Anti-inflammatory Effect of Apigenin Obtained by Portulaca oleracea L in Male Mice
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Abstract
This study aimed to evaluate the potential anti-inflammatory effects of apigenin, obtained from Portulaca oleracea L., using a male mouse model. A total of 56 healthy BLAB/c albino male mice (Mus musculus) were used in two experiments. In the first experiment, the xylene-induced ear edema, 28 male mice were randomly divided into four groups (n=7). The negative control group received distilled water, while the positive control, apigenin-treated, and indomethacin-treated groups were exposed to xylene (0.03 mL applied to the anterior and posterior surface of the right ear lobe) to induce inflammation. Subsequently, the apigenin-treated group received orally 50 mg/kg BW apigenin, and the indomethacin-treated group received orally 0.36 mg/kg BW indomethacin. Ear weight difference was calculated as an indicator of anti-inflammatory. For the second experiment, the carrageenan-induced paw edema, a similar experimental design was followed, but carrageenan (50 mg/kg BW of 1% solution) was administered intra-dermally in the right hindpaws. Paw skin thickness difference and differential white blood cells (WBCs) count, along with the quantification of prostaglandin E-2 (PGE-2) and interleukin-6 (IL-6) in serum samples, were used as indicators of anti-inflammatory. Results showed that xylene exposure led to a significant ear weight increase, indicative of inflammation. Conversely, the apigenin-treated group demonstrated a reduction in ear weight compared to the positive control group. Similarly, carrageenan administration resulted in a substantial increase in paw skin thickness and elevated levels of WBCs count, PGE-2, and IL-6. Apigenin treatment significantly mitigated these inflammatory markers, outperforming indomethacin in PGE-2 and IL-6. This study provides evidence supporting the potential of P. oleracea-derived apigenin as an effective anti-inflammatory agent, showing comparable or better efficacy than indomethacin.
Received : 24 January 2024
Revised : 12 February 2024
Accepted : 03 April 2024
Published : 28 June 2024
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Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018;9(6):7204. https://doi.org/10.18632/oncotarget.23208
Sugimoto MA, Vago JP, Perretti M, Teixeira MM. Mediators of the resolution of the inflammatory response. Trends Immunol. 2019;40(3):212-227. https://doi.org/10.1016/j.it.2019.01.007
Gayathri B, Manjula N, Vinaykumar KS, Lakshmi BS, Balakrishnan A. Pure compound from Boswellia serrata extract exhibits anti-inflammatory property in human PBMCs and mouse macrophages through inhibition of TNFα, IL-1β, NO and MAP kinases. Int Immunopharmacol. 2007;7(4):473-482. https://doi.org/10.1016/j.intimp.2006.12.003
Germolec DR, Shipkowski KA, Frawley RP, Evans E. Markers of inflammation. In: DeWitt J, Rockwell C, Bowman C, editors. Immunotoxicity testing. Methods in Molecular Biology, vol 1803. New York, NY: Humana Press; 2018. p. 89-103. https://doi.org/10.1007/978-1-4939-8549-4_5
Allahmoradi E, Taghiloo S, Omrani-Nava V, Shobeir SS, Tehrani M, Ebrahimzadeh MA, et al. Anti-inflammatory effects of the Portulaca oleracea hydroalcholic extract on human peripheral blood mononuclear cells. Med J Islam Repub Iran. 2018;32(1):80. https://doi.org/10.14196/mjiri.32.80
Kim HP, Son KH, Chang HW, Kang SS. Anti-inflammatory plant flavonoids and cellular action mechanisms. J Pharmacol Sci. 2004;96(3):229–245. https://doi.org/10.1254/jphs.CRJ04003X
