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Antioxidant and Anti-Growth Properties of Selected Anatolian Plant Species: Exploring the Potential of Heracleum humile, Doronicum reticulatum, Centaurea drabifolia, and Senecio olympicus

Yıl 2023, Cilt: 2 Sayı: Kongre Özel Sayısı - 3. Uluslararası Multidisipliner Kanser Araştırmaları Kongresi, 102 - 111, 31.10.2023
https://doi.org/10.59312/ebshealth.1366959

Öz

This study investigated the anti-growth and antioxidant properties of four plant species native to the Anatolian region: Heracleum humile, Doronicum reticulatum, Centaurea drabifolia, and Senecio olympicus. Plant materials were collected, authenticated, and extracted using a Soxhlet apparatus. The growth inhibitory activities of the extracts were evaluated in human breast cancer cell lines MCF-7 and MDA-MB-231, and the nonmalignant immortalized human breast cell line MCF-10A, using the sulforhodamine B (SRB) assay. Antioxidant capacities were assessed via DPPH and CUPRAC assays. The results demonstrated that C. drabifolia extract exhibited potent cytotoxic effects, while D. reticulatum displayed selective toxicity and the most pronounced antioxidant activity among the evaluated species. These findings contribute to our understanding of the therapeutic potential of these indigenous plant species in addressing various public health issues, including cancer.

Destekleyen Kurum

Bursa Büyükşehir Belediyesi

Proje Numarası

N/A

Teşekkür

This work was funded by Bursa Municipality within the scope of bilateral cooperation with Bursa Uludag University. The authors would like to thank Prof. Engin Ulukaya (MD, PhD) for his valuable support and Prof. Gurcan Guleryuz (PhD) for his support in collection and identification of the plants.

