Evaluation of the in vitro enzyme inhibition and antioxidant activity of Clinopodium betulifolium (Boiss. & Balansa) Kuntze
Öz
Clinopodium betulifolium (Boiss. & Balansa) Kuntze is a perennial herb belonging to the Lamiaceae family. There are few studies on C. betulifolium, except for its essential oil. In this study, Alzheimer's and cosmetic-related enzyme inhibitory activity and antioxidant activity of C. betulifolium species were evaluated. This study extracted C. betulifolium aerial parts by maceration using 70% methanol and water. Antioxidant [DPPH scavenging assay, ABTS cation decolorization, and iron chelating activity] and enzyme inhibition (acetyl-, and butyrylcholine esterase, and tyrosinase) activities of C. betulifolium extracts were evaluated using Elisa microplate reader at 2 mg mL-1 stock concentration. C. betulifolium aqueous extract gave high antioxidant activity (IC50: 34.24 ± 5.01 µg mL-1) in the ABTS method, while its 70% methanol extract (IC50: 100.75 ± 2.62 µg mL-1) was higher than the aqueous extract (IC50: 131.83 ± 4.70 µg mL-1) in the DPPH method. C. betulifolium aqueous and 70% methanol extract have moderate anti-tyrosinase activity. Both 70% methanol and aqueous extracts showed similar and high activity against acetylcholinesterase with the IC50 values of 73.94 ± 2.78 µg mL-1 and 81.71 ± 9.38 µg mL-1, respectively. C. betulifolium 70% methanol extract (IC50: 64.08 ± 1.04 µg mL-1) showed higher inhibitory activity than the aqueous extract (IC50: 146.6 ± 8.27 µg mL-1) against butyrylcholinesterase. These results provide basic information for studies that will yield positive results in the development of pharmaceutical formulations or food supplements to be used to treat Alzheimer's and oxidative stress-related diseases.
Anahtar Kelimeler
Clinopodium betulifolium Anti-cholinesterase Anti-tyrosinase Antioxidant activity
Kaynakça
- Ayla, K. (2017). Morphological characteristics of two endemic subspecies of Clinopodium troodi (Post) Govaerts (Lamiaceae) growing in Turkey. Marmara Pharm. J., 21(3), 493-499.
- Beddiar, H., Boudiba, S., Benahmed, M., Tamfu, A. N., Ceylan, Ö., Hanini, K., Kucukaydin, S., Elomri, A., Bensouici, C., & Laouer, H. (2021). Chemical composition, anti-quorum sensing, enzyme inhibitory, and antioxidant properties of phenolic extracts of Clinopodium nepeta L. Kuntze. Plants, 10(9), 1955.
- Bektašević, M., Politeo, O., Roje, M., & Jurin, M. (2022). Polyphenol Composition, Anticholinesterase and Antioxidant Potential of the Extracts of Clinopodium vulgare L. Chem. Biodivers., e202101002.
- Benites, J., Ríos, D., Guerrero-Castilla, A., Enríquez, C., Zavala, E., Ybañez-Julca, R. O., Quispe-Díaz, I., Jara-Aguilar, R., & Calderon, P. B. (2021). Chemical Composition and Assessment of Antimicrobial, Antioxidant and Antiproliferative Activities of Essential oil from Clinopodium sericeum, a Peruvian Medicinal Plant. Rec. Nat. Prod., 15(3), 175 - 186.
- Chai, T., Mohan, M., Ong, H., & Wong, F. (2014). Antioxidant, iron-chelating and anti-glucosidase activities of Typha domingensis Pers (Typhaceae). Trop. J. Pharm. Res., 13(1), 67-72.
- Clarke, G., Ting, K. N., Wiart, C., & Fry, J. (2013). High correlation of 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing activity potential and total phenolics content indicates redundancy in use of all three assays to screen for antioxidant activity of extracts of plants from the Malaysian rainforest. Antioxidants, 2(1), 1-10.