Pirkulashvili N, Tsiklauri N, Nebieridze M, Tsagareli MG. Antinociceptive tolerance to NSAIDs in the agranular insular cortex is mediated by opioid mechanism. J Pain Res. 2017;10:1561. https://doi.org/10.2147/JPR.S138360
Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E. Opioids for chronic non-cancer pain: a meta-analysis of effectiveness and side effects. Can Med Ass J. 2006;174(11):1589–1594. https://doi.org/10.1503/cmaj.051528
Smith TJ. Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases? Pharmacol Rev. 2010;62(2):199-236. https://doi.org/10.1124/pr.109.002469
Zhou YX, Xin HL, Rahman K, Wang SJ, Peng C, Zhang H. Portulaca oleracea L.: a review of phytochemistry and pharmacological effects. Biomed Res Int. 2015;2015:925631. https://doi.org/10.1155/2015/925631
Srivastava R, Srivastava V, Singh A. Multipurpose benefits of an underexplored species Purslane (Portulaca oleracea L.): A critical review. Environ Manage. 2023;72(2):309-320. https://doi.org/10.1007/s00267-021-01456-z
Ahmad R, Ahmad N, Naqvi AA, Shehzad A, Al-Ghamdi MS. Role of traditional Islamic and Arabic plants in cancer therapy. J Tradit Complement Med. 2017;7(2):195-204. https://doi.org/10.1016/j.jtcme.2016.05.002
Syed S, Fatima N, Kabeer G. Portulaca oleracea L.: a mini review on phytochemistry and phramacology. Int J Biol Biotechnol. 2016;13(4):637-641.
Di C, Jun Y, Ting L, Hai Z, Rao L. Research and application of Portulaca oleracea in pharmaceutical area. Chin Herb Med. 2019;11(2):150-159. https://doi.org/10.1016/j.chmed.2019.04.002
Jiang Y, Wang X, Xu Z, Wang L, Zhou J, Yu Y, et al. Antibacterial and antidiarrheal activities of Houttuynia cordata Thunb. and Portulaca oleracea L. extracts against Enterotoxigenic Escherichia coli. 10.2139/ssrn.3924360
Petropoulos S, Karkanis A, Martins N, Ferreira IC. Phytochemical composition and bioactive compounds of common purslane (Portulaca oleracea L.) as affected by crop management practices. Trends Food Sci Technol. 2016;55:1-10. https://doi.org/10.1016/j.tifs.2016.06.010
Al-Okaily BN. Role of Flavonoinds From Nigella sativum seeds in Decreasing the Effect of Hydrogen Peroxide on ECG in Adult Male Rabbits. Iraqi J Vet Med. 2009;33(1):141-148. https://doi.org/10.30539/iraqijvm.v33i1.727
Khalil LW, Alol LH, Obead AI. Effect of crude polyphenol extracted from black olive fruit (olea europae) on some physiological and immunological parameters in Males Rats Treated with Hydrogen Peroxide. Iraqi J Vet Med. 2013;37(1):83-89. https://doi.org/10.30539/iraqijvm.v37i1.337
Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci. 2016;5:e47. https://doi.org/10.1017/jns.2016.41
Rakha A, Umar N, Rabail R, Butt MS, Kieliszek M, Hassoun A, et al. Anti-inflammatory and anti-allergic potential of dietary flavonoids: A review. Biomed Pharmacother. 2022;156:113945. https://doi.org/10.1016/j.biopha.2022.113945
Taqa GA, Sultan ON. Physiological and histological effects of apigenin and luteolin on Cytarabine injected rats. Baghdad Sci J. 2023.https://doi.org/10.21123/bsj.2023.7000
Khudiar KK, Ahmad AK. Protective effect of flavonoids extracted from parsley (Petroselinum sativum L.) leaves on liver function in male rats exposed to cadmium chloride. Iraqi J. Biotech. 2012;11(1):90 –108.
Kim CH, Park PB, Choe SR, Kimz TH, Kim TH, et al. Anti-oxidative and Anti-infammatory Effects of Portulaca oleracea on the LPS-stimulated AGS Cells. Korean J. Orient. Physiol. Pathol. 2009;23(2):488-493.
