Gingko biloba L.’nın Fitokimyasal Bileşimi, Antioksidan ve Anti-Kanser Aktiviteleri Üzerine Bir Araştırma

Öz

Çalışma, Ginkgo biloba L. yaprak metanol ekstresinin fitokimyasal bileşimini, antioksidan potansiyelini ve anti-kanser aktivitesini araştırmayı amaçlamaktadır. Bu çalışmada, G. biloba yaprağından elde edilen metanol ekstresinin fitokimyasal bileşikleri, toplam fenolik ve flavonoid içerikleri incelenmiştir. Ayrıca, antioksidan ve anti-kanser [HT-29 (insan kolon kanseri hücre hattı), HeLa (insan rahim ağzı kanseri hücre hattı) ve HEK-293 (insan embriyonik böbrek hücre hattı)] aktiviteleri test edilmiştir. G. biloba yaprak metanol ekstresinin başlıca fitokimyasal bileşikleri HPLC ile gallik asit (0.94±0.01 mg/g), p-hidroksi benzoik asit (0.71±0.01 mg/g) ve protokateşik asit (0.60±0.02 mg/g) olarak belirlenmiştir. Toplam fenolik ve toplam flavonoid içerikleri sırasıyla 71.20±0.42 µg GAE/mg ekstre ve 13.24±0.35 µg QE/mg ekstre olarak ölçülmüştür. 400 µg/mL’de ABTS•+ yönteminde yüksek antioksidan aktivite (%89.04±0.71) belirlenirken, DPPH• (%43.31±0.75), metal kelatlama (%49.04±0.49), CUPRAC (absorbans: 0.85±0.01) ve fosfomolibden (absorbans: 1.16±0.02) yöntemlerinde orta derecede antioksidan aktivite gözlenmiştir. G. biloba yaprak metanol ekstresinin HT-29, HeLa ve HEK-293 hücre hatlarındaki IC50 değerleri sırasıyla 406.70±1.55, 84.86±0.98 ve >800 µg/mL olarak kaydedilmiştir. Bu çalışma, fitokimyasal içeriği ile terapötik açıdan değerli G. biloba’nın antioksidan ve anti-kanser özelliklerine yeni bir katkı sunmaktadır.

Anahtar Kelimeler

• Mabet ağacı
• Metanol ekstresi
• HT-29 hücre hattı
• HeLa hücre hattı
• HPLC
• HEK-293 hücre hattı

A Study on Phytochemical Composition, Antioxidant, and Anti-Cancer Activities of Gingko biloba L.

Öz

The study aims to investigate the phytochemical composition, antioxidant potential, and anti-cancer activities of Ginkgo biloba L. leaf methanol extract. In this study, the phytochemical compounds, total phenolic and flavonoid contents of G. biloba leaf methanol extract were investigated. Additionally, antioxidant and anti-cancer activities [against HT-29 (human colon cancer line), HeLa (human cervical cancer line), and HEK-293 (human embryonic kidney cell line)] were assayed. The main phytochemical compounds were identified as gallic (0.94±0.01 mg/g), p-hydroxy benzoic (0.71±0.01 mg/g), and protocatechuic (0.60±0.02 mg/g) acids in G. biloba leaf methanol extract by HPLC. The total phenolic and total flavonoid contents were measured as 71.20±0.42 µg GAE/mg extract and 13.24±0.35 µg QE/mg extract, respectively. The high antioxidant activity was found in ABTS•+ assay (89.04±0.71%) while moderate antioxidant activity was observed in DPPH• (43.31±0.75%), metal chelating (49.04±0.49%), CUPRAC (absorbance: 0.85±0.01), and phosphomolybdenum (absorbance: 1.16±0.02) assays at 400 µg/mL. The IC50 values of G. biloba leaf methanol extract on HT-29, HeLa, and HEK-293 cell lines were recorded as 406.70±1.55, 84.86±0.98, and >800 µg/mL, respectively. The present study features a new addition to the antioxidant and anti-cancer properties of the therapeutically valuable G. biloba with its phytochemical content.

Anahtar Kelimeler

• Maidenhair tree
• Methanol extract
• HT-29 cell line
• HeLa cell line
• HPLC
• HEK-293 cell line

Kaynakça

1. Abedi, F., Razavi, B.M., & Hosseinzadeh, H. (2020). A review on gentisic acid as a plant derived phenolic acid and metabolite of aspirin: Comprehensive pharmacology, toxicology, and some pharmaceutical aspects. Phytotherapy Research, 34(4), 729-741. https://doi.org/10.1002/ptr.6573
2. Akyildiz, I.E., Raday, S., Erdem, O., Acar, S., Coskun, I., & Damarli, E. (2021). Analytical investigation of active compound contents of Panax ginseng C.A. Meyer and Ginkgo biloba L. supplements fortified with apitherapy products. International Journal of Secondary Metabolite, 8, 70-93. https://dx.doi.org/10.21448/ijsm.832424
3. Alzahrani, S.M., Al Doghaither, H.A., & Al‑Ghafari, A.B. (2021). General insight into cancer: An overview of colorectal cancer (Review). Molecular and Clinical Oncology, 15, 271. https://doi.org/10.3892/mco.2021.2433
4. Aybastier, Ö. (2020). Determination of antioxidant properties of Ginkgo biloba in different forms. European Journal of Science and Technology, 18, 206-212. https://doi.org/10.31590/ejosat.680343.
5. Azeem, M., Hanif, M., Mahmood, K., Ameer, N., Chughtai, F.R.S., & Abid, U. (2023). An insight into anticancer, antioxidant, antimicrobial, antidiabetic and anti-inflammatory effects of quercetin: A review. Polymer Bulletin, 80, 241-262. https://doi.org/10.1007/s00289-022-04091-8
6. Bach, F., Zielinski, A.A.F., Helm, C.V., Maciel, G.M., Pedro, A.C., Stafussa, A.P., … & Haminiuk, C.W.I. (2019). Bio compounds of edible mushrooms: in vitro antioxidant and antimicrobial activities. LWT-Food Science and Technology, 107, 214-220. https://doi.org/10.1016/j.lwt.2019.03.017
7. Baranwal, A., Aggarwal, P., Rai, A., & Kumar, N. (2022). Pharmacological actions and underlying mechanisms of catechin: A review. Mini-Reviews in Medicinal Chemistry, 22, 821-833, https://doi.org/10.2174/1389557521666210902162120
8. Barbalho, S.M., Direito, R., Laurindo, L.F., Marton, L.T., Guiguer, E.L., Goulart, R.A., … & Araujo, A.C. (2022). Ginkgo biloba in the aging process: a narrative review. Antioxidants, 11, 525. https://doi.org/10.3390/antiox11030525

9. Brondino, N., De Silvestri, A., Re, S., Lanati, N., Thiemann, P., Verna, A., … & Politi, P. (2013). A systematic review and meta-analysis of Ginkgo biloba in neuropsychiatric disorders: From ancient tradition to modern-day medicine. Evidence-Based Complementary and Alternative Medicine, 2013, 915691. https://doi.org/10.1155/2013/915691
10. Burmeister, C.A