TY  - JOUR
T1  - The Preliminary Study on Phytochemical Profile and Antioxidant and Cytotoxic Activities of Harmal (Peganum harmala L.)
TT  - Üzerlik (Peganum harmala L.) Bitkisinin Fitokimyasal Profili, Antioksidan ve Sitotoksik Aktiviteleri Üzerine Ön Çalışma
AU  - Deveci, Ebru
AU  - Yılmaz Altınok, Bahar
AU  - Tel-çayan, Gülsen
PY  - 2025
DA  - June
Y2  - 2025
DO  - 10.31594/commagene.1607811
JF  - Commagene Journal of Biology
JO  - Comm. J. Biol.
PB  - ABADER (Adıyaman Bilimsel Araştırmalar Derneği)
WT  - DergiPark
SN  - 2602-456X
SP  - 71
EP  - 79
VL  - 9
IS  - 1
LA  - en
AB  - Harmal (Peganum harmala L.) is a perennial plant that has come to the fore with its medicinal use since ancient times. In this study, the phytochemical profile of the methanol extract of harmal was characterized by HPLC and total phenolic and flavonoid amounts were determined by spectrophotometric methods. Additionally, antioxidant and cytotoxic (HT-29 (human colon cancer line), HeLa (human cervical cancer line), and HEK-293 (human embryonic kidney 293)) activities were investigated. Among 20 different phytochemical compounds screened, the presence of catechin (2.65±0.01 mg/g), coumarin (0.96±0.01 mg/g), ascorbic acid (0.91±0.02 mg/g), protocatechuic acid (0.85±0.01 mg/g), gallic acid (0.60±0.01 mg/g), hesperidin (0.24±0.01 mg/g), ferulic acid (0.06±0.01 mg/g), rutin (0.04±0.01 mg/g), and trans-cinnamic acid (0.03±0.01 mg/g) were detected. Total phenolic amount was found as 63.80±0.13 µg GAE/mg extract and total flavonoid amount was found as 13.50±0.36 µg QE/mg extract. Harmal methanol extract showed varying degrees of antioxidant activity in ABTS•+ (IC50: 353.67±1.10 µg/mL), DPPH• (17.54±0.45%), CUPRAC (absorbance: 0.41±0.02), phosphomolybdenum (A0.50: 99.11±0.02 µg/mL), and metal chelating (38.47±0.77%) assays. Harmal methanol extract was low cytotoxic active on HT-29 cell line (> 800 µg/mL) and near-positive control cytotoxic active on HeLa cell line (IC50: 45.84±0.95 μg/mL). These findings highlight harmal as a valuable reserve in the search for natural antioxidant and cytotoxic (on HeLa cell line) agents, especially with respect to the research focusing on possible pharmaceutical and food additive applications.
KW  - Plant
KW  - HT-29 cell line
KW  - Methanol extract
KW  - HeLa cell line
KW  - HEK-293 cell line
KW  - HPLC
N2  - Üzerlik (Peganum harmala L.), antik çağlardan beri tıbbi kullanımı ile ön plana çıkan çok yıllık bir bitkidir. Bu çalışmada, üzerliğin metanol ekstresinin fitokimyasal profili HPLC ile karakterize edildi ve toplam fenolik ve flavonoid miktarları spektrofotometrik yöntemlerle belirlendi. Ayrıca, üzerliğin antioksidan ve sitotoksik (HT-29 (insan kolon kanseri hattı), HeLa (insan servikal kanser hattı) ve HEK-293 (insan embriyonik böbrek 293)) aktiviteleri araştırıldı. Taranan 20 farklı fitokimyasal bileşik arasında kateşin (2,65±0,01 mg/g), kumarin (0,96±0,01 mg/g), askorbik asit (0,91±0,02 mg/g), protokateşik asit (0,85±0,01 mg/g), gallik asit (0,60±0,01 mg/g), hesperidin (0,24±0,01 mg/g), ferulik asit (0,06±0,01 mg/g), rutin (0,04±0,01 mg/g) ve trans-sinnamik asit (0,03±0,01 mg/g) varlığı belirlendi. Toplam fenolik madde miktarı 63,80±0,13 µg GAE/mg ekstre ve toplam flavonoid miktarı 13,50±0,36 µg QE/mg ekstre olarak bulundu. Üzerlik metanol ekstresi, ABTS•+ (IC50: 353,67±1,10 µg/mL), DPPH• (%17,54±0,45), CUPRAC (absorbans: 