Anti-Inflammatory Effects of a Pomegranate Leaf Extract in LPS-Induced Peritonitis

Abstract

Folk medicine suggests that pomegranate (peels, seeds and leaves) has anti-inflammatory properties; however, the precise mechanisms by which this plant affects the inflammatory process remain unclear. Herein, we analyzed the anti-inflammatory properties of a hydroalcoholic extract prepared from pomegranate leaves using a rat model of lipopolysaccharide-induced acute peritonitis. Male Wistar rats were treated with either the hydroalcoholic extract, sodium diclofenac, or saline, and 1 h later received an intraperitoneal injection of lipopolysaccharides. Saline-injected animals (i. p.) were used as controls. Animals were culled 4 h after peritonitis induction, and peritoneal lavage and peripheral blood samples were collected. Serum and peritoneal lavage levels of TNF-α as well as TNF-α mRNA expression in peritoneal lavage leukocytes were quantified. Total and differential leukocyte populations were analyzed in peritoneal lavage samples. Lipopolysaccharide-induced increases of both TNF-α mRNA and protein levels were diminished by treatment with either pomegranate leaf hydroalcoholic extract (57 % and 48 % mean reduction, respectively) or sodium diclofenac (41 % and 33 % reduction, respectively). Additionally, the numbers of peritoneal leukocytes, especially neutrophils, were markedly reduced in hydroalcoholic extract-treated rats with acute peritonitis. These results demonstrate that pomegranate leaf extract may be used as an anti-inflammatory drug which suppresses the levels of TNF-α in acute inflammation.

Key words

Punica granatum - Punicaceae - anti-inflammatory effect - cytokine - neutrophils - pomegranate

