Myrtus communis L. subsp. communis Seeds Exhibit Potent Antioxidant Capacity, Enzyme Inhibition, and Selective Cytotoxicity Against Lung, Breast, Prostate, and Liver Human Cancer Cells

Year 2025, Volume: 55 Issue: 3, 435 - 443, 14.01.2026

Zühal Bayrakçeken Güven , Osman Tugay

https://doi.org/10.26650/IstanbulJPharm.2025.1728301

https://izlik.org/JA92ZH99UC

Abstract

Background and Aims: Myrtle (Myrtus communis L.) has been used as a food and folk medicine since ancient times. The aim of this study was to determine the antioxidant capacity, inhibition of tyrosinase enzyme, and cytotoxicity of 12 extracts from the fruit, seed, leaves, and twigs of Myrtus communis L. subsp. communis.

Methods: The cytotoxic effects on human lung (A549), liver (Hep3B), prostate (PC-3) and breast (MCF7) cancer cells and healthy L929 cells were determined using the MTT method. Tyrosinase enzyme inhibition was investigated using L-tyrosine as the substrate. The antioxidant capacity was determined using the DPPH, TEAC and CUPRAC methods.

Results: It was found that the extracts did not affect the viability of healthy cells but showed concentration- dependent toxic effects on cancer cells. The ethyl acetate sub-extracts of the plant parts showed a higher cytotoxic effect on all cell lines, and the ethyl acetate sub-extract of the seed was the most effective with 72.6% proliferation inhibition against the Hep3B. The methanol extract and ethyl acetate sub-extract of the seed showed the highest inhibition against tyrosinase and the values were 388.6 and 412.8 mg KAE/g extract, respectively. While all extracts showed significant antioxidant activities in all methods, the ethyl acetate sub-extract of seeds showed the highest.

Conclusion: This is the first comparative study to investigate the antiproliferative effects of extracts from various parts of Myrtus communis L. subsp. communis. The results show that seeds in particular can be a promising, effective and recyclable resource that can be safely used in the pharmaceutical and cosmetic industries.

