IN VITRO EVALUATION OF ANTIOXIDANT AND CYTOTOXIC ACTIVITIES ON HUMAN CERVICAL CANCER CELLS IN THREE DIFFERENT PLANT EXTRACTS FROM TURKEY

Year 2023, Issue: 054, 338 - 352, 30.09.2023

Funda Ulusu

https://doi.org/10.59313/jsr-a.1262754

Abstract

The objective of this investigation was to assess the total phenolic and flavonoid content within acetone and water extracts derived from Erica manipuliflora, Ferula communis, and Stevia rebaudiana plants. Additionally, the in vitro antioxidant and cytotoxic effects of these extracts were evaluated using the human cervical cancer (HeLa) cell line as a model. Among the three plant species examined, the highest concentrations of total phenols and flavonoids were found in the acetone extract of E. manipuliflora, measuring 365.29 mg GAE/g DW and 105.42 mg QE/g DW, respectively. Acetone and water extracts of E. manipuliflora showed higher DPPH scavenging activities (IC50: 37.57 and 33.27 µg/mL, respectively) compared to other plants. furthermore, E. manipuliflora acetone extract (IC50: 97.35 µg/mL) exhibited the highest inhibition in the HeLa cell line treated with the extracts, thus being the most effective extract on this cell line. As a result of the analyzes, it has been shown that F. communis and S. rebaudiana and especially E. manipuliflora are important natural antioxidant sources with their strong radical scavenging effects, as well as the anticancer potential of these plants.

Keywords

Erica manipuliflora, Ferula communis, Stevia rebaudiana, Antioxidant, Cytotoxic Activities, Phenolic Content