Kaynakça

  • Acito, M., Russo, C., Fatigoni, C., Mercanti, F., Moretti, M., & Villarini, M. (2022). Cytotoxicity and Genotoxicity of Senecio vulgaris L. Extracts: An In Vitro Assessment in HepG2 Liver Cells. International Journal of Environmental Research and Public Health, 19(22), 14824. https://doi.org/10.3390/ijerph192214824
  • Albayrak, S., Aksoy, A., Yurtseven, L., & Yaşar, A. (2014). A comparative study on phenolic components and biological activity of some Senecio species in Turkey. Journal of Pharmacy and Pharmacology, 66(11), 1631-1640. https://doi.org/10.1111/jphp.12288
  • Amani, Z., Gandomi, H., Akhondzadeh Basti, A., Derakhshandeh, A., & Noori, N. (2019). Cytotoxicity, genotoxicity, and mutagenicity potential of ethanolic extract of Heracleum persicum Desf. ex Fischer. Journal of Food Safety, 39(3), e12640. https://doi.org/10.1111/jfs.12640
  • Apak, R., Güçlü, K., Özyürek, M., Karademir, S. E., & Altun, M. (2005). Total antioxidant capacity assay of human serum using copper (II)-neocuproine as chromogenic oxidant: the CUPRAC method. Free Radical Research, 39, 949-961. https://doi.org/10.1080/10715760500210145
  • Arnold, N., Baydoun, S., Chalak, L., & Raus, T. (2015). A contribution to the flora and ethnobotanical knowledge of Mount Hermon, Lebanon. Flora Mediterranea, 25, 13-55. https://doi.org/10.7320/FlMedit25.013
  • Badalamenti, N., Modica, A., Ilardi, V., & Bruno, M. (2021). Chemical constituents and biological properties of genus Doronicum (Asteraceae). Chemistry & Biodiversity, 18(12), e2100631. https://doi.org/10.1002/cbdv.202100631
  • Bahadori, M. B., Dinparast, L., & Zengin, G. (2016). The genus Heracleum: a comprehensive review on its phytochemistry, pharmacology, and ethnobotanical values as a useful herb. Comprehensive Reviews in Food Science and Food Safety, 15(6), 1018-1039. https://doi.org/10.1111/1541-4337.12222
  • Candan, F., Uysal, T., Tugay, O., Bozkurt, M., Ertuğrul, K., & Demirelma, H. (2016). The examinations of achene ultrastructural features of section Acrolophus (Centaurea, Asteraceae) via scanning electron microscopy. Turkish Journal of Botany, 40(2), 147-163. https://doi.org/10.3906/bot-1503-51
  • Doral, G., & Wink, M. (2002). Chemical composition and biological activity of the essential oils of Senecio aegyptius var. discoideus Boiss. Zeitschrift fuer Naturforschung C, 57(5-6), 434-439. https://doi.org/10.1515/znc-2002-5-605
  • Fabricant, D. S., & Farnsworth, N. R. (2001). The value of plants used in traditional medicine for drug discovery. Environmental Health Perspectives, 109, 69-75. https://doi.org/10.1289/ehp.01109s169
  • Formisano, C., Sirignano, C., Rigano, D., Chianese, G., Zengin, G., Seo, E. J., ... & Taglialatela-Scafati, O. (2017). Antiproliferative activity against leukemia cells of sesquiterpene lactones from the Turkish endemic plant Centaurea drabifolia subsp. detonsa. Fitoterapia, 120, 98-102. https://doi.org/10.1016/j.fitote.2017.05.016
  • Gupta, D., Bleakley, B., & Gupta, R. K. (2011). Phytochemical analysis and antioxidant activity of herbal plant Doronicum hookeri Hook F.(Asteraceae). Journal of Medicinal Plants Research, 5(13), 2736-2742.
  • Güven, S., Umdu Topsakal, Ü., & Beyazoğlu, O. (2020). Chromosome Counts of Some Doronicum (Asteraceae: Senecioneae) Taxa from Turkey. Journal of Anatolian Environmental and Animal Sciences, 5(4), 605-610. https://doi.org/10.35229/jaes.799202
  • Kargıoğlu, M., Cenkci, S., Serteser, A., Konuk, M., & Vural, G. (2010). Traditional uses of wild plants in the middle Aegean region of Turkey. Human Ecology, 38, 429-450. https://doi.org/10.1007/s10745-010-9318-2
  • Khammar, A., & Djeddi, S. (2012). Pharmacological and biological properties of some Centaurea species. European Journal of Scientific Research, 84(3), 398-416.
  • Kirmizi, S., Güleryüz, G., & Arslan, H. (2011). Germination responses to GA3 and short‐time chilling of three endemic species: Tripleurospermum pichleri, Cirsium leucopsis and Senecio olympicus (Asteraceae). Plant Species Biology, 26, 51-57. https://doi.org/10.1111/j.1442-1984.2010.00302.x
  • Logacheva, M. D., Valiejo-Roman, C. M., & Pimenov, M. G. (2008). ITS phylogeny of West Asian Heracleum species and related taxa of Umbelliferae-Tordylieae WDJ Koch, with notes on evolution of their psbA-trnH sequences. Plant Systematics and Evolution, 270, 139-157. https://doi.org/10.1007/s00606-007-0619-x