- De la Torre, L., Navarrete, H., Muriel, P., Macía, M. J., & Balslev, H. (2008). Enciclopedia de las Plantas Útiles del Ecuador (con extracto de datos): Herbario QCA de la Escuela de Ciencias Biológicas de la Pontificia
- Dzhambazov, B., Daskalova, S., Monteva, A., & Popov, N. (2002). In vitro screening for antitumour activity of Clinopodium vulgare L. (Lamiaceae) extracts. Biol. Pharm. Bull., 25(4), 499-504.
- El-Sayed, M. M., Abdel-Hameed, E.-S. S., Ahmed, W. S., & El-Wakil, E. A. (2008). Non-phenolic antioxidant compounds from Buddleja asiatica. Z. Naturforsch. C, 63(7-8), 483-491.
- Ellman, G. L., Courtney, K. D., Andres Jr, V., & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 7(2), 88-95.
- Erdogan Orhan, I., Senol, F. S., Aslan Erdem, S., Tatli, I. I., Kartal, M., & Alp, S. (2015). Tyrosinase and cholinesterase inhibitory potential and flavonoid characterization of Viola odorata L.(Sweet Violet). Phytother Res, 29(9), 1304-1310.
- Fernández-Galleguillos, C., Jiménez-Aspee, F., Mieres-Castro, D., Rodríguez-Núñez, Y. A., Gutiérrez, M., Guzmán, L., Echeverría, J., Sandoval-Yañez, C., & Forero-Doria, O. (2023). Phenolic Profile and Cholinesterase Inhibitory Properties of Three Chilean Altiplano Plants: Clinopodium gilliesii (Benth.) Kuntze [Lamiaceae], Mutisia acuminata Ruiz & Pav. var. hirsuta (Meyen) Cabrera, and Tagetes multiflora (Kunth)[Asteraceae]. Plants, 12(4), 819.
- Gulcin, İ. (2020). Antioxidants and antioxidant methods: An updated overview. Arch. Toxicol., 94(3), 651-715. Güçlü G, Ergül M, Uçar E, Eruygur N, Ataş M, Akpulat HA 2022. Anticancer, Antioxidant, Antimicrobial and Enzyme Inhibitory Activities of Inula aucheriana. KSU J. Agric Nat 25(5), 946-954.
- Kadereit, J. W. (2004). Flowering Plants• Dicotyledons: Lamiales (except Acanthaceae including Avicenniaceae) (Vol. 7), Springer Science & Business Media.
- Kizilarslan, H.Ç., & Özhatay, N. (2012). Wild plants used as medicinal purpose in the south part of İzmit (Northwest Turkey). Turk J. Pharm. Sci, 9(2), 199-218.
- Koçyiğit, Ü.M., Eruygur, N., Ataş, M., Tekin, M., Taslimi, P., Gökalp, F., Gülçin, İ 2022. Evaluation of Anticholinergic, Antidiabetic and Antioxidant Activity of Astragalus dumanii, an Endemic Plant. KSU J. Agric Nat 25 (Suppl 1), 1-10.
- Kürkçüoglu, M., Iscan, G., Ozek, T., Baser, K., & Alan, S. (2007). Composition and antimicrobial activity of the essential oils of Calamintha betulifolia Boiss. et Bal. J. Essent. Oil Res., 19(3), 285-287.
- Na, M.K., Thuong, P. T., & Bae, K.H. (2011). Natural compounds with antioxidant activity: recent findings from studies on medicinal plants. Nat. Prod. Sci., 17(2), 65-79.
- Noriega, P., Calderón, L., Ojeda, A., & Paredes, E. (2023). Chemical Composition, Antimicrobial and Antioxidant Bioautography Activity of Essential Oil from Leaves of Amazon Plant Clinopodium brownei (Sw.). Molecules, 28(4), 1741.
- Noriega, P. F., Mosquera, T. D. L. Ã., Osorio, E. A., Guerra, P., & Fonseca, A. (2018). Clinopodium nubigenum (Kunth) Kuntze essential oil: Chemical composition, antioxidant activity, and antimicrobial test against respiratory pathogens. J. Pharmacogn. Phytotherapy, 10(9), 149-157.
- Qian, W., Liu, W., Zhu, D., Cao, Y., Tang, A., Gong, G., & Su, H. (2020). Natural skin‑whitening compounds for the treatment of melanogenesis. Exp. Ther. Med., 20(1), 173-185.