Keywords

Antioxidant , Cytotoxicity , MTT , Myrtus communis L. , Tyrosinase

References

• Al-Najjar, B. O., Elshibani, F., Sharkasi, M. A., Shintiri, N. E., Naili, E. E., Abdulsayid, M., Abozayed, R. S., & Mohammed, H. A. (2025). Phytochemical analysis, bioactivity, and molecular docking studies of Myrtus communis L. seeds and fruit peel extracts demonstrating antioxidant and anti-tyrosinase properties. Scientific Reports, 15(1), 5634. google scholar
• Al-Snafi, A. E., Teibo, J. O., Shaheen, H. M., Akinfe, O. A., Teibo, T. K. A., Emieseimokumo, N., Elfiky, M. M., Al-Kuraishy, H. M., Al-Garbeeb, A. I., & Alexiou, A. (2024). The therapeutic value of Myrtus communis L.: an updated review. Naunyn^ Schmiedeberg's Archives of Pharmacology, 397(7), 4579-4600. google scholar
• Alipour, G., Dashti, S., & Hosseinzadeh, H. (2014). Review of pharmacological effects of Myrtus communis L. and its active constituents. Phytotherapy research, 28(8), 1125-1136. google scholar
• Apak, R., Güçlü, K., Demirata, B., Özyürek, M., Çelik, S. E., Bektaşoğlu, B., Berker, K. I., & Özyurt, D. (2007). Comparative evaluation of various total antioxidant capacity assays applied to phenolic compounds with the CUPRAC assay. Molecules, 12(7), 1496-1547. google scholar
• Azimi, M., & Hasheminasab, F. S. (2020). Evaluating the efficacy and safety of the myrtle (Myrtus communis) in treatment and prognosis of patients suspected to novel coronavirus disease (COVID-19): study protocol for a randomized controlled trial. Trials, 21, 1-5. google scholar
• Belahcene, S., Kebsa, W., Akingbade, T. V., Umar, H. I., Omoboyowa, D. A., Alshihri, A. A., Abo Mansour, A., Alhasaniah, A. H., Oraig, M. A., & Bakkour, Y. (2024). Chemical composition antioxidant and anti-inflammatory activities of Myrtus google scholar communis L. leaf extract: Forecasting ADMET profiling and anti-inflammatory targets using molecular docking tools. Molecules, 29(4), 849. google scholar
• Belahcene, S., Kebsa, W., Omoboyowa, D. A., Alshihri, A. A., Alelyani, M., Bakkour, Y., & Leghouchi, E. (2023). Unveiling the chemical profiling antioxidant and antiinflammatory activities of algerian Myrtus communis L. essential oils, and exploring molecular docking to predict the inhibitory compounds against cyclooxygenase-2. Pharmaceuticals, 16(10), 1343. google scholar
• Bilgic, N., & Duran, G. G. (2020). Chemical composition of Myrtus communis L. and Proapoptotic effects on the A549 cell line. Journal of Essential Oil Bearing Plants, 23(6), 1283-1295. google scholar
• Caputo, L., Capozzolo, F., Amato, G., De Feo, V., Fratianni, F., Vivenzio, G., & Nazzaro, F. (2022). Chemical composition, antibiofilm, cytotoxic, and antiacetylcholinesterase activities of Myrtus communis L. leaves essential oil. BMC complementary medicine and therapies, 22(1), 142. google scholar
• Chaudhary, P., Janmeda, P., Docea, A. O., Yeskaliyeva, B., Abdull Razis, A. F., Modu, B., Calina, D., & Sharifi-Rad, J. (2023). Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Frontiers in chemistry, 11, 1158198. google scholar
• Cheng, M.-J., Yang, X.-Y., Cao, J.-Q., Liu, C., Zhong, L.-P., Wang, Y., You, X.-F., Li, C.-C., Wang, L., & Ye, W.-C. (2019). Isolation, structure elucidation, and total synthesis of myrtuspirone A from Myrtus communis. Organic Letters, 21(6), 1583-1587. google scholar
• Chiocchio, I., Mandrone, M., Sanna, C., Maxia, A., Tacchini, M., & Poli, F. (2018). Screening of a hundred plant extracts as tyrosinase and elastase inhibitors, two enzymatic targets of cosmetic interest. Industrial crops and products, 122, 498-505. google scholar
• Cottiglia, F., Casu, L., Leonti, M., Caboni, P., Floris, C., Busonera, B., Farci, P., Ouhtit, A., & Sanna, G. (2012). Cytotoxic phloroglucinols from the leaves of Myrtus communis. Journal of Natural Products, 75(2), 225-229. google scholar