  • Loizzo, M. R., Tundis, R., Statti, G. A., & Menichini, F. (2007). Jacaranone: a cytotoxic constituent from Senecio ambiguus subsp. ambiguus (Biv.) DC. against renal adenocarcinoma ACHN and prostate carcinoma LNCaP cells. Archives of Pharmacal Research, 30, 701-707. https://doi.org/10.1007/BF02977631
  • Maggi, F., Quassinti, L., Bramucci, M., Lupidi, G., Petrelli, D., Vitali, L. A., ... & Vittori, S. (2014). Composition and biological activities of hogweed [Heracleum sphondylium L. subsp. ternatum (Velen.) Brummitt] essential oil and its main components octyl acetate and octyl butyrate. Natural Product Research, 28(17), 1354-1363. https://doi.org/10.1080/14786419.2014.904311
  • Manayi, A., Rastegari, A., Heydarian, B., Vahedi-Mazdabadi, Y., Khanavi, M., Akbarzadeh, T., & Saeedi, M. (2021). Phytochemical investigation and biological activity of Doronicum pardalianches L. roots against Alzheimer's disease. Natural Product Research, 1-5. https://doi.org/10.1080/14786419.2021.1999944
  • Marzocco, S., Adesso, S., Alilou, M., Stuppner, H., & Schwaiger, S. (2017). Anti-inflammatory and anti-oxidant potential of the root extract and constituents of Doronicum austriacum. Molecules, 22(6), 1003. https://doi.org/10.3390/molecules22061003
  • Molyneux, P. (2004). The use of the stable free radical diphenylpicrylhydrazyl (DPPH) for estimating antioxidant activity. Songklanakarin Journal of Science and Technology, 26, 211-219.
  • Ocal, M., Altunoglu, Y. C., Angeloni, S., Mustafa, A. M., Caprioli, G., Zengin, G., ... & Baloglu, M. C. (2022). Comparative Content, Biological and Anticancer Activities of Heracleum humile Extracts Obtained by Ultrasound‐Assisted Extraction Method. Chemistry & Biodiversity, 19(7), e202101040. https://doi.org/10.1002/cbdv.202101040
  • POWO. (2023). Plants of the World Online. Retrieved from http://www.plantsoftheworldonline.org/. Sarimahmut, M., & Celikler, S. (2023). Plants from Northwestern Anatolia Display Selective Cytotoxicity and Induce Mitotic Catastrophe: A Study on Anticancer and Genotoxic Activities. Chemistry & Biodiversity, e202300460. https://doi.org/10.1002/cbdv.202300460
  • Tundis, R., Loizzo, M. R., Bonesi, M., Menichini, F., Dodaro, D., Passalacqua, N. G., ... & Menichini, F. (2009). In vitro cytotoxic effects of Senecio stabianus Lacaita (Asteraceae) on human cancer cell lines. Natural Product Research, 23(18), 1707-1718. https://doi.org/10.1080/14786410802194151
  • Türe, C., & Böcük, H. (2010). Distribution patterns of threatened endemic plants in Turkey: A quantitative approach for conservation. Journal for Nature Conservation, 18, 296-303. https://doi.org/10.1016/j.jnc.2010.01.002
  • Uğur, A., Ertem, H., & Beyatlι, Y. (2006). Antibacterial Properties of Senecio sandrasicus on Multidrug-Resistant Stenotrophomonas maltophilia. Pharmaceutical Biology, 44(4), 253-257. https://doi.org/10.1080/13880200600713865
  • Ugur, A., Sarac, N., Duru, M. E., & Beyatli, Y. (2009). In vitro study of antibacterial activity on multi-resistant bacteria and chemical composition of the chloroform extract of endemic Centaurea drabifolia subsp. cappadocica. Natural Product Communications, 4(9), 1934578X0900400922. https://doi.org/10.1177/1934578X0900400922
  • Wang, W. S., Lu, P., Duan, C. H., & Feng, J. C. (2010). A new jacaranone derivative from Senecio scandens var. incisus. Natural Product Research, 24(4), 370-374. https://doi.org/10.1080/14786410903250936
  • Yirtici, Ü., Göger, F., Sarimahmut, M., & Ergene, A. (2017). Cytotoxic and apoptotic effects of endemic Centaurea fenzlii Reichardt on the MCF-7 breast cancer cell line. Turkish Journal of Biology, 41, 370-377. https://doi.org/10.3906/biy-1609-74
  • Zengin, G., Mahoomodally, M. F., Sinan, K. I., Bakar, K., Jugreet, S., Yildiztugay, E., ... & Caprioli, G. (2022). A Comparative Study of Chemical Profiling and Biological Effects of Doronicum orientale Extracts. Chemistry & Biodiversity, 19(4), e202200076. https://doi.org/10.1002/cbdv.202200076
  • Zengin, G., Zheleva-Dimitrova, D., Gevrenova, R., Nedialkov, P., Mocan, A., Ćirić, A., ... & Mahomoodally, M. F. (2018). Identification of phenolic components via LC-MS analysis and biological activities of two Centaurea species: C. drabifolia subsp. drabifolia and C. lycopifolia. Journal of Pharmaceutical and Biomedical Analysis, 149, 436-441. https://doi.org/10.1016/j.jpba.2017.11.045

