidhendi N, Cooper D, Gilroy DW. 15-epi-lipoxin A4-mediated induction of nitric oxide explains how aspirin inhibits acute inflammation. J Exp Med 2004;200(1):69-78.

Pasparakis M. IKK, NF-Κb signaling in intestinal epithelial cells controls immune homeostasis in the gut. Mucosal Immunol Nat 2008;1:S54-7.

Dovizio M, Tacconelli S, Sostres C, Ricciotti E, Patrignani P. Mechanistic and pharmacological issues of aspirin as an anticancer agent. Pharmaceuticals (Basel) 2012;5(12):1346-71.

Patrono C, Baigent C, Hirsh J, Roth G. Antiplatelet drugs: American college of chest physicians evidence-based clinical practice guidelines (8th edition). Chest 2008;133 6 Suppl:199S-233.

Sidhu RS, Lee JY, Yuan C, Smith WL. Comparison of cyclooxygenase-1 crystal structures: Cross-talk between monomers comprising cyclooxygenase-1 homodimers. Biochemistry 2010;49(33):7069-79.

Rimon G, Sidhu RS, Lauver DA, Lee JY, Sharma NP, Yuan C, et al. Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1. Proc Natl Acad Sci U S A 2010;107(1):28-33.

Sharma NP, Dong L, Yuan C, Noon KR, Smith WL. Asymmetric acetylation of the cyclooxygenase-2 homodimer by aspirin and its effects on the oxygenation of arachidonic, eicosapentaenoic, and docosahexaenoic acids. Mol Pharmacol 2010;77(6):979-86.

Gilroy DW. New insights into the anti-inflammatory actions of aspirin-induction of nitric oxide through the generation of epi-lipoxins. Mem Inst Oswaldo Cruz 2005;100 Suppl 1:49-54.

Köhnke T, Gomolka B, Bilal S, Zhou X, Sun Y, Rothe M, et al. Acetylsalicylic acid reduces the severity of dextran sodium sulfate-induced colitis and increases the formation of anti-inflammatory lipid mediators. Biomed Res Int 2013;2013:748160.

Bellik Y, Boukraâ L, Alzahrani HA, Bakhotmah BA, Abdellah F, Hammoudi SM, et al. Molecular mechanism underlying anti-inflammatory and anti-allergic activities of phytochemicals: An update. Molecules 2012;18(1):322-53.

Karlsson S, NÃ¥nberg E, Fjaeraa C, Wijkander J. Ellagic acid inhibits lipopolysaccharide-induced expression of enzymes involved in the synthesis of prostaglandin E2 in human monocytes. Br J Nutr 2010;103(8):1102-9.

Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 1998;38:97-120.

Kolios G, Valatas V, Ward SG. Nitric oxide in inflammatory bowel disease: A universal messenger in an unsolved puzzle. Immunology 2004;113(4):427-37.

Miller MJ, Sandoval M. Nitric oxide. III. A molecular prelude to intestinal inflammation. Am J Physiol 1999;276:G795-9.

Larrosa M, González-Sarrías A, Yáñez-Gascón MJ, Selma MV, Azorín-Ortuño M, Toti S, et al. Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism. J Nutr Biochem 2010;21(8):717-25.

Marín M, María Giner R, Ríos JL, Recio MC. Intestinal anti-inflammatory activity of ellagic acid in the acute and chronic dextrane sulfate sodium models of mice colitis. J Ethnopharmacol 2013;150(3):925-34.

Khan MK, Ansari IA, Khan MS, Arif JM. Dietary phytochemicals as potent chemotherapeutic agents against breast cancer: Inhibition of NF-κB pathway via molecular interactions in rel homology domain of its precursor protein p105. Pharmacogn Mag 2013;9:51-7.



How to Cite

Kusmardi, K., D. Hermanto, A. Estuningytas, A. Tedjo, and B. P. Priosoeryanto. “THE POTENCY OF INDONESIA’S POMEGRANATE PEEL ETHANOL EXTRACT (PUNICA GRANATUM LINN.) AS ANTI-INFLAMMATORY AGENT IN MICE COLON INDUCED BY DEXTRAN SODIUM SULFATE: FOCUS ON CYCLOOXYGENASE-2 AND INOS EXPRESSIONS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 10, no. 12, Dec. 2017, pp. 370-5, doi:10.22159/ajpcr.2017.v10i12.21390.



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