0,41±0,02), fosfomolibden (A0,50: 99,11±0,02 µg/mL) ve metal kelatlama (%38,47±0,77) yöntemlerinde değişen derecelerde antioksidan aktivite gösterdi. Üzerlik metanol ekstresi HT-29 hücre hattında (> 800 µg/mL) düşük sitotoksik aktiviteye sahipken, HeLa hücre hattında (IC50: 45,84±0,95 μg/mL) pozitif kontrole yakın sitotoksik aktivite gösterdi. Bu bulgular, üzerliğin özellikle olası ilaç ve gıda katkı maddesi uygulamalarına odaklanan araştırmalar açısından doğal antioksidan ve sitotoksik (HeLa hücre hattına karşı) ajanların arayışında değerli bir rezerv olduğunu ortaya koymaktadır.
CR  - Abbas, M.W., Hussain, M., Qamar, M., Ali, S., Shafiq, Z., Wilairatana, P., & Mubarak, M.S. (2021). Antioxidant and anti-inflammatory effects of Peganum harmala extracts: An in vitro and in vivo study. Molecules, 26, 6084. https://doi.org/10.3390/molecules26196084
CR  - Abdullah, H., Mamat, N., Zakaria, N.M., Yunan, N.I.F.M., Hisham, M.I.N., & Hapidin, H. (2021). Combination effect of tamoxifen and ascorbic acid treatment on breast cancer cells (MCF-7) and cervical cancer cells (HeLa). Jurnal Sains Kesihatan Malaysia, 19(2), 1-6. https://doi.org/114. 10.17576/jskm-2021-1902-12
CR  - Ali, A., Riaz, S., Khalid, W., Fatima, M., Mubeen, U., Babar, Q., …, & Madilo, F.K. (2024). Potential of ascorbic acid in human health against different diseases: An updated narrative review. International Journal of Food Properties, 27, 493-515. https://doi.org/10.1080/10942912.2024.2327335
CR  - Altemimi, A., Lakhssassi, N., Baharlouei, A., Watson, D.G., & Lightfoot, D.A. (2017). Phytochemicals: Extraction, isolation, and identification of bioactive compounds from plant extracts. Plants, 6(4), 42. https://doi.org/10.3390/plants6040042
CR  - Alves, R.R., & Rosa, I.M. (2007). Biodiversity, traditional medicine and public health: Where do they meet?. Journal of Ethnobiology and Ethnomedicine, 3, 14. https://doi.org/10.1186/1746-4269-3-14
CR  - An, X., Yu, W., Liu, J., Tang, D., Yang, L., & Chen, X. (2024). Oxidative cell death in cancer: mechanisms and therapeutic opportunities. Cell Death & Disease, 15, 556. https://doi.org/10.1038/s41419-024-06939-5
CR  - Asgarpanah, J., & Ramezanloo, F. (2012). Chemistry, pharmacology and medicinal properties of Peganum harmala L. African Journal of Pharmacy and Pharmacology, 6(22), 1573-1580. https://doi.org/10.5897/AJPP11.876
CR  - Asma, S.T., Acaroz, U., Imre, K., Morar, A., Shah, S.R.A, Hussain, S.Z., … & Ince, S. (2022). Natural products/bioactive compounds as a source of anticancer drugs. Cancers (Basel), 14(24), 6203. https://doi.org/10.3390/cancers14246203
CR  - Ayoob, I., Hazari, Y.M., Lone, S.H., Rehman, S., Khuroo, M.A., Fazili, K.M., …, & Bhat, K.A. (2017). Phytochemical and cytotoxic evaluation of Peganum harmala: Structure activity relationship studies of harmine. Chemistry Select, 2, 2965-2968. https://doi.org/10.1002/slct.201700232
CR  - Balkrishna, A., Sharma, N., Srivastava, D., Kukreti, A., Srivastava, S., & Arya, V. (2024). Exploring the safety, efficacy, and bioactivity of herbal medicines: bridging traditional wisdom and modern science in healthcare. Future Integrative Medicine, 3(1), 35-49. https://doi.org/10.14218/FIM.2023.00086
CR  - Chuang, J.Y., Huang, Y.F., Lu, H.F., Ho, H.C., Yang, J.S., Li, T.M., …, & Chung, J.G. (2007). Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-κB down-regulation. In Vivo, 21(6), 1003-1009.