Seçilen Anadolu Bitki Türlerinin Antioksidan ve Anti-Büyüme Özellikleri: Heracleum humile, Doronicum reticulatum, Centaurea drabifolia ve Senecio olympicus'un Potansiyelini Keşfetme

Yıl 2023, Cilt: 2 Sayı: Kongre Özel Sayısı - 3. Uluslararası Multidisipliner Kanser Araştırmaları Kongresi, 102 - 111, 31.10.2023
https://doi.org/10.59312/ebshealth.1366959

Öz

Bu çalışma, Anadolu bölgesine özgü dört bitki türünün anti-büyüme ve antioksidan özelliklerini incelemiştir: Heracleum humile, Doronicum reticulatum, Centaurea drabifolia ve Senecio olympicus. Bitki materyalleri toplanmış, doğrulanmış ve bir Soxhlet aygıtı kullanılarak ekstrakte edilmiştir. Ekstrelerin büyüme inhibe edici aktiviteleri, insan meme kanseri hücre hatları MCF-7 ve MDA-MB-231 ve malignan olmayan ölümsüzleştirilmiş insan meme hücre hattı MCF-10A üzerinde sülfarodamin B (SRB) testi kullanılarak değerlendirildi. Antioksidan kapasiteler DPPH ve CUPRAC testleri ile değerlendirildi. Sonuçlar, C. drabifolia ekstresinin güçlü sitotoksik etkilere sahip olduğunu gösterirken, D. reticulatum seçici toksisite sergiledi ve değerlendirilen türler arasında en belirgin antioksidan aktiviteye sahipti. Bu bulgular, söz konusu yerli bitki türlerinin, kanser de dâhil olmak üzere çeşitli halk sağlığı sorunlarına yönelik terapötik potansiyellerini anlamamıza katkı sağlamaktadır.