References

• [1] Khan, T., Ali, M., Khan, A., Nisar, P., Jan, S. A., Afridi, S., Shinwari, Z. K., (2019), Anticancer plants: A review of the active phytochemicals, applications in animal models, and regulatory aspects. Biomolecules, 10, 47.
• [2] Sen, T.,Samanta, S. K., (2015), Medicinal plants, human health and biodiversity: a broad review. Biotechnological applications of biodiversity, 59-110.
• [3] Hasanuzzaman, M., Bhuyan, M. B., Zulfiqar, F., Raza, A., Mohsin, S. M., Mahmud, J. A., Fotopoulos, V., (2020), Reactive oxygen species and antioxidant defense in plants under abiotic stress: Revisiting the crucial role of a universal defense regulator. Antioxidants, 9, 681.
• [4] Allen, S., Britton, J. R., Leonardi-Bee, J. A., (2009), Association between antioxidant vitamins and asthma outcome measures: systematic review and meta-analysis. Thorax, 64, 610-619.
• [5] Myung, S. K., Ju, W., Cho, B., Oh, S. W., Park, S. M., Koo, B. K., Park, B. J., (2013)., Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials. Bmj, 346.
• [6] Saeidnia, S., Abdollahi, M., (2013), Toxicological and pharmacological concerns on oxidative stress and related diseases. Toxicology and applied pharmacology, 273, 442-455.
• [7] Salehi, B., Azzini, E., Zucca, P., Maria Varoni, E., V. Anil Kumar, N., Dini, L., Sharifi-Rad, J., (2020), Plant-derived bioactives and oxidative stress-related disorders: a key trend towards healthy aging and longevity promotion. Applied sciences, 10, 947.
• [8] Fernandes, R. D. P. P., Trindade, M. A., de Melo, M. P., (2018), Natural antioxidants and food applications: healthy perspectives. In Alternative and replacement foods (pp. 31-64). Academic Press.
• [9] Yüksel, A. K., Dikici, E., Yüksel, M., Işik, M., Tozoğlu, F., Köksal, E., (2021), Phytochemicals analysis and some bioactive properties of Erica manipuliflora Salisb.(EMS); Antibacterial, Antiradical and Anti-lipid Peroxidation. Iranian Journal of Pharmaceutical Research: IJPR, 20, 422.
• [10] Kuş, Ç., Taş, M., Küçükaydin, S., Tel-Cayan, G., Duru, M. E., (2019), Chemical analysis and in vitro antioxidant and anticholinesterase activities of essential oils and extracts from different parts of Erica manipuliflora. J. Res. Pharm, 23, 1098-1105.
• [11] Rahali, F. Z., Kefi, S., Bettaieb Rebey, I., Hamdaoui, G., Tabart, J., Kevers, C., Hamrouni Sellami, I., (2019), Phytochemical composition and antioxidant activities of different aerial parts extracts of Ferula communis L. Plant Biosystems-An International Journal Dealing with all Aspects of Plant Biology, 153, 213-221.
• [12] Maggi, F., Papa, F., Dall’Acqua, S., Nicoletti, M., (2016), Chemical analysis of essential oils from different parts of Ferula communis L. growing in central Italy. Natural Product Research, 30, 806-813.
• [13] Monti, M., Pinotti, M., Appendino, G., Dallocchio, F., Bellini, T., Antognoni, F., Bernardi, F., (2007), Characterization of anti-coagulant properties of prenylated coumarin ferulenol. Biochimica et Biophysica Acta (BBA)-General Subjects, 1770, 1437-1440.
• [14] Mamoci, E., Cavoski, I., Andres, M. F., Díaz, C. E., Gonzalez-Coloma, A., (2012), Chemical characterization of the aphid antifeedant extracts from Dittrichia viscosa and Ferula communis. Biochemical Systematics and Ecology, 43, 101-107.
• [15] Maiuolo, J., Musolino, V., Guarnieri, L., Macrì, R., Coppoletta, A. R., Cardamone, A., Mollace, V., (2022), Ferula communis L.(Apiaceae) Root Acetone-Water Extract: Phytochemical Analysis, Cytotoxicity and In Vitro Evaluation of Estrogenic Properties. Plants, 11, 1905.
• [16] Marchi, A., Appendino, G., Pirisi, I., Ballero, M., Loi, M. C., (2003), Genetic differentiation of two distinct chemotypes of Ferula communis (Apiaceae) in Sardinia (Italy). Biochemical Systematics and Ecology, 31, 1397-1408.
• [17] Lemus-Mondaca, R., Vega-Gálvez, A., Zura-Bravo, L., Ah-Hen, K., (2012), Stevia rebaudiana Bertoni, source of a high-potency natural sweetener: A comprehensive review on the biochemical, nutritional and functional aspects. Food chemistry, 132, 1121-1132.