CR  - Chunarkar-Patil, P., Kaleem, M., Mishra, R., Ray, S., Ahmad, A., Verma, D., …, & Kumar, S. (2024). Anticancer drug discovery based on natural products: from computational approaches to clinical studies. Biomedicines, 12(1), 201. https://doi.org/10.3390/biomedicines12010201
CR  - Davis, C.C., & Choisy, P. (2024). Medicinal plants meet modern biodiversity science. Current Biology, 34, R158-R173. https://doi.org/10.1016/j.cub.2023.12.038
CR  - Deveci, E., Tel-Çayan, G., Çayan, F., Yılmaz Altınok, B., & Aktaş, S. (2024). Characterization of polysaccharide extracts of four edible mushrooms and determination of in vitro antioxidant, enzyme inhibition and anticancer activities. ACS Omega, 9, 25887-25901. https://doi.org/10.1021/acsomega.4c00322
CR  - Deveci, E., Yılmaz Altınok, B., & Tel-Çayan, G. (2023). A study on phytochemical composition, antioxidant, and anti-cancer activities of Gingko biloba L. Commagene Journal of Biology, 7(2), 99-106. https://doi.org/10.31594/commagene.1322069
CR  - Edziri, H., Mastouri, M., Mahjoub, M.A., Patrich, G., Matieu, M., Ammar, S., …, & Aouni, M. (2010). Antibacterial, antiviral and antioxidant activities of aerial part extracts of Peganum harmala L. grown in Tunisia. Toxicological & Environmental Chemistry, 92(7), 1283-1292. https://doi.org/10.1080/02772240903450736
CR  - Elansary, H.O., Szopa, A., Kubica, P., Ekiert, H., Al-Mana, F.A., & El-Shafei, A.A. (2020a). Polyphenols of Frangula alnus and Peganum harmala leaves and associated biological activities. Plants (Basel), 9(9), 1086. https://doi.org/10.3390/plants9091086.