Proje Numarası

N/A

Kaynakça

  • Acito, M., Russo, C., Fatigoni, C., Mercanti, F., Moretti, M., & Villarini, M. (2022). Cytotoxicity and Genotoxicity of Senecio vulgaris L. Extracts: An In Vitro Assessment in HepG2 Liver Cells. International Journal of Environmental Research and Public Health, 19(22), 14824. https://doi.org/10.3390/ijerph192214824
  • Albayrak, S., Aksoy, A., Yurtseven, L., & Yaşar, A. (2014). A comparative study on phenolic components and biological activity of some Senecio species in Turkey. Journal of Pharmacy and Pharmacology, 66(11), 1631-1640. https://doi.org/10.1111/jphp.12288
  • Amani, Z., Gandomi, H., Akhondzadeh Basti, A., Derakhshandeh, A., & Noori, N. (2019). Cytotoxicity, genotoxicity, and mutagenicity potential of ethanolic extract of Heracleum persicum Desf. ex Fischer. Journal of Food Safety, 39(3), e12640. https://doi.org/10.1111/jfs.12640
  • Apak, R., Güçlü, K., Özyürek, M., Karademir, S. E., & Altun, M. (2005). Total antioxidant capacity assay of human serum using copper (II)-neocuproine as chromogenic oxidant: the CUPRAC method. Free Radical Research, 39, 949-961. https://doi.org/10.1080/10715760500210145
  • Arnold, N., Baydoun, S., Chalak, L., & Raus, T. (2015). A contribution to the flora and ethnobotanical knowledge of Mount Hermon, Lebanon. Flora Mediterranea, 25, 13-55. https://doi.org/10.7320/FlMedit25.013
  • Badalamenti, N., Modica, A., Ilardi, V., & Bruno, M. (2021). Chemical constituents and biological properties of genus Doronicum (Asteraceae). Chemistry & Biodiversity, 18(12), e2100631. https://doi.org/10.1002/cbdv.202100631
  • Bahadori, M. B., Dinparast, L., & Zengin, G. (2016). The genus Heracleum: a comprehensive review on its phytochemistry, pharmacology, and ethnobotanical values as a useful herb. Comprehensive Reviews in Food Science and Food Safety, 15(6), 1018-1039. https://doi.org/10.1111/1541-4337.12222
  • Candan, F., Uysal, T., Tugay, O., Bozkurt, M., Ertuğrul, K., & Demirelma, H. (2016). The examinations of achene ultrastructural features of section Acrolophus (Centaurea, Asteraceae) via scanning electron microscopy. Turkish Journal of Botany, 40(2), 147-163. https://doi.org/10.3906/bot-1503-51
  • Doral, G., & Wink, M. (2002). Chemical composition and biological activity of the essential oils of Senecio aegyptius var. discoideus Boiss. Zeitschrift fuer Naturforschung C, 57(5-6), 434-439. https://doi.org/10.1515/znc-2002-5-605
  • Fabricant, D. S., & Farnsworth, N. R. (2001). The value of plants used in traditional medicine for drug discovery. Environmental Health Perspectives, 109, 69-75. https://doi.org/10.1289/ehp.01109s169
  • Formisano, C., Sirignano, C., Rigano, D., Chianese, G., Zengin, G., Seo, E. J., ... & Taglialatela-Scafati, O. (2017). Antiproliferative activity against leukemia cells of sesquiterpene lactones from the Turkish endemic plant Centaurea drabifolia subsp. detonsa. Fitoterapia, 120, 98-102. https://doi.org/10.1016/j.fitote.2017.05.016
  • Gupta, D., Bleakley, B., & Gupta, R. K. (2011). Phytochemical analysis and antioxidant activity of herbal plant Doronicum hookeri Hook F.(Asteraceae). Journal of Medicinal Plants Research, 5(13), 2736-2742.
  • Güven, S., Umdu Topsakal, Ü., & Beyazoğlu, O. (2020). Chromosome Counts of Some Doronicum (Asteraceae: Senecioneae) Taxa from Turkey. Journal of Anatolian Environmental and Animal Sciences, 5(4), 605-610. https://doi.org/10.35229/jaes.799202
  • Kargıoğlu, M., Cenkci, S., Serteser, A., Konuk, M., & Vural, G. (2010). Traditional uses of wild plants in the middle Aegean region of Turkey. Human Ecology, 38, 429-450. https://doi.org/10.1007/s10745-010-9318-2
  • Khammar, A., & Djeddi, S. (2012). Pharmacological and biological properties of some Centaurea species. European Journal of Scientific Research, 84(3), 398-416.
  • Kirmizi, S., Güleryüz, G., & Arslan, H. (2011). Germination responses to GA3 and short‐time chilling of three endemic species: Tripleurospermum pichleri, Cirsium leucopsis and Senecio olympicus (Asteraceae). Plant Species Biology, 26, 51-57. https://doi.org/10.1111/j.1442-1984.2010.00302.x
  • Logacheva, M. D., Valiejo-Roman, C. M., & Pimenov, M. G. (2008). ITS phylogeny of West Asian Heracleum species and related taxa of Umbelliferae-Tordylieae WDJ Koch, with notes on evolution of their psbA-trnH sequences. Plant Systematics and Evolution, 270, 139-157. https://doi.org/10.1007/s00606-007-0619-x
  • Loizzo, M. R., Tundis, R., Statti, G. A., & Menichini, F. (2007). Jacaranone: a cytotoxic constituent from Senecio ambiguus subsp. ambiguus (Biv.) DC. against renal adenocarcinoma ACHN and prostate carcinoma LNCaP cells. Archives of Pharmacal Research, 30, 701-707. https://doi.org/10.1007/BF02977631
  • Maggi, F., Quassinti, L., Bramucci, M., Lupidi, G., Petrelli, D., Vitali, L. A., ... & Vittori, S. (2014). Composition and biological activities of hogweed [Heracleum sphondylium L. subsp. ternatum (Velen.) Brummitt] essential oil and its main components octyl acetate and octyl butyrate. Natural Product Research, 28(17), 1354-1363. https://doi.org/10.1080/14786419.2014.904311
  • Manayi, A., Rastegari, A., Heydarian, B., Vahedi-Mazdabadi, Y., Khanavi, M., Akbarzadeh, T., & Saeedi, M. (2021). Phytochemical investigation and biological activity of Doronicum pardalianches L. roots against Alzheimer's disease. Natural Product Research, 1-5. https://doi.org/10.1080/14786419.2021.1999944
  • Marzocco, S., Adesso, S., Alilou, M., Stuppner, H., & Schwaiger, S. (2017). Anti-inflammatory and anti-oxidant potential of the root extract and constituents of Doronicum austriacum. Molecules, 22(6), 1003. https://doi.org/10.3390/molecules22061003
  • Molyneux, P. (2004). The use of the stable free radical diphenylpicrylhydrazyl (DPPH) for estimating antioxidant activity. Songklanakarin Journal of Science and Technology, 26, 211-219.
  • Ocal, M., Altunoglu, Y. C., Angeloni, S., Mustafa, A. M., Caprioli, G., Zengin, G., ... & Baloglu, M. C. (2022). Comparative Content, Biological and Anticancer Activities of Heracleum humile Extracts Obtained by Ultrasound‐Assisted Extraction Method. Chemistry & Biodiversity, 19(7), e202101040. https://doi.org/10.1002/cbdv.202101040
  • POWO. (2023). Plants of the World Online. Retrieved from http://www.plantsoftheworldonline.org/. Sarimahmut, M., & Celikler, S. (2023). Plants from Northwestern Anatolia Display Selective Cytotoxicity and Induce Mitotic Catastrophe: A Study on Anticancer and Genotoxic Activities. Chemistry & Biodiversity, e202300460. https://doi.org/10.1002/cbdv.202300460
  • Tundis, R., Loizzo, M. R., Bonesi, M., Menichini, F., Dodaro, D., Passalacqua, N. G., ... & Menichini, F. (2009). In vitro cytotoxic effects of Senecio stabianus Lacaita (Asteraceae) on human cancer cell lines. Natural Product Research, 23(18), 1707-1718. https://doi.org/10.1080/14786410802194151
  • Türe, C., & Böcük, H. (2010). Distribution patterns of threatened endemic plants in Turkey: A quantitative approach for conservation. Journal for Nature Conservation, 18, 296-303. https://doi.org/10.1016/j.jnc.2010.01.002
  • Uğur, A., Ertem, H., & Beyatlι, Y. (2006). Antibacterial Properties of Senecio sandrasicus on Multidrug-Resistant Stenotrophomonas maltophilia. Pharmaceutical Biology, 44(4), 253-257. https://doi.org/10.1080/13880200600713865
  • Ugur, A., Sarac, N., Duru, M. E., & Beyatli, Y. (2009). In vitro study of antibacterial activity on multi-resistant bacteria and chemical composition of the chloroform extract of endemic Centaurea drabifolia subsp. cappadocica. Natural Product Communications, 4(9), 1934578X0900400922. https://doi.org/10.1177/1934578X0900400922
  • Wang, W. S., Lu, P., Duan, C. H., & Feng, J. C. (2010). A new jacaranone derivative from Senecio scandens var. incisus. Natural Product Research, 24(4), 370-374. https://doi.org/10.1080/14786410903250936
  • Yirtici, Ü., Göger, F., Sarimahmut, M., & Ergene, A. (2017). Cytotoxic and apoptotic effects of endemic Centaurea fenzlii Reichardt on the MCF-7 breast cancer cell line. Turkish Journal of Biology, 41, 370-377. https://doi.org/10.3906/biy-1609-74
  • Zengin, G., Mahoomodally, M. F., Sinan, K. I., Bakar, K., Jugreet, S., Yildiztugay, E., ... & Caprioli, G. (2022). A Comparative Study of Chemical Profiling and Biological Effects of Doronicum orientale Extracts. Chemistry & Biodiversity, 19(4), e202200076. https://doi.org/10.1002/cbdv.202200076
  • Zengin, G., Zheleva-Dimitrova, D., Gevrenova, R., Nedialkov, P., Mocan, A., Ćirić, A., ... & Mahomoodally, M. F. (2018). Identification of phenolic components via LC-MS analysis and biological activities of two Centaurea species: C. drabifolia subsp. drabifolia and C. lycopifolia. Journal of Pharmaceutical and Biomedical Analysis, 149, 436-441. https://doi.org/10.1016/j.jpba.2017.11.045
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Kanser Tedavisi (Kemoterapi ve Radyoterapi hariç)
Bölüm Araştırma Makaleleri
Yazarlar

Mehmet Sarimahmut 0000-0003-2647-5875

Serap Celikler Kasımoğulları 0000-0002-4177-3478

Proje Numarası N/A
Yayımlanma Tarihi 31 Ekim 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 2 Sayı: Kongre Özel Sayısı - 3. Uluslararası Multidisipliner Kanser Araştırmaları Kongresi

Kaynak Göster

APA Sarimahmut, M., & Celikler Kasımoğulları, S. (2023). Antioxidant and Anti-Growth Properties of Selected Anatolian Plant Species: Exploring the Potential of Heracleum humile, Doronicum reticulatum, Centaurea drabifolia, and Senecio olympicus. Doğu Karadeniz Sağlık Bilimleri Dergisi, 2(Kongre Özel Sayısı), 102-111. https://doi.org/10.59312/ebshealth.1366959

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