Lee AS, Kim JS, Lee YJ, Kang DG, Lee HS. Anti-TNF-alpha activity of Portulaca oleracea in vascular endothelial cells. Int. J. Mol. Sci. 2012;13(5):5628-44. https://doi.org/10.3390/ijms13055628
Yue T, Xiaosa W, Ruirui Q, Wencai S, Hailiang X, Min L. The Effects of Portulaca oleracea on Hypoxia-Induced Pulmonary Edema in Mice. High Alt. Med. Biol. 2015;16(1):43-51. https://doi.org/10.1089/ham.2013.1081
Bai Y, Zang X, Ma J, Xu G. Anti-diabetic efect of Portulaca oleracea L. Polysaccharideandits mechanism in diabetic rats. Int. J. Mol. Sci. 2016;17(8):1201. https://doi.org/10.3390/ijms17081201
Xu L, Ying Z, Wei W, Hao D, Wang H, Zhang W, et al. A novel alkaloid from Portulaca oleracea L. Nat. Prod. Res. 2017;31(8):902-908. https://doi.org/10.1080/14786419.2016.1253081
Nayaka HB, Londonkar RL, Umesh MK, Tukappa A. Antibacterial attributes of apigenin, isolated from Portulaca oleracea L. Int J Bacteriol. 2014;2014:175851. https://doi.org/10.1155/2014/175851
Kashams A, Hamza MA, Abbas IS. Effect of humic and salicylic acids on oil yield and flavonoid glycoside of safflowers (Carthamus tinctorius L.) as medicinal plants grown in Iraq. Int J Pharm Sci Res. 2018;9(5):2100–2104. 10.13040/IJPSR.0975-8232.9(5).2100-04
Alsaraf KM, Mohammad MH, Al-Shammari AM, Abbas IS. Selective cytotoxic effect of Plantago lanceolata L. against breast cancer cells. J Egyp Nat Can Inst. 2019;31(1):10. https://doi.org/10.1186/s43046-019-0010-3
Hosseinzadeh H, Younesi HM. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol. 2002;2:7. https://doi.org/10.1186/1471-2210-2-7
Borthakur A, Bhattacharyya S, Dudeja PK, Tobacman JK. Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2007;292(3):G829-G838. https://doi.org/10.1152/ajpgi.00380.2006
Mossa ATH, Ibrahim FM, Mohafrash SM, Abou Baker DH, El Gengaihi S. Protective effect of ethanolic extract of grape pomace against the adverse effects of cypermethrin on weanling female rats. Evid Based Complement Alternat Med. 2015. https://doi.org/10.1155/2015/381919
Coles EH. Veterinary clinical pathology. 2nd ed. WB Saunders; 1974.
El Shoubaky GAE, Abdel-Daim MM, Mansour MH, Salem EA. Isolation and Identification of a Flavone Apigenin from Marine Red Alga Acanthophora spicifera with Antinociceptive and Anti-Inflammatory Activities. J Exp Neurosci. 2016;10:21-29. https://doi.org/10.4137/JEN.S25096
Sadraei H, Asghari G, Khanabadi M, Minaiyan M. Anti-inflammatory effect of apigenin and hydroalcoholic extract of Dracocephalum kotschyi on acetic acid-induced colitis in rats. Res Pharm Sci. 2017;12(4):322. https://doi.org/10.4103/1735-5362.212050
Mondal A, Dikshit H, Mohan L, Mishra H, Kumar M, Ahmad M, et al. Evaluation of Analgesic Effect of Apigenin in Rodent. Int J Pharm Sci Rev Res. 2022;72(1):155-159. https://doi.org/10.47583/ijpsrr.2022.v72i01.021
Al-Taai IAA. Analgesic and Anti-inflammatory Effects of Nicotine. Master thesis; 2011. p.43-44.