CR  - Elansary, H.O., Szopa, A., Kubica, P., El-Ansary, D.O., Ekiert, H., & Al-Mana, F.A. (2020b). Malus baccata var. gracilis and Malus toringoides Bark polyphenol studies and antioxidant, antimicrobial and anticancer activities. Processes, 8, 283. https://doi.org/10.3390/pr8030283
CR  - Elmusa, F., & Elmusa, M. (2024). Mini-review on coumarins: Sources, biosynthesis, bioactivity, extraction and toxicology. Journal of the Turkish Chemical Society Section A: Chemistry, 11, 933-944. https://doi.org/10.18596/jotcsa.1419322
CR  - Grigalius, I., & Petrikaite, V. Relationship between antioxidant and anticancer activity of trihydroxyflavones. Molecules, 22(12), 2169. https://doi.org/10.3390/molecules22122169
CR  - Gu, X., Mu, C., Zheng, R., Zhang, Z., Zhang, Q., & Liang, T. (2024). The cancer antioxidant regulation system in therapeutic resistance. Antioxidants, 13, 778. https://doi.org/10.3390/antiox13070778
CR  - Gür, M., Güder, A., Verep, D., Güney, K., Özkan, O.E., Seki, N., & Kandemirli, F. (2018). Some important plants for epilepsy treatment: Antioxidant activity and flavonoid compositions. Iranian Journal of Science and Technology, Transactions A: Science, 42, 1847-1857. https://doi.org/10.1007/s40995-017-0361-3
CR  - Hasan, R., Haque, M.M., Hoque, A., Sultana, S., Rahman, M.M., Shaikh, A.A., & Sarker, K.U. (2024). Antioxidant activity study and GC-MS profiling of Camellia sinensis Linn. Heliyon, 10, e23514 https://doi.org/10.1016/j.heliyon.2023.e23514
CR  - Hayes, J.D., Dinkova-Kostova, A.T., & Tew, K.D. (2020). Oxidative stress in cancer. Cancer Cell, 38, 167-197. https://doi.org/10.1016/j.ccell.2020.06.001
CR  - Jaradat, N., Hawash, M., Sharifi‑Rad, M., Shakhshir, A., Sobuh, S., Hussein, F., …, & Ibrahim, A.N. (2024). Insights into free radicals scavenging, α‑amylase inhibition, cytotoxic and antifibrotic activities unveiled by Peganum harmala extracts. BMC Complementary Medicine and Therapies, 24, 299. https://doi.org/10.1186/s12906-024-04602-2
CR  - Kamran, M.Z., Din, M., Sahu, M.R., Ahmad, J., Bilal, Bilal, M., Jamil, N., Yasir, M., & Kanwal, Q. (2024). Bioactivities of Cholistani harmal (Peganum harmala) with exploration of bioactive phytochemicals. International Journal of Chemical and Biochemical Sciences, 25(19), 105-116. https://doi.org/10.62877/12-IJCBS-24-25-19-12
CR  - Kemel, H., Benguedouar, L., Boudjerda, D., Menadi, S., Cacan, E., & Sifour, E. (2024). Phytochemical profiling, cytotoxic, anti‑migration, and anti‑angiogenic potential of phenolic‑rich fraction from Peganum harmala: in vitro and in ovo studies. Medical Oncology, 41, 144. https://doi.org/10.1007/s12032-024-02396-4
CR  - Khalid, M., Al-Rimawi, F., Darwish, S., Salah, Z., Alnasser, S.M., Wedian, F., …, & Al-Mazaideh, G.M. (2024). Assessment of the anticancer, antimicrobial, and antioxidant activities of the Peganum harmala L. plant. Natural Product Communications, 2024, 19(6), 1-10. https://doi.org/10.1177/1934578X241260597
CR  - Ladas, E.J., Jacobson, J.S., Kennedy, D.D., Teel, K., Fleischauer, A., & Kelly, K.M. (2004). Antioxidants and cancer therapy: A systematic review. Journal of Clinical Oncology, 22(3), 517-528. https://doi.org/10.1200/JCO.2004.03.086
CR  - Liu, B., Zhou, H., Tan, L., Siu, K.T.H., & Guan, X.Y. (2024). Exploring treatment options in cancer: Tumor treatment strategies. Signal Transduction and Targeted Therapy, 9, 175. https://doi.org/10.1038/s41392-024-01856-7
CR  - Liu, W., Zhang, Z., Zhang, T., Qiao, Q., & Hou, X. (2022). Phenolic profiles and antioxidant activity in different organs of Sinopodophyllum hexandrum. Frontiers in Plant Science, 13, 1037582. https://doi.org/10.3389/fpls.2022.1037582