• Dabbaghi, M. M., Fadaei, M. S., Soleimani Roudi, H., Baradaran Rahimi, V., & Askari, V. R. (2023). A review of the biological effects of Myrtus communis. Physiological reports, 11(14), e15770. google scholar
• Franco, A. M., Tocci, N., Guella, G., Dell’Agli, M., Sangiovanni, E., Perenzoni, D., Vrhovsek, U., Mattivi, F., & Manca, G. (2019). Myrtle seeds (Myrtus communis L.) as a rich source of the bioactive ellagitannins oenothein B and eugeniflorin D2. ACS omega, 4(14), 15966-15974. google scholar
• Freshney, R. I. (2015). Culture of animal cells: a manual of basic technique and specialized applications. John Wiley & Sons. google scholar
• Güven, Z. B., Dogan, Z., Saracoglu, I., Picot, L., Nagatsu, A., & Basaran, A. A. (2022). Food plant with antioxidant, tyrosinase inhibitory and antimelanoma activity: Prunus mahaleb L. Food Bioscience, 48, 101804. google scholar
• Guzelmeric, E., Ugurlu, P., Celik, C., Sen, N. B., Helvacıoglu, S., Charehsaz, M., Erdogan, M., Ockun, M. A., Kırmızıbekmez, H., & Aydın, A. (2022). Myrtus communis L. (Myrtle) plant parts: Comparative assessment of their chemical compositions and antioxidant, anticancer, and antimutagenic activities. South African jour^ nal of botany, 150, 711-720. google scholar
• Harput, U. S., Genc, Y., & Saracoglu, I. (2012). Cytotoxic and antioxidative activities of Plantago lagopus L. and characterization of its bioactive compounds [10.1016/ j.fct.2012.01.019]. Food Chem. Toxicol., 50(5), 1554-1559. https://doi.org/10.1016/ j.fct.2012.01.019 google scholar
• Ibrahim, F. M., Fouad, R., El-Hallouty, S., Hendawy, S. F., Omer, E. A., & Mohammed, R. S. (2021). Egyptian Myrtus communis L. Essential oil Potential role as invitro Antioxidant, Cytotoxic and α-amylase Inhibitor. Egyptian Journal of Chemistry, 64(6), 3005-3017. google scholar
• Jelic, M. D., Mandic, A. D., Maricic, S. M., & Srdjenovic, B. U. (2021). Oxidative stress and its role in cancer. Journal of cancer research and therapeutics, 17(1), 22-28. google scholar
• Kim, J. H., Yoon, J.-Y., Yang, S. Y., Choi, S.-K., Kwon, S. J., Cho, I. S., Jeong, M. H., Ho Kim, Y., & Choi, G. S. (2017). Tyrosinase inhibitory components from Aloe vera and their antiviral activity [10.1080/14756366.2016.1235568]. J. Enzyme Inhib. Med. Chem., 32(1), 78-83. https://doi.org/10.1080/14756366.2016.1235568 google scholar
• Martín, T., Rubio, B., Villaescusa, L., Fernández, L., & Díaz, A. M. (1999). Polyphenolic compounds from pericarps of Myrtus communis. Pharmaceutical Biology, 37(1), 28-31. google scholar
• Mechchate, H., de Castro Alves, C. E., Es-Safi, I., Amaghnouje, A., Jawhari, F. Z., Costa de Oliveira, R., de Freitas Gomes, A., Conte, R., Soares Pontes, G., & Bousta, D. (2022). Antileukemic, Antioxidant, Anti-Inflammatory and Healing Activities google scholar Induced by a Polyphenol-Enriched Fraction Extracted from Leaves of Myrtus communis L. Nutrients, 14(23), 5055. google scholar
• Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65(1-2), 55-63. google scholar
• Moura, D., Vilela, J., Saraiva, S., Monteiro-Silva, F., De Almeida, J. M., & Saraiva, C. (2023). Antimicrobial effects and antioxidant activity of Myrtus communis L. essential oil in beef stored under different packaging conditions. Foods, 12(18), 3390. google scholar
• Moussa, A., Emam, A., Mohamed, M., & Diab, Y. (2010). In vitro evaluation of some Egyptian plants against the rot bacteria and spider mite and isolation the active constituent (s) from Myrtus communis leaves. International Food Re^ search Journal, 17, 287-294. google scholar