• References

• 1 Kalliolias GD, Ivashkiv LB. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol 2016; 12: 49-62
• 2 Bradley JR. TNF-mediated inflammatory disease. J Pathol 2008; 214: 149-160
• 3 Cairns JA. The coxibs and traditional nonsteroidal anti-inflammatory drugs: a current perspective on cardiovascular risks. Can J Cardiol 2007; 23: 125-131
• 4 Barnes PJ. How corticosteroids control inflammation: Quintiles Prize Lecture 2005. Br J Pharmacol 2006; 148: 245-254
• 5 Allez M, Vermeire S, Mozziconacci N, Michetti P, Laharie D, Louis E, Bigard MA, Hebuterne X, Treton X, Kohn A, Marteau P, Cortot A, Nichita C, van Assche G, Rutgeerts P, Lémann M, Colombel JF. The efficacy and safety of a third anti-TNF monoclonal antibody in Crohnʼs disease after failure of two other anti-TNF antibodies. Aliment Pharmacol Ther 2010; 31: 92-101
• 6 Pan X, Cao X, Li N, Xu Y, Wu Q, Bai J, Yin Z, Luo L, Lan L. Forsythin inhibits lipopolysaccharide-induced inflammation by suppressing JAK-STAT and p38 MAPK signalings and ROS production. Inflamm Res 2014; 63: 597-608
• 7 Prakash Babu N, Saravanan S, Pandikumar P, Bala Krishna K, Karunai Raj M, Ignacimuthu S. Anti-inflammatory and anti-arthritic effects of 3-hydroxy, 2-methoxy sodium butanoate from the leaves of Clerodendrum phlomidis L.f. Inflamm Res 2014; 63: 127-138
• 8 Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol 2007; 109: 177-206
• 9 Nayak SB, Rodrigues V, Maharaj S, Bhogadi VS. Wound healing activity of the fruit skin of Punica granatum . J Med Food 2013; 16: 857-861
• 10 Reddy MK, Gupta SK, Jacob MR, Khan SI, Ferreira D. Antioxidant, antimalarial and antimicrobial activities of tannin-rich fractions, ellagitannins and phenolic acids from Punica granatum L. Planta Med 2007; 73: 461-467
• 11 Al-Jarallah A, Igdoura F, Zhang Y, Tenedero CB, White EJ, MacDonald ME, Igdoura SA, Trigatti BL. The effect of pomegranate extract on coronary artery atherosclerosis in SR-BI/APOE double knockout mice. Atherosclerosis 2013; 228: 80-89
• 12 Wu PT, Fitschen PJ, Kistler BM, Jeong JH, Chung HR, Aviram M, Phillips SA, Fernhall B, Wilund KR. Effects of pomegranate extract supplementation on cardiovascular risk factors and physical function in hemodialysis patients. J Med Food 2015; 18: 941-949
• 13 Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. ScientificWorldJournal 2013; 2013: 162750
• 14 Wang Y, Chen P, Tang C, Li Y, Zhang H. Antinociceptive and anti-inflammatory activities of extract and two isolated flavonoids of Carthamus tinctorius L. J Ethnopharmacol 2014; 151: 944-950
• 15 Kritas SK, Saggini A, Varvara G, Murmura G, Caraffa A, Antinolfi P, Toniato E, Pantalone A, Neri G, Frydas S, Rosati M, Tei M, Speziali A, Saggini R, Pandolfi F, Cerulli G, Theoharides TC, Conti P. Luteolin inhibits mast cell-mediated allergic inflammation. J Biol Regul Homeost Agents 2013; 27: 955-959
• 16 De Oliveira JF, Garreto DV, da Silva MC, Fortes TS, de Oliveira RB, Nascimento FR, Da Costa FB, Grisotto MA, Nicolete R. Therapeutic potential of biodegradable microparticles containing Punica granatum L. (pomegranate) in murine model of asthma. Inflamm Res 2013; 62: 971-980
• 17 Mo J, Panichayupakaranant P, Kaewnopparat N, Nitiruangjaras A, Reanmongkol W. Topical anti-inflammatory and analgesic activities of standardized pomegranate rind extract in comparison with its marker compound ellagic acid in vivo . J Ethnopharmacol 2013; 148: 901-908
• 18 Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 2003; 3: 745-756
• 19 Bachoual R, Talmoudi W, Boussetta T, Braut F, El-Benna J. An aqueous pomegranate peel extract inhibits neutrophil myeloperoxidase in vitro and attenuates lung inflammation in mice. Food Chem Toxicol 2011; 49: 1224-1228
• 20 Luo C, Yang H, Tang C, Yao G, Kong L, He H, Zhou Y. Kaempferol alleviates insulin resistance via hepatic IKK/NF-kappaB signal in type 2 diabetic rats. Int Immunopharmacol 2015; 28: 744-750
• 21 Kim SH, Park JG, Lee J, Yang WS, Park GW, Kim HG, Yi YS, Baek KS, Sung NY, Hossen MJ, Lee MN, Kim JH, Cho JY. The dietary flavonoid kaempferol mediates anti-inflammatory responses via the Src, Syk, IRAK1, and IRAK4 molecular targets. Mediators Inflamm 2015; 2015: 9041-9042
• 22 Ribeiro RM, Pinheiro Neto VF, Ribeiro KS, Vieira DA, Abreu IC, Silva Sdo N, Cartágenes Mdo S, Freire SM, Borges AC, Borges MO. Antihypertensive effect of Syzygium cumini in spontaneously hypertensive rats. Evid Based Complement Alternat Med 2014; 2014: 605452
• 23 Sreelakshmi V, Abraham A. Anthraquinones and flavonoids of Cassia tora leaves ameliorate sodium selenite induced cataractogenesis in neonatal rats. Food Funct 2016; 7: 1087-1095
• 24 Lima-Neto LG, Hirata RD, Luchessi AD, Silbiger VN, Cavichioli D, Dos Santos ES, Sousa AG, Sprovieri SR, De Sousa Junior EB, Dos Santos FC, Colombo S, Hirata MH. Chlamydophila pneumonia and increased TLR4 gene expression in leukocytes are associated with acute myocardial infarction. J Biol Regul Homeost Agents 2014; 28: 449-460