- 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 Radic. Biol. Med., 26(9-10), 1231-1237.
- Sargin, S. A. (2015). Ethnobotanical survey of medicinal plants in Bozyazı district of Mersin, Turkey. J. Ethnopharmacol., 173, 105-126.
- Sarikurkcu, C., Ozer, M. S., Tepe, B., Dilek, E., & Ceylan, O. (2015). Phenolic composition, antioxidant and enzyme inhibitory activities of acetone, methanol and water extracts of Clinopodium vulgare L. subsp. vulgare L. Ind Crops Prod, 76, 961-966.
- SatIl, F., Kaya, A., & Dirmenci, T. (2011). The taxonomic value of leaf anatomy and trichome morphology of the genus Cyclotrichium (Lamiaceae) in Turkey. Nord. J. Bot., 29(1), 38-48.
- Selvi, S., Polat, R., Çakilcioğlu, U., Celep, F., Dirmenci, T., & Ertug, Z. F. (2022). An ethnobotanical review on medicinal plants of the Lamiaceae family in Turkey. Turk. J. Bot., 46(4), 283-332.
- Sevim, A., & Atila, O. (2009). Taxonomical and morphological studies on the genus Calamintha Miller Lamiaceae in Turkey. Biodivers. Conserv., 2(2), 125-143.
- Šinko, G., Čalić, M., Bosak, A., & Kovarik, Z. (2007). Limitation of the Ellman method: Cholinesterase activity measurement in the presence of oximes. Anal. Biochem., 370(2), 223-227.
- Tepe, B., Sihoglu-Tepe, A., Daferera, D., Polissiou, M., & Sokmen, A. (2007). Chemical composition and antioxidant activity of the essential oil of Clinopodium vulgare L. Food Chem., 103(3), 766-770.
- Tubon, I., Bernardini, C., Antognoni, F., Mandrioli, R., Potente, G., Bertocchi, M., Vaca, G., Zannoni, A., Salaroli, R., & Forni, M. (2020). Clinopodium tomentosum (Kunth) Govaerts leaf extract influences in vitro cell proliferation and angiogenesis on primary cultures of porcine aortic endothelial cells. Oxid. Med. Cell. Longev., 2020, 1-11.
- Yang, H., Dong, Y., Du, H., Shi, H., Peng, Y., & Li, X. (2011). Antioxidant compounds from propolis collected in Anhui, China. Molecules, 16(4), 3444-3455.
- Yang, Z., Wang, Y., Wang, Y., & Zhang, Y. (2012). Bioassay-guided screening and isolation of α-glucosidase and tyrosinase inhibitors from leaves of Morus alba. Food Chem., 131(2), 617-625.
- Yao, L., Li-Min, L., Yuan-Gen, X., Xue-Bin, S., Huan, L., & Si-Hui, N. (2020). Research progress on genus Clinopodium. China Journal of Chinese Materia Medica, 45(18), 4349-4357.
- Zeng, B., Chen, K., Du, P., Wang, S. S., Ren, B., Ren, Y. L., Yan, H. S., Liang, Y., & Wu, F. H. (2016). Phenolic Compounds from Clinopodium chinense (Benth.) O. Kuntze and Their Inhibitory Effects on α‐Glucosidase and Vascular Endothelial Cells Injury. Chem. Biodivers., 13(5), 596-601.