Meyer VR. Practical High-Performance Liquid Chromatography, 5th edition. United Kingdom: John Wiley & Sons; 2010. https://doi.org/10.1002/9780470688427
Mushtaq Z, Sadeer NB, Hussain M, Mahwish, Alsagaby SA, Imran M, et al. Therapeutical properties of apigenin: a review on the experimental evidence and basic mechanisms. Int J Food Proper. 2023;26(1):1914-1939. https://doi.org/10.1080/10942912.2023.2236329
Kafi LA, AL–Zobahi YZA. Effect of sweet almond suspension as anti-inflammatory in experimental infected mice with arthritis: AL–Zobahi YZA. Iraqi J Vet Med. 2012;36(2):98-105. https://doi.org/10.30539/iraqijvm.v36i2.453
Hongzhi D, Xiaoying H, Yujie G, Le C, Yuhan M, Dahui L, et al. Classic mechanisms and experimental models for the anti-inflammatory effect of traditional Chinese medicine. Anim Models Exp Med. 2022; 5: 108-119. https://doi.org/10.1002/ame2.12224
Eddouks M, Chattopadhyay D, Zeggwagh NA. Animal models as tools to investigate antidiabetic and anti-inflammatory plants. Evid.-Based Complement. Altern. Med. 2012;2012: 142087. https://doi.org/10.1155/2012/142087
Nicholas C, Batra S, Vargo MA, Voss OH, Gavrilin MA, Wewers MD, et al. Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-κB through the suppression of p65 phosphorylation. J Immunol. 2007;179(10):7121-717. https://doi.org/10.4049/jimmunol.179.10.7121
Jeong GS, Lee SH, Jeong SN, Kim YC, Kim EC. Anti-inflammatory effects of apigenin on nicotine-and lipopolysaccharide-stimulated human periodontal ligament cells via heme oxygenase-1. Int Immunopharmacol. 2009;9(12):1374-80. https://doi.org/10.1016/j.intimp.2009.08.015
Shukla S, Gupta S. Apigenin: a promising molecule for cancer prevention. Pharm Res. 2010;27:962-978. https://doi.org/10.1007/s11095-010-0089-7
Morris CJ. Carrageenan-Induced Paw Edema in the Rat and Mouse. In: Winyard PG, Willoughby DA, editors. Methods in Molecular Biology. Volume 225: Inflammation Protocols. Totowa, NJ: Humana Press Inc.; 2013. p. 115-121. https://doi.org/10.1385/1-59259-374-7:115
Patil KR, Mahajan UB, Unger BS, Goyal SN, Belemkar S, Surana SJ, et al. Animal models of inflammation for screening of anti-inflammatory drugs: implications for the discovery and development of phytopharmaceuticals. Int J Mol Sci. 2019;20(18):4367. https://doi.org/10.3390/ijms20184367
Winter CA, Risley EA, Nuss GW. Carrageenin-Induced Edema in Hind Paw of the Rat as an Assay for Antiinflammatory Drugs. Exp. Boil. Med. 1962;111:544–554. https://doi.org/10.3181/00379727-111-27849
Vinegar R, Schreiber W, Hugo R. Biphasic development of carrageenin edema in rats. J Pharm Experi. Therap. 1969;166(1):96–103, 1969.