• [18] Zaidan, U. H., Zen, N. I. M., Amran, N. A., Shamsi, S., Abd Gani, S. S., (2019), Biochemical evaluation of phenolic compounds and steviol glycoside from Stevia rebaudiana extracts associated with in vitro antidiabetic potential. Biocatalysis and Agricultural Biotechnology, 18, 101049.
• [19] Hajihashemi, S., Geuns, J. M., (2013), Free radical scavenging activity of steviol glycosides, steviol glucuronide, hydroxytyrosol, metformin, aspirin and leaf extract of Stevia rebaudiana. Free Radicals and Antioxidants, 3, S34-S41.
• [20] Pandey, D. K., Konjengbam, M., Dwivedi, P., Kaur, P., Kumar, V., Ray, D., Dey, A., (2021), Biotechnological interventions of in vitro propagation and production of valuable secondary metabolites in Stevia rebaudiana. Applied Microbiology and Biotechnology, 1-22.
• [21] Ahmad, M. A., Deng, X., Adeel, M., Rizwan, M., Shakoor, N., Yang, Y., Javed, R., (2022), Influence of calcium and magnesium elimination on plant biomass and secondary metabolites of Stevia rebaudiana Bertoni. Biotechnology and Applied Biochemistry, 69, 2008-2016.
• [22] Ulusu, F., Şahin, A., (2022), Changes in cytotoxic capacity, phenolic profile, total phenols and flavonoids of Nigella damascena L. seed extracts under different liquid fertilization. South African Journal of Botany, 150, 500-510.
• [23] Bouasla, I., Bouasla, A., Boumendjel, A., Messarah, M., Abdennour, C., Boulakoud, M. S., El Feki, A., (2014), Nigella sativa oil reduces aluminium chloride-induced oxidative injury in liver and erythrocytes of rats. Biological trace element research, 162, 252-261.
• [24] Naima, R., Oumam, M., Hannache, H., Sesbou, A., Charrier, B., Pizzi, A., Charrier–El Bouhtoury, F., (2015), Comparison of the impact of different extraction methods on polyphenols yields and tannins extracted from Moroccan Acacia mollissima barks. Industrial Crops and Products, 70, 245-252.
• [25] Zaidan, U. H., Hamid, S. N. M., Yusof, M. F. M., Ahmad, S., Abd Ghani, S. S., Shamsi, S., (2018), Chemical evaluation and antioxidant properties of extracts and essential oil from Stevia rebaudiana leaves. Malaysian Applied Biology, 47, 15-23.
• [26] Mahugo Santana, C., Sosa Ferrera, Z., Esther Torres Padrón, M., Juan Santana Rodríguez, J. (2009), Methodologies for the extraction of phenolic compounds from environmental samples: new approaches. Molecules, 14, 298-320.
• [27] Mohsen, S. M., Ammar, A. S., (2009), Total phenolic contents and antioxidant activity of corn tassel extracts. Food chemistry, 112, 595-598.
• [28] Zhang, Y., Cai, P., Cheng, G., Zhang, Y., (2022), A brief review of phenolic compounds identified from plants: Their extraction, analysis, and biological activity. Natural Product Communications, 17, 1934578X211069721.
• [29] Zeng, J., Cai, W., Yang, W., Wu, W., (2013), Antioxidant abilities, phenolics and flavonoids contents in the ethanolic extracts of the stems and leaves of different Stevia rebaudiana Bert lines. Sugar Tech, 15, 209-213.
• [30] Koroglu, A., Hurkul, M. M., Kendir, G., Kucukboyaci, N., (2019), In vitro antioxidant capacities and phenolic contents of four Erica L. (Ericaceae) taxa native to Turkey.
• [31] Turgay, O., Esen, Y., (2015), Antioxidant, total phenolic and antimicrobial characteristics of some species. Bulgarian Journal of Agricultural Science, 21, 498-503.
• [32] Aydın, F., Kahraman, Z. A., Türkoğlu, E. A., Müslüm, K. U. Z. U., Severoğlu, Z., (2021), In vitro antioxidant activity and carbonic anhydrase inhibitory features of Ferula communis extracts. International Journal of Agriculture Environment and Food Sciences, 5, 592-598.
• [33] Shukla, S., Mehta, A., Mehta, P., Bajpai, V. K., (2012), Antioxidant ability and total phenolic content of aqueous leaf extract of Stevia rebaudiana Bert. Experimental and Toxicologic Pathology, 64, 807-811.
• [34] Shukla, S., Mehta, A., Bajpai, V. K., Shukla, S., (2009), In vitro antioxidant activity and total phenolic content of ethanolic leaf extract of Stevia rebaudiana Bert. Food and Chemical Toxicology, 47, 2338-2343.
• [35] Tadhani, M. B., Patel, V. H., Subhash, R., (2007), In vitro antioxidant activities of Stevia rebaudiana leaves and callus. Journal of food composition and Analysis, 20, 323-329.