CR  - Luo, M., Zhou, L., Huang, Z., Li, B., Nice, E.C., Xu, J., & Huang, C. (2022). Antioxidant therapy in cancer: Rationale and progress. Antioxidants, 11, 1128. https://doi.org/10.3390/antiox11061128
CR  - Mazandarani, M., Sepehr, K.S., Baradaran, B., & Khuri, V. (2012). Autecology, phytochemical and antioxidant activity of Peganum harmala L. seed extract in North of Iran (Tash Mountains). Journal of Medicinal Plants and By-products, 2, 151-156. https://doi.org/10.22092/jmpb.2012.108479
CR  - Moloudizargari, M., Mikaili, P., Aghajanshakeri, S., Asghari, M.H., & Shayegh, J. (2013). Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids. Pharmacognosy Reviews, 7, 199-212. https://doi.org/10.4103/0973-7847.120524
CR  - Mounira, D., Abdelouahab, D., Widad, F., Riadh, B.M., Farid, B., & Ahmed, B. (2022). Cytotoxic, antioxidant and antimicrobial activities of Peganum harmala L. extracts. Biotechnologia Acta, 15, 61-71. https://doi.org/10.15407/biotech15.01.061
CR  - Nait Marzoug, A., Khaldi, F., Ayari, A., Gali, L., & Gheid, A. (2023). Antioxidant and anticholinesterase effects of methanol extract, and consecutive fractions of Peganum harmala L. Egyptian Journal of Chemistry, 66(6), 431-440. https://doi.org/10.21608/ejchem.2022.151986.6663
CR  - Nazir, F., Nawaz-ur-Rehman, S., Khadim, S., Amber, S., Ameen, F., Ahmad, … & Iqbal, M. (2024). Analytical characterization, antioxidant, antiviral and antimicrobial potential of selected medicinal plants. Natural Product Communications, 19(9), 1-15.  https://doi.org/10.1177/1934578X241274986
CR  - Park, Y.K., Koo, M.H., Ikegaki, M., & Contado, J.L. (1997). Comparison of the flavonoid aglycone contents of Apis mellifera propolis from various regions of Brazil. Brazilian Archives of Biology and Technology, 40, 97-106.
CR  - Rahmaddiansyah, R., Hasani, S., Zikrah, A.A., & Arisanty, D. (2022). The effect of gambier catechin isolate on cervical cancer cell death (HeLa cell lines). Open Access Macedonian Journal of Medical Sciences, 10(B), 1293-1297. https://doi.org/10.3889/oamjms.2022.8779
CR  - Sheng, Y., Sun, Y., Tang, Y., Yu, Y., Wang, J., Zheng, F., …, & Sun, Y. (2023). Catechins: Protective mechanism of antioxidant stress in atherosclerosis. Frontiers in Pharmacology, 14, 1144878. https://doi.org/10.3389/fphar.2023.1144878
CR  - Slinkard, K., & Singleton, V.L. (1977) Total phenol analyses: Automation and comparison with manual methods. American Journal of Enology and Viticulture, 28, 49-55.
CR  - Tosun, M., Ercisli, S., Sengul, M., Ozer, H., & Polat, T. (2009). Antioxidant properties and total phenolic content of eight Salvia species from Turkey. Biological Research, 41, 175-181. https://doi.org/10.4067/S0716-97602009000200005
CR  - Wang, G., Liu, Y., Zhang, L., An, L., Chen, R., Liu, Y., …, & Xue, Y. (2020). Computational study on the antioxidant property of coumarin-fused coumarins. Food Chemistry, 304, 125446. https://doi.org/10.1016/j.foodchem.2019.125446
CR  - Yılmaz, B. (2022). Release of nifedipine, furosemide, and niclosamide drugs from the biocompatible poly (HEMA) hydrogel structures. Turkish Journal of Chemistry, 46(5), 1710-1722. https://doi.org/10.55730/1300-0527.3474
CR  - Zhang, S., Gai, Z., Gui, T., Chen, J., Chen, Q., & Li, Y.  (2021). Antioxidant effects of protocatechuic acid and protocatechuic aldehyde: Old wine in a new bottle. Evidence-Based Complementary and Alternative Medicine, 8, 6139308. https://doi.org/10.1155/2021/6139308
UR  - https://doi.org/10.31594/commagene.1607811
L1  - https://dergipark.org.tr/tr/download/article-file/4469321
ER  -