• Naraki, K., Rahbardar, M. G., Ajiboye, B. O., & Hosseinzadeh, H. (2023). The effect of ellagic acid on the metabolic syndrome: A review article. Heliyon, 9(11). google scholar
• Nassar, M. I., Aboutabl, E.-S. A., Ahmed, R. F., El-Khrisy, E.-D. A., Ibrahim, K. M., & Sleem, A. A. (2010). Secondary metabolites and bioactivities of Myrtus communis. Pharmacognosy research, 2(6), 325. google scholar
• Paknejad, M. S., Eftekhari, K., Rahimi, R., Vigeh, M., Naghizadeh, A., & Karimi, M. (2021). Myrtle (Myrtus communis L.) fruit syrup for gastroesophageal reflux disease in children: A double‐blind randomized clinical trial. Phytotherapy research, 35(11), 6369-6376. google scholar
• Pillaiyar, T., Manickam, M., & Namasivayam, V. (2017). Skin whitening agents: Medicinal chemistry perspective of tyrosinase inhibitors. Journal of enzyme inhibition and medicinal chemistry, 32(1), 403-425. google scholar
• Pillaiyar, T., Namasivayam, V., Manickam, M., & Jung, S.-H. (2018). Inhibitors of melanogenesis: an updated review. Journal of medicinal chemistry, 61(17), 7395-7418. google scholar
• Raeiszadeh, M., Esmaeili-Tarzi, M., Bahrampour-Juybari, K., Nematollahi-Mahani, S., Pardakhty, A., Nematollahi, M., & Mehrabani, M. (2018). Evaluation the effect of Myrtus communis L. extract on several underlying mechanisms involved in wound healing: An in vitro study. South African journal of botany, 118, 144-150. google scholar
• Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M., & Rice-Evans, C. (1999). Antioxidant activity applying an improved ABTS radical cation decolorization assay [10.1016/S0891-5849(98)00315-3]. Free Radical Biol. Med., 26(9/10), 1231-1237. https://doi.org/10.1016/S0891-5849(98)00315-3 google scholar
• Rossi, A., Di Paola, R., Mazzon, E., Genovese, T., Caminiti, R., Bramanti, P., Pergola, C., Koeberle, A., Werz, O., & Sautebin, L. (2009). Myrtucommulone from Myrtus communis exhibits potent anti-inflammatory effectiveness in vivo. The journal of pharmacology and experimental therapeutics, 329(1), 76-86. google scholar
• Şafak, E. K., İlgün, S., Çoban, K. N., Mutlu, S. A., Yılmaz, H., & Karatoprak, G. Ş. (2023). Antioxidant, Enzyme Inhibitory, and Cytotoxic Activity Screening of Myrtus communis L. Journal of Faculty of Pharmacy of Ankara University, 47(3), 827-835. google scholar
• Taibi, A., Mokrani, A., Kadi, A., Bouherour, R., Guermi, N. E. Y., Teffane, M., Arroul, Y., & Richard, T. (2025). Optimization of extraction conditions of phenolic compounds and antioxidant activity from myrtle (Myrtus communis L.) fruit. Chemistry & Biodiversity, 22(4), e202301675. google scholar
• Tretiakova, I., Blaesius, D., Maxia, L., Wesselborg, S., Schulze-Osthoff, K., Cinatl, J., Michaelis, M., & Werz, O. (2008). Myrtucommulone from Myrtus communis induces apoptosis in cancer cells via the mitochondrial pathway involving caspase-9. Apoptosis, 13(1), 119-131. google scholar
• Tumen, I., Senol, F. S., & Orhan, I. E. (2012). Inhibitory potential of the leaves and berries of Myrtus communis L.(myrtle) against enzymes linked to neurodegen-erative diseases and their antioxidant actions. International journal of food sciences and nutrition, 63(4), 387-392. google scholar
• Uysal, S., Sinan, K. I., & Zengin, G. (2023). Assessment of antioxidant and enzyme inhibition properties of Myrtus communis L. leaves. International Journal of Secondary Metabolite, 10(2), 166-174. google scholar
• Xing, X., Dan, Y., Xu, Z., & Xiang, L. (2022). Implications of oxidative stress in the pathogenesis and treatment of hyperpigmentation disorders. Oxidative medicine and cellular longevity, 2022(1), 7881717. google scholar
• Yoshimura, M., Amakura, Y., Tokuhara, M., & Yoshida, T. (2008). Polyphenolic compounds isolated from the leaves of Myrtus communis. Journal of natural medicines, 62, 366-368. google scholar