• [36] Nunes, R., Rodrigues, S., Pasko, P., Tyszka-Czochara, M., Grenha, A., de Carvalho, I. S., (2014), Effect of Erica australis extract on Caco-2 cells, fibroblasts and selected pathogenic bacteria responsible for wound infection. Industrial Crops and Products, 52, 99-104.
• [37] Guendouze-Bouchefa, N., Madani, K., Chibane, M., Boulekbache-Makhlouf, L., Hauchard, D., Kiendrebeogo, M., Duez, P. (2015). Phenolic compounds, antioxidant and antibacterial activities of three Ericaceae from Algeria. Industrial crops and products, 70, 459-466.
• [38] Santos, A., Luís, Â., Ferreira, S., Duarte, A. P., (2019), Antioxidant and antimicrobial activity and potential of heather (Erica spp.) extracts in the control of Listeria monocytogenes. International Journal of Food Science & Technology, 54, 862-870.
• [39] Sadki, C., Hacht, B., Souliman, A., Atmani, F., (2010), Acute diuretic activity of aqueous Erica multiflora flowers and Cynodon dactylon rhizomes extracts in rats. Journal of Ethnopharmacology, 128, 352-356.
• [40] Amroun, D., Hamoudi, M., Khennouf, S., Boutefnouchet, S., Harzallah, D., Amrane, M., Dahamna, S., (2021), In-vivo anti-inflammatory activity and safety assessment of the aqueous extract of Algerian Erica arborea L. (Ericaceae) aerial parts. Journal of Ethnopharmacology, 271, 113881.
• [41] Ghadimi, F., Mirzaie, A., Arasteh, J., (2019), Antibacterial and cytotoxicity of synthesized silver nanoparticles using Erica carnea extract on breast cancer cell line (MCF-7) and analysis of its apoptotic effects. Razi Journal of Medical Sciences, 26, 84-94.
• [42] Villareal, M. O., Han, J., Matsuyama, K., Sekii, Y., Smaoui, A., Shigemori, H., Isoda, H., (2013), Lupenone from Erica multiflora leaf extract stimulates melanogenesis in B16 murine melanoma cells through the inhibition of ERK1/2 activation. Planta medica, 79, 236-243.
• [43] Akaberi, M., Iranshahy, M., Iranshahi, M., (2015), Review of the traditional uses, phytochemistry, pharmacology and toxicology of giant fennel (Ferula communis L. subsp. communis). Iranian Journal of Basic Medical Sciences, 18, 1050.
• [44] Yoshino, Y., Tanaka, N., Tsuji, D., Itoh, K., Kashiwada, Y., (2023), Communiferulins, farnesylated coumarins from the roots of Ferula communis and their anti-neuroinflammatory activity. Journal of Natural Medicines, 77, 173-179.
• [45] Shivanna, N., Naika, M., Khanum, F., Kaul, V. K., (2013), Antioxidant, anti-diabetic and renal protective properties of Stevia rebaudiana. Journal of Diabetes and its Complications, 27, 103-113.
• [46] Ferrazzano, G. F., Cantile, T., Alcidi, B., Coda, M., Ingenito, A., Zarrelli, A., Pollio, A., (2015), Is Stevia rebaudiana Bertoni a non cariogenic sweetener? A review. Molecules, 21, 38.
• [47] Iatridis, N., Kougioumtzi, A., Vlataki, K., Papadaki, S., Magklara, A., (2022), Anti-cancer properties of Stevia rebaudiana; more than a sweetener. Molecules, 27, 1362.
• [48] Mehmood, A., Zhao, L., Ishaq, M., Xin, W., Zhao, L., Wang, C., Xu, M., (2020), Anti-hyperuricemic potential of stevia (Stevia rebaudiana Bertoni) residue extract in hyperuricemic mice. Food & Function, 11, 6387-6406.
• [49] Znati, M., Ben Jannet, H., Cazaux, S., Souchard, J. P., Harzallah Skhiri, F., Bouajila, J., (2014), Antioxidant, 5-lipoxygenase inhibitory and cytotoxic activities of compounds isolated from the Ferula lutea flowers. Molecules, 19, 16959-16975.
• [50] Deveci, E., Tel-Çayan, G., Duru, M. E., (2018), Phenolic profile, antioxidant, anticholinesterase, and anti-tyrosinase activities of the various extracts of Ferula elaeochytris and Sideritis stricta. International journal of food properties, 21, 771-783.
• [51] Chen, J. M., Ding, L., Sui, X. C., Xia, Y. M., Lu, T., (2016), Production of a bioactive sweetener steviolbioside via specific hydrolyzing ester linkage of stevioside with a β-galactosidase. Food chemistry, 196, 155-160.
• [52] Khare, N., Chandra, S., (2019), Stevioside mediated chemosensitization studies and cytotoxicity assay on breast cancer cell lines MDA-MB-231 and SKBR3. Saudi Journal of Biological Sciences, 26, 1596-1601.
• [53] Ibrahem, E. S., Ragheb, E. M., Yousef, F. M., Abdel-Azizand, M. F., Alghamdi, B. A., (2020), Nutritional value, cytotoxic and antimicrobial activities of Stevia rebaudiana leaf extracts. J. Biochem. Technol, 11, 108-115.