Clinopodium betulifolium (Boiss. & Balansa) Kuntze'nin in vitro enzim inhibisyonu ve antioksidan aktivitesinin değerlendirilmesi
Öz
Clinopodium betulifolium (Boiss. & Balansa) Kuntze, Lamiaceae familyasına ait çok yıllık bir bitkidir. C. betulifolium üzerine uçucu yağı dışında pek fazla çalışma bulunmamaktadır. Bu çalışmada C. betulifolium türünün Alzheimer ve kozmetikle ilişkili enzim inhibitör aktivitesi ve antioksidan aktivitesi değerlendirildi. Bu çalışmada C. betulifolium'un toprak üstü kısımlarından %70 metanol ve su kullanılarak maserasyon tekniği ile ekstraksiyon işlemi yapıldı. C. betulifolium ekstrelerinin antioksidan [DPPH radikal süpürücü aktivite, ABTS katyonik renk giderici ve demir şelatlama aktivitesi] ve enzim inhibisyonu (asetil/bütirilkolinesteraz ve tirozinaz) aktiviteleri, 2 mg mL-1 stok konsantrasyonunda Elisa mikroplaka okuyucusu kullanılarak değerlendirildi. C. betulifolium su ekstresi ABTS yönteminde yüksek antioksidan aktivite verirken (IC50: 34.24 ± 5.01 µg mL-1), DPPH yönteminde %70 metanol ekstresi (IC50: 100.75 ± 2.62 µg mL-1) sulu ekstresinden (IC50: 131,83 ± 4,70 µg mL-1) daha yüksek aktivitede bulunmuştur. C. betulifolium su ve %70 metanol ekstreleri orta derecede anti-tirozinaz aktivitesine sahiptir. Hem %70 metanol hem de su ekstreleri sırasıyla 73,94 ± 2,78 µg mL-1 ve 81,71 ± 9,38 µg mL-1 IC50 değerleriyle asetilkolinesteraza karşı benzer ve yüksek aktivite gösterdi. C. betulifolium %70 metanol ekstresi (IC50: 64,08 ± 1,04 µg mL-1), bütirilkolinesteraza karşı su ekstresinden (IC50: 146,6 ± 8,27 µg mL-1) daha yüksek inhibitör aktivite gösterdi. Bu sonuçlar Alzheimer ve oksidatif strese bağlı hastalıkların tedavisinde kullanılacak farmasötik formülasyonların veya gıda takviyelerinin geliştirilmesinde olumlu sonuçlar verecek çalışmalar için temel bilgiler sağlamaktadır.
Anahtar Kelimeler
Clinopodium betulifolium Antikolinesteraz Anti-tirozinaz Antioksidan aktivite
Destekleyen Kurum
Selçuk Üniversitesi Bilimsel Araştırmalar Koordinatörlüğü
Teşekkür
Bu çalışmanın gercekleşmesinde maddi imkan sağlayan Selçuk Üniversitesi. Bilimsel Araştırma Projeleri (BAP) birimine katkılarından dolayı teşekkür ederiz.
Kaynakça
- Ayla, K. (2017). Morphological characteristics of two endemic subspecies of Clinopodium troodi (Post) Govaerts (Lamiaceae) growing in Turkey. Marmara Pharm. J., 21(3), 493-499.
- Beddiar, H., Boudiba, S., Benahmed, M., Tamfu, A. N., Ceylan, Ö., Hanini, K., Kucukaydin, S., Elomri, A., Bensouici, C., & Laouer, H. (2021). Chemical composition, anti-quorum sensing, enzyme inhibitory, and antioxidant properties of phenolic extracts of Clinopodium nepeta L. Kuntze. Plants, 10(9), 1955.
- Bektašević, M., Politeo, O., Roje, M., & Jurin, M. (2022). Polyphenol Composition, Anticholinesterase and Antioxidant Potential of the Extracts of Clinopodium vulgare L. Chem. Biodivers., e202101002.
- Benites, J., Ríos, D., Guerrero-Castilla, A., Enríquez, C., Zavala, E., Ybañez-Julca, R. O., Quispe-Díaz, I., Jara-Aguilar, R., & Calderon, P. B. (2021). Chemical Composition and Assessment of Antimicrobial, Antioxidant and Antiproliferative Activities of Essential oil from Clinopodium sericeum, a Peruvian Medicinal Plant. Rec. Nat. Prod., 15(3), 175 - 186.
- Chai, T., Mohan, M., Ong, H., & Wong, F. (2014). Antioxidant, iron-chelating and anti-glucosidase activities of Typha domingensis Pers (Typhaceae). Trop. J. Pharm. Res., 13(1), 67-72.
- Clarke, G., Ting, K. N., Wiart, C., & Fry, J. (2013). High correlation of 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing activity potential and total phenolics content indicates redundancy in use of all three assays to screen for antioxidant activity of extracts of plants from the Malaysian rainforest. Antioxidants, 2(1), 1-10.