Abd-Allah AAM, El-Deen NAMN, Mohamed WAM, Naguib FM. Mast cells and pro-inflammatory cytokines roles in assessment of grape seeds extract anti-inflammatory activity in rat model of carrageenan-induced paw edema. Iran J Basic Med Sci. 2018;21(1):97. 10.22038/IJBMS.2017.25067.6219
Suou K, Taniguchi F, Tagashira Y, Kiyama T, Terakawa N, Harada T. Apigenin inhibits tumor necrosis factor α–induced cell proliferation and prostaglandin E2 synthesis by inactivating NFκB in endometriotic stromal cells. Fertil Steril. 2011;95(4):1518-1521. https://doi.org/10.1016/j.fertnstert.2010.09.046
Van LS, Miteva K, Tschöpe C. Crosstalk between fibroblasts and inflammatory cells. Cardiovasc Res. 2014; 102:258–269. https://doi.org/10.1093/cvr/cvu062
Hirano T, Higa S, Arimitsu J, Naka T, Shima Y, Ohshima S, et al. Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by ActivatedHuman basophils. Inte Arch Aller Immunol. 2004;134(2):135-140. https://doi.org/10.1159/000078498
Park C-H, Min S-Y, Yu H-W, Kim K, Kim S, Lee H-J, Kim J-H, Park Y-J. Effects of Apigenin on RBL-2H3, RAW264.7, and HaCaT Cells: Anti-Allergic, Anti-Inflammatory, and Skin-Protective Activities. Int. J. Mol. Sci. 2020, 21: 4620. https://doi.org/10.3390/ijms21134620
Márquez-Flores YK, Villegas, I., Cárdeno A, Rosillo MÁ, Alarcón-de-la-Lastra C. Apigenin supplementation protects the development of dextran sulfate sodium-induced murine experimental colitis by inhibiting canonical and non-canonical inflammasome signaling pathways. J Nutrit Biochem. 2016;30:143–152. https://doi.org/10.1016/j.jnutbio.2015.12.002
Li H, Zhang H, Zhao H. Apigenin attenuates inflammatory response in allergic rhinitis mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Environm Toxicol. 2023;38(2):253-265. https://doi.org/10.1002/tox.23699
Ganjare AB, Nirmal SA, Patil AN. Use of apigenin from Cordia dichotoma in the treatment of colitis. Fitoterapia. 2011;82(7):1052-1056. https://doi.org/10.1016/j.fitote.2011.06.008
Cardenas H, Arango D, Nicholas C, Duarte S, Nuovo GJ, He W, Voss OH, Gonzalez-Mejia ME, Guttridge DC, Grotewold E, Doseff AI. Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-κB Activity, Halting Leukocyte Infiltration and Restoring Normal Metabolic Function. Int J Mol Sci. 2016;17(3):323. https://doi.org/10.3390/ijms17030323
Woo ER, Pokharel YR, Yang JW, Lee SY, Kang KW. Inhibition of nuclear factor-κb activation by 2′,8′′-biapigenin. Biol. Pharm. Bull. 2006;29:976–980. https://doi.org/10.1248/bpb.29.976
Kowalski J, Samojedny A, Paul M, Pietsz G, Wilczok T. Effect of apigenin, kaempferol and resveratrol on the expression of interleukin-1b and tumor necrosis factor-α genes in j774.2 macrophages. Pharmacol. Rep. 2005;57:390–394.
Schmidt-Arras D, Rose-John S. IL-6 pathway in the liver: from physiopathology to therapy. J Hepatol. 2016;64(6): 1403-1415. https://doi.org/10.1016/j.jhep.2016.02.004
Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986-1000. https://doi.org/10.1161/ATVBAHA.110.207449
Li KC, Ho YL, Hsieh WT, Huang SS, Chang YS, Huang GJ. Apigenin-7-Glycoside prevents LPS-induced acute lung injury via downregulation of oxidative enzyme expression and protein activation through inhibition of MAPK phosphorylation. Int. J. Mol. Sci. 2015,16(1):1736–1754.https://doi.org/10.3390/ijms16011736
Alol LA, Al-Mzaien KA, Hussein SM. The Promising Anticancer Efficacy of Parsley Seeds Flavonoid (Apigenin) in Induced Mammary Adenocarcinoma (AMN3) Mice. J Physiol Biomed Sci. 2012;25(1):5-12.
Alol LH, Al-Mzaein KA, Hussein SHM. Anticancer effect of flavonoid (apigenin) extracted from Parsley (Petroselineum sativum) seeds in cancer cells lines. Iraqi J Cancer. 2009; 2(1).