In Vitro Antidiabetic, Antiinflammatory, Cytotoxic, Antioxidant and Antimicrobial Activities of Pomegranate (Punica granatum L.) Peel

Year 2019, Volume: 17 Issue: 1, 61 - 71, 26.03.2019

Tuğba Demir , Özlem Akpınar , Haki Kara , Hüseyin Güngör

https://doi.org/10.24323/akademik-gida.544647

Cited By: 13

Abstract

In this study, antioxidant, antimicrobial,
antidiabetic, antiinflammatory and cytotoxic properties of the pomegranate (Punica granatum L.) peel were
investigated. The composition of the phenolic compounds of the pomegranate peel
extract (33%, 78°C, 113 min) was determined and it was found to contain high amounts
of punigalagin, caffeic acid and epicatechin. At the same time, the extract was
found to have high antioxidant capacity.  It showed antimicrobial activity against
selected microorganisms (Staphylococcus aureus, Enterococcus
faecalis, Escherichia
coli, Aspergillus flavus and Aspergillus niger) and its
highest microbial resistance was found to be against S. aureus (21 mm; 1.87 mg extract
/mL). It inhibited α-amylase and α-glucosidase enzymes and showed the antidiabetic
property. At the same time, the extract was able to inhibit xanthine oxidase
and lipoxygenase enzymes that were responsible for the inflammation and its cytotoxic
activity on breast and bone cancer cells were also observed. It was concluded
that pomegranate peel extracts could be used in food and non-food applications due
to its biological activities.

Keywords

Pomegranate peel, Antimicrobial, Antidiabetic, Antiinflammatory, Cytotoxic

Nar (Punica granatum L.) Kabuğunun İn Vitro Antidiyabetik, Antienflamatuar, Sitotoksik, Antioksidan ve Antimikrobiyal Aktivitesi

Abstract

Bu çalışmada nar (Punica granatum L.) kabuğunun sağlık
açısından önemli antioksidan, antimikrobiyal, antidiyabetik, antienflamatuar ve
sitotoksik özellikleri araştırılmıştır. Nar kabukları (%33 etanol
konsantrasyonu, 78°C, 113 dakika) ekstrakte edilerek fenolik
bileşiklerinin kompozisyonu belirlenmiş, yüksek oranda punigalajin, kafeik asit ve epikateşin içerdiği ve
yüksek antioksidan kapasiteye sahip olduğu tespit edilmiştir. Elde edilen
ekstrakt aynı zamanda, seçilen mikroorganizmalara (Staphylococcus aureus, Enterococcus
faecalis, Escherichia
coli, Aspergillus flavus ve Aspergillus niger) karşı antimikrobiyal
etki göstermiş ve en fazla mikrobiyal direnci S. aureus’a
(21 mm; 1.87 mg ekstrakt/mL) karşı olduğu bulunmuştur. Ekstrakt  α-amilaz ve α-glukozidaz
enzimlerini inhibe etmiş ve antidiyabetik özellik göstermiştir. Aynı zamanda
ekstraktın enflamasyondan sorumlu ksantin oksidaz ve lipoksigenaz enzimlerini
de inhibe edebildiği ve meme ve kemik kanseri
hücreleri üzerinde sitotoksik aktiviteye sahip olduğu da gözlenmiştir. Nar
kabuğu ekstraktının belirlenen biyolojik aktiviteleri ile gıda ve gıda dışı
uygulamalarda kullanılabileceği sonucuna varılmıştır.

Keywords

Nar kabuğu, Antimikrobiyal, Antidiyabetik, Antienflamatuar, Sitotoksik

References

• [1] Bayram, E., Kırcı, S., Tansı, S., Yılmaz, G., Arabacı, O., Kızıl, S., Telci, İ. (2010). Tıbbi ve aromatik bitkiler üretiminin arttırılması olanakları, Türkiye Ziraat Mühendisliği VII. Teknik Kongresi, Ankara.
• [2] Jaiswal, V., DerMarderosian, A., Porter, J.R. (2010). Anthocyanins and polyphenol oxidase from dried arils of pomegranate (Punica granatum L.). Food Chemistry, 118(1), 11-16.
• [3] T.C. Başbakanlık Türkiye İstatistik Kurumu https://biruni.tuik.gov.tr/bitkiselapp/bitkisel.zul
• [4] Samaranayaka, A.G.P., Li-Chan, E.C.Y. (2011). Food-derived peptidic antioxidants: A review of their production, assessment, and potential applications. Journal of Functional Food, 3(4), 229-254.
• [5] Yusof, H., Radzı, N.A.S.M., Rıchard, R.L. (2018). Qualitative phytochemical analysis and antimicrobial activity of piper sarmentosum leaves extract against selected pathogens. Malaysian Journal of Health Sciences, 17.1.
• [6] Wanasundara, U.N., Shahidi, F. (1998). Antioxidant and prooxidant activity of green tea extracts in marine oils. Food Chemistry, 63(3), 335-342.
• [7] Naczk, M., Shahidi, F. (2006). Phenolics in cereals, fruits and vegetables: Occurrence, extraction and analysis. Journal of Pharmaceutical and Biomedical Analysis, 41(5), 1523-1542.
• [8] Friedman, M. (2007). Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas. Molecular Nutrition and Food Research, 51(1): 116-134.
• [9] Sharmila, G., Bhat, F.A., Arunkumar, R., Elumalai, P., Singh, P.R., Senthilkumar, K., Arunakaran, J. (2014). Chemopreventive effect of quercetin, a natural dietary flavonoid on prostate cancer in in vivo model. Clinical Nutrition 33(4), 718-726.
• [10] Skowyra, M., Falguera, V., Gallego, G., Peiro, S., Almajano, M.P. (2014). Antioxidant properties of aqueous and ethanolic extracts of tara (Caesalpinia spinosa) pods in vitro and in model food emulsions. Journal of the Science of Food and Agriculture, 94(5), 911-918.
• [11] Mai, T.T., Thu N. N., Tien P.G., Van Chuyen, N. (2007). Alpha-glucosidase inhibitory and antioxidant activities of Vietnamase edible plants and their relationships with polyphenol contents. Journal of Nutritional Science and Vitaminology, 53(3), 267-276.
• [12] Tomy M. J., Sharanya C. S., Dileep K. V., Prasanth S., Sabu A., Sadasivan C., Haridas M. (2014). Derivatives form better lipoxygenase inhibitors than piperine: in vitro and in silico study. Chemical Biology and Drug Design, 85(6), 715-721.
• [13] Kulkarni, S.G., Vijayanand, P. (2010). Effect of extraction conditions on the quality characteristics of pectin from passion fruit peel (Passiflora edulis f. flavicarpa L.). Food Science and Technology, 43(7), 1026-1031.
• [14] Wang, R., Ding, Y., Liu, R., Xiang, L., Du, L. (2010). Pomegranate: Constituents, bioactivities and pharmacokinetics. Fruit, Vegetable and Cereal Science and Biotechnology, 4(2), 77-87.
• [15] Prakash, C.V.S., Prakash, I. (2011). Bioactive chemical constituents from pomegranate (Punica granatum) juice, seed and peel-a review. International Journal of Research in Chemistry and Environment, 1(1), 1-18.
• [16] Amyrgialaki, E., Makris, D.P., Mauromoustakos, A., Kefalas, P. (2014). Optimisation of the extraction of pomegranate (Punica granatum) husk phenolics using water/ethanol solvent systems and response surface methodology. Industrial Crops and Products, 59, 216-222.
• [17] Nahar, P.P., Driscoll, M.V., Li, L., Slitt, A.L., Seeram, N.P. (2014). Phenolic mediated anti-inflammatory properties of a maple syrup extract in RAW 264.7 murine macrophages. Journal of Functional Foods, 6, 126-136.
• [18] Li, Y., Guo, C., Jijun, Y., Wei, J., Xu, J., Cheng, S. (2006). Evaluation of antioxidant properties of pomegranate peel extract in comparison with pomegranate pulp extract. Food Chemistry, 96(2), 254-260.
• [19] Yılmaz, B., Usta, C., (2011). Narın (Punica granatum) terapötik etkileri. Türk Aile Hekimliği Dergisi, 14(3), 146-153.
• [20] Mphahlele, R.R., Fawole, O.A., Makunga, N.P., Opara, U.L. (2016). Effect of drying on the bioactive compounds, antioxidant, antibacterial and antityrosinase activities of pomegranate peel. BMC complementary and alternative medicine, 16(1), 143.
• [21] Malviya, S., Jha, A., Hettiarachchy, N. (2014). Antioxidant and antibacterial potential of pomegranate peel extracts. Journal of Food Science and Technology, 51(12), 4132-4137.
• [22] Marchi, L.B., Monteiro, A.R., Mikcha, J.M., Santos, A.R., Chinellato, M.M., Marques, D.R., Costa, S.C. (2015). Evaluation of antioxidant and antimicrobial capacity of pomegranate peel extract (Punica granatum L.) under different drying temperatures. Chemical Engineering Transactions, 44, 121-126.
• [23] Türkyılmaz, M., Tağı, Ş., Özkan, M. (2017). Effects of extraction solvents on polyphenol contents, antioxidant and antibacterial activities of pomegranate parts. Academic Food Journal/Akademik Gıda, 15(2), 109-118.
• [24] Al-Zoreky, N.S. (2009). Antimicrobial activity of pomegranate (Punica granatum L.) fruit peels. International Journal of Food Microbiology, 134(3), 244-248.
• [25] Jain, V., Viswanatha, G.L., Manohar, D., Shivaprasad, H.N. (2012). Isolation of antidiabetic principle from fruit rinds of Punica granatum. Evidence Based Complementary Alternative Medicine, 147202, 1-11.
• [26] Adams, L.S., Seeram, N.P., Aggarwal, B.B., Takada, Y., Sand, D., Heber, D. (2006). Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells. Journal of Agricultural and Food Chemistry, 54, 980–985.
• [27] Seeram, N.P., Schulman, R.N., Heber, D. (2006). Pomegranates: Ancient Roots to Modern Medicine. Taylor and Francis CRC Press, Boca Raton, FL, USA.
• [28] Ackland, M.L., VandeWaarsenburg, S., Jones, R. (2005). Synergistic antiproliferative action of the flavonols quercetin and kaempferol in cultured human cancer cell lines. International Journal of Experimental and Clinical Pathophysiology and Drug Research, 19, 69–76.
• [29] Horinaka, M., Yoshida, T., Shiraishi, T., Nakata, S., Wakada, M., Nakanishi, R., Nishino, H., Matsui, H., Sakai, T. (2005). Luteolin induces apoptosis via death receptor 5 upregulation in human malignant tumor cells. Oncogene, 24(48), 7180-7189.
• [30] Brusselmans, K., Vrolix, R., Verhoeven, G., Swinnen, J.V. (2005). Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. Journal of Biological Chemistry, 280(7), 5636–5645.
• [31] Hou, D.X., Ose, T., Lin, S., Harazoro, K., Imamura, I., Kubo, M., Uto, T., Terahara, N., Yoshimoto, M., Fujii, M. (2003). Anthocyanidins induce apoptosis in human promyelocytic leukemia cells: Structure-activity relationship and mechanisms involved. International Journal of Oncology, 23(3), 705-712.
• [32] Lansky, E.P., Harrison, G., Froom, P., Jiang, W. G. (2005). Pomegranate (Punica granatum) pure chemicals show possible synergistic inhibition of human PC-3 prostate cancer cell invasion across matrigel. Investigational New Drugs, 23, 121-2.
• [33] Demir, T., Akpınar, Ö., Kara, H., Güngör, H. (2019). Nar kabuğundan antimikrobiyal ve antioksidan aktiviteye sahip fenolik bileşiklerin ekstraksiyon koşullarının optimizasyonu. Gıda (kabul edildi, basımda)
• [34] Cai, Y., Luo, Q., Sun, M., Corke, H. (2014). Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sciences, 74(17), 2157-2184.
• [35] Maisuthisakul, P., Suttajit, M., Pongsawatmanit, R. (2007). Assessment of phenolic content and free radical-scavenging capacityof some Thai indigenous plants. Food Chemistry, 100(4):1409-1418.
• [36] Singleton, V.L., Rossi, J.A. (1965). Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. American Journal of Enology and Viticuture, 16, 144-158.
• [37] Zhishen, J., Mengcheng, T., Jianming, W. (1999). The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chemistry, 64(4), 555-559.
• [38] Ávila-Reyes, J. A., Almaraz-Abarca, N., Chaidez-Ayala, A. I., Ramírez-Noya, D., Delgado-Alvarado, E. A., Torres-Ricario, R., Alanís-Bañuelos, R.E. (2018). Foliar phenolic compounds of ten wild species of Verbenacea as antioxidants and specific chemomarkers. Brazilian Journal of Biology, 78(1), 98-107.
• [39] Brand-Williams, W., Cuvelier, M., Berset, C. (1995). Use of free radical method to evaluate antioxidant activity. Food Science and Technology, 28, 25–30.
• [40] Benzie, I.F.F., Strain, J.J. (1996). The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay. Analytical Biochemistry, 239, 70–76.
• [41] Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M., Rice-Evans, C. (1999). Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biology and Medicine, 26, 1231–1237.
• [42] Ebrahimabadi, A.H., Bidgoli, Z., Mazoochi, A., Kashi, F.J., Batooli, H. (2010). Essential oil composition, antioxidant and antimicrobial activity of the leaves and flowers of Chaerophyllum macropodum Boiss. Food Control, 21, 1173-1178.
• [43] Oskay, M., Aktaş, K., Sarı, D., Azeri, C. (2007). Asphodelus aestivus (Liliaceae)'un antimikrobiyal etkisinin çukur ve disk diffüzyon yöntemiyle karşılaştırmalı olarak belirlenmesi. Ekoloji Dergisi, 16, 62-65.
• [44] Worthington, V. (1993) Alpha amylase. In: Worthington V, ed. Worthington Enzyme Manual; enzymes and related biochemicals. Lakewood, NJ: Worthington Biochemical Company, 36-41.
• [45] Miller, G.L. (1959). Use of dinitrosalicylic acid reagent for determination of reducing sugar. Analytical Chemistry, 31, 426-428.
• [46] Alaba, C.S.M., Chichioco-Hernandez, C.L. (2014). 15–Lipoxygenase inhibition of Commelina benghalensis, Tradescantia fluminensis, Tradescantia zebrina. Asian Pacific Journal of Tropical Biomedicine, 4 (3), 184-188.
• [47] Nessa, F., Ismail, Z., Mohamed, N. (2010). Xanthine oxidase inhibitory activities of extracts and flavonoids of the leaves of Blumea balsamifera. Pharmaceutical Biology, 48(12), 1405-1412.
• [48] Betancur-Galvis, L.A., Morales, G.E., Forero, J.E., Roldan, J. (2002). Cytotoxic and antiviral activities of Colombian medicinal plant extracts of the Euphorbia genus. Memorias do Instituto Oswaldo Cruz, 97(4), 541-546.
• [49] Horakova, K., Sovcikova, A., Seemannova, Z., Syrova, D., Busanyova, K., Drobna, Z., Ferencik, M. (2001). Detection of drug-induced, superoxide-mediated cell damage and its prevention by antioxidants. Free Radical Biology and Medicine, 30(6), 650-664.
• [50] Pinelo, M., Del Fabbro, P., Manzocco, L., Nunez, M. J., Nicoli, M.C. (2005). Optimization of continuous phenol extraction from Vitis vinifera byproducts. Food Chemistry, 92(1), 109-117.
• [51] Singh, R.P., Chidambara-Murthy, K.N., Jayaprakasha, G.K. (2002). Studies on the antioxidant activity of pomegranate (Punica granatum) peel and seed extracts using in vitro models. Journal of Agricultural and Food Chemistry, 50 (1), 81-86.
• [52] Ibrahium, M.I. (2010). Efficiency of pomegranate peel extract as antimicrobial, antioxidant and protective agents. World Journal of Agricultural Sciences, 6 (4), 338-344.
• [53] Gil, M.I., Tomas-Barberan, F.A., Hess-Pierce, B., Holcroft, D.M., Kader, A.A, (2000). Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. Journal of Agricultural and Food Chemistry, 48(10), 4581-4589.
• [54] MacDonald-Wicks, L.K., Wood, L.G., Garg, M.L. (2006). Methodology for the determination of biological antioxidant capacity in vitro: A review. Journal of the Science of Food and Agriculture, 86(13), 2046-2056.
• [55] Mushtaq, M., Sultana, B., Anwar, F., Adnan, A., Rizvi, S.S. (2015). Enzyme-assisted supercritical fluid extraction of phenolic antioxidants from pomegranate peel. The Journal of Supercritical Fluids, 104, 122-131.
• [56] Fawole, O.A., Makunga, N.P., Opara, U.L. (2012). Antibacterial, antioxidant and tyrosinase-inhibition activities of pomegranate fruit peel methanolic extract. BMC Complementary and Alternative Medicine, 12(1), 200.
• [57] Farag, M.A., Al-Mahdy, D.A., Salah El Dine, R., Fahmy, S., Yassin, A., Porzel, A., Brandt, W. (2015). Structure activity relationships of antimicrobial gallic acid derivatives from pomegranate and acacia fruit extracts against potato bacterial wilt pathogen. Chemistry & Biodiversity, 12(6), 955-962.
• [58] Gullon, B., Pintado, M.E., Pérez-Álvarez, J.A., Viuda-Martos, M. (2016). Assessment of polyphenolic profile and antibacterial activity of pomegranate peel (Punica granatum) flour obtained from co-product of juice extraction. Food Control, 59, 94-98.
• [59] Dik, B. (2013). Metabolik sendromun tedavisi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 8(3), 259-269.
• [60] Jung, M., Park, M., Lee, H.C., Kang, Y.H., Kang, E.S., Kim, S.K. (2006). Antidiabetic agents from medicinal plants. Current Medicinal Chemistry, 13 (10), 1203-1218.
• [61] Longo, R. (2010). Diabetes under control: Understanding oral antidiabetic agents. The American Journal of Nursing, 110(2), 49-52.
• [62] Çam, M., İçyer, N.C. (2015). Phenolics of pomegranate peels: extraction optimization by central composite design and alpha glucosidase inhibition potentials. Journal of Food Science and Technology, 52(3), 1489-1497.
• [63] Šavikin, K., Živković, J., Alimpić, A., Zdunić, G., Janković, T., Duletić-Laušević, S., Menković, N. (2018). Activity guided fractionation of pomegranate extract and its antioxidant, antidiabetic and antineurodegenerative properties. Industrial Crops and Products, 113, 142-149.
• [64] Kam, A., Li, K.M., Razmovski‐Naumovski, V., Nammi, S., Shi, J., Chan, K., Li, G.Q. (2013). A Comparative Study on the Inhibitory Effects of Different Parts and Chemical Constituents of Pomegranate on α‐Amylase and α‐Glucosidase. Phytotherapy Research, 27(11), 1614-1620.
• [65] Hasenah, P., Houghton, J., Soumyanath, A. (2006). α-Amylase inhibitory activity of some Malaysian plants used to treat diabetes; with particular reference to Phyllanthus amarus. Journal of Ethnopharmacology 10(3), 449-455.
• [66] Trouillas, P., Calliste, C.A., Allais, D.P., Simon, A., Marfak, A., Delage, C., Duroux, J.L. (2003). Antioxidant, anti-inflammatory and antiproliferative properties of sixteen water plant extracts used in the Limousin countryside as herbal teas. Food Chemistry, 80(3), 399-407.
• [67] Onat, T., Emerk, K., Sözmen, E.Y. (2006). İnsan Biyokimyası, Palme Yayıncılık, 21-37s, Ankara.
• [68] Nishino, T., Okamoto, K., Eger, BT., Pai, E.F., Nishino, T. (2008). Mammalian xanthine oxidoreductase–mechanism of transition from xanthine dehydrogenase to xanthine oxidase. The FEBS Journal, 275(13), 3278-3289.
• [69] Çam, M., İçyer, N.C., Erdoğan, F. (2014). Pomegranate peel phenolics: Microencapsulation, storage stability and potential ingredient for functional food development. LWT-Food Science and Technology, 55(1), 117-123.
• [70] Akhtar, S., Ismail, T., Sestili, P., Riaz, M., Ismail, A., Labbe, R.G. (2016). Antioxidant, antimicrobial and urease inhibitory activities of phenolics-rich pomegranate peel hydro-alcoholic extracts. Journal of Food Biochemistry, 40(4), 550-558.
• [71] Tew, K.D., Gate, L. (2001). Glutathione S-transferases as emerging therapeutic targets. Expert Opinion on Therapeutic Targets, 5(4), 477.
• [72] Çağlar, H.O., Süslüer, S.Y., Kavaklı, Ş., Gündüz, C., Ertürk, B., Özkınay, F., Haydaroğlu, A. (2017). Meme kanseri kök hücrelerinde elajik asit ile indüklenmiş mRNA’ların ifadesi ve elajik asidin apoptoz üzerine etkisi. Ege Tıp Dergisi, 56(4), 183-192.
• [73] Hwang, H.J., Park, H.J., Chung, H.J., Min, H.Y., Park, E.J., Hong, J.Y., Lee, S.K. (2005). Inhibitory effects of caffeic acid phenethyl ester on cancer cell metastasis mediated by the down-regulation of matrix metalloproteinase expression in human HT1080 fibrosarcoma cells. Journal of Nutritional Biochemistry, 17(5), 356-362.
• [74] Yang, J.H.H., Hsia, T.C., Kuo, H.M., Chao, P.D., Chou, C.C., Wei, Y.H., Hchung, J.G. (2006). Inhibition of lung cancer cell growth by quercetin glucuronides via G2/M arrest and induction of apoptosis. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 34(1), 296-304.
• [75] Lea, M.A., Xiao, Q., Sadhukhan, A.K., Cottle, S., Wang, Z.Y., Yang, C.S. (1993). Inhibitory effects of tea extracts and (-)-epigallocatechin gallate on DNA synthesis and proliferation of hepatoma and erythroleukemia cells. Cancer letters, 68(2), 231-236.
• [76] Sakarkar, D.M., Deshmukh. V.N. (2011). Ethnopharmacological review of traditional medicinal plants for anticancer activity. International Journal of PharmTech Research, 3(1), 298-308.
• [77] Moradzadeh, M., Roustazadeh, A., Tabarraei, A., Erfanian, S., Sahebkar, A. (2017). Epigallocatechin‐3‐gallate enhances differentiation of acute promyelocytic leukemia cells via inhibition of PML‐RARα and HDAC1. Phytotherapy Research, 3, 1-9.