- De la Torre, L., Navarrete, H., Muriel, P., Macía, M. J., & Balslev, H. (2008). Enciclopedia de las Plantas Útiles del Ecuador (con extracto de datos): Herbario QCA de la Escuela de Ciencias Biológicas de la Pontificia
- Dzhambazov, B., Daskalova, S., Monteva, A., & Popov, N. (2002). In vitro screening for antitumour activity of Clinopodium vulgare L. (Lamiaceae) extracts. Biol. Pharm. Bull., 25(4), 499-504.
- El-Sayed, M. M., Abdel-Hameed, E.-S. S., Ahmed, W. S., & El-Wakil, E. A. (2008). Non-phenolic antioxidant compounds from Buddleja asiatica. Z. Naturforsch. C, 63(7-8), 483-491.
- Ellman, G. L., Courtney, K. D., Andres Jr, V., & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 7(2), 88-95.
- Erdogan Orhan, I., Senol, F. S., Aslan Erdem, S., Tatli, I. I., Kartal, M., & Alp, S. (2015). Tyrosinase and cholinesterase inhibitory potential and flavonoid characterization of Viola odorata L.(Sweet Violet). Phytother Res, 29(9), 1304-1310.
- Fernández-Galleguillos, C., Jiménez-Aspee, F., Mieres-Castro, D., Rodríguez-Núñez, Y. A., Gutiérrez, M., Guzmán, L., Echeverría, J., Sandoval-Yañez, C., & Forero-Doria, O. (2023). Phenolic Profile and Cholinesterase Inhibitory Properties of Three Chilean Altiplano Plants: Clinopodium gilliesii (Benth.) Kuntze [Lamiaceae], Mutisia acuminata Ruiz & Pav. var. hirsuta (Meyen) Cabrera, and Tagetes multiflora (Kunth)[Asteraceae]. Plants, 12(4), 819.
- Gulcin, İ. (2020). Antioxidants and antioxidant methods: An updated overview. Arch. Toxicol., 94(3), 651-715. Güçlü G, Ergül M, Uçar E, Eruygur N, Ataş M, Akpulat HA 2022. Anticancer, Antioxidant, Antimicrobial and Enzyme Inhibitory Activities of Inula aucheriana. KSU J. Agric Nat 25(5), 946-954.
- Kadereit, J. W. (2004). Flowering Plants• Dicotyledons: Lamiales (except Acanthaceae including Avicenniaceae) (Vol. 7), Springer Science & Business Media.
- Kizilarslan, H.Ç., & Özhatay, N. (2012). Wild plants used as medicinal purpose in the south part of İzmit (Northwest Turkey). Turk J. Pharm. Sci, 9(2), 199-218.
- Koçyiğit, Ü.M., Eruygur, N., Ataş, M., Tekin, M., Taslimi, P., Gökalp, F., Gülçin, İ 2022. Evaluation of Anticholinergic, Antidiabetic and Antioxidant Activity of Astragalus dumanii, an Endemic Plant. KSU J. Agric Nat 25 (Suppl 1), 1-10.
- Kürkçüoglu, M., Iscan, G., Ozek, T., Baser, K., & Alan, S. (2007). Composition and antimicrobial activity of the essential oils of Calamintha betulifolia Boiss. et Bal. J. Essent. Oil Res., 19(3), 285-287.
- Na, M.K., Thuong, P. T., & Bae, K.H. (2011). Natural compounds with antioxidant activity: recent findings from studies on medicinal plants. Nat. Prod. Sci., 17(2), 65-79.
- Noriega, P., Calderón, L., Ojeda, A., & Paredes, E. (2023). Chemical Composition, Antimicrobial and Antioxidant Bioautography Activity of Essential Oil from Leaves of Amazon Plant Clinopodium brownei (Sw.). Molecules, 28(4), 1741.
- Noriega, P. F., Mosquera, T. D. L. Ã., Osorio, E. A., Guerra, P., & Fonseca, A. (2018). Clinopodium nubigenum (Kunth) Kuntze essential oil: Chemical composition, antioxidant activity, and antimicrobial test against respiratory pathogens. J. Pharmacogn. Phytotherapy, 10(9), 149-157.
- Qian, W., Liu, W., Zhu, D., Cao, Y., Tang, A., Gong, G., & Su, H. (2020). Natural skin‑whitening compounds for the treatment of melanogenesis. Exp. Ther. Med., 20(1), 173-185.
- 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 Radic. Biol. Med., 26(9-10), 1231-1237.
- Sargin, S. A. (2015). Ethnobotanical survey of medicinal plants in Bozyazı district of Mersin, Turkey. J. Ethnopharmacol., 173, 105-126.
- Sarikurkcu, C., Ozer, M. S., Tepe, B., Dilek, E., & Ceylan, O. (2015). Phenolic composition, antioxidant and enzyme inhibitory activities of acetone, methanol and water extracts of Clinopodium vulgare L. subsp. vulgare L. Ind Crops Prod, 76, 961-966.
- SatIl, F., Kaya, A., & Dirmenci, T. (2011). The taxonomic value of leaf anatomy and trichome morphology of the genus Cyclotrichium (Lamiaceae) in Turkey. Nord. J. Bot., 29(1), 38-48.
- Selvi, S., Polat, R., Çakilcioğlu, U., Celep, F., Dirmenci, T., & Ertug, Z. F. (2022). An ethnobotanical review on medicinal plants of the Lamiaceae family in Turkey. Turk. J. Bot., 46(4), 283-332.
- Sevim, A., & Atila, O. (2009). Taxonomical and morphological studies on the genus Calamintha Miller Lamiaceae in Turkey. Biodivers. Conserv., 2(2), 125-143.
- Šinko, G., Čalić, M., Bosak, A., & Kovarik, Z. (2007). Limitation of the Ellman method: Cholinesterase activity measurement in the presence of oximes. Anal. Biochem., 370(2), 223-227.
- Tepe, B., Sihoglu-Tepe, A., Daferera, D., Polissiou, M., & Sokmen, A. (2007). Chemical composition and antioxidant activity of the essential oil of Clinopodium vulgare L. Food Chem., 103(3), 766-770.
- Tubon, I., Bernardini, C., Antognoni, F., Mandrioli, R., Potente, G., Bertocchi, M., Vaca, G., Zannoni, A., Salaroli, R., & Forni, M. (2020). Clinopodium tomentosum (Kunth) Govaerts leaf extract influences in vitro cell proliferation and angiogenesis on primary cultures of porcine aortic endothelial cells. Oxid. Med. Cell. Longev., 2020, 1-11.
- Yang, H., Dong, Y., Du, H., Shi, H., Peng, Y., & Li, X. (2011). Antioxidant compounds from propolis collected in Anhui, China. Molecules, 16(4), 3444-3455.
- Yang, Z., Wang, Y., Wang, Y., & Zhang, Y. (2012). Bioassay-guided screening and isolation of α-glucosidase and tyrosinase inhibitors from leaves of Morus alba. Food Chem., 131(2), 617-625.
- Yao, L., Li-Min, L., Yuan-Gen, X., Xue-Bin, S., Huan, L., & Si-Hui, N. (2020). Research progress on genus Clinopodium. China Journal of Chinese Materia Medica, 45(18), 4349-4357.
- Zeng, B., Chen, K., Du, P., Wang, S. S., Ren, B., Ren, Y. L., Yan, H. S., Liang, Y., & Wu, F. H. (2016). Phenolic Compounds from Clinopodium chinense (Benth.) O. Kuntze and Their Inhibitory Effects on α‐Glucosidase and Vascular Endothelial Cells Injury. Chem. Biodivers., 13(5), 596-601.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Eczacılık ve İlaç Bilimleri (Diğer) |
| Bölüm | ARAŞTIRMA MAKALESİ (Research Article) |
| Yazarlar | |
| Erken Görünüm Tarihi | 15 Ağustos 2024 |
| Yayımlanma Tarihi | 7 Kasım 2024 |
| Gönderilme Tarihi | 12 Aralık 2023 |
| Kabul Tarihi | 22 Nisan 2024 |
| Yayımlandığı Sayı | Yıl 2024 |
Kaynak Göster
2022-JIF = 0.500
2022-JCI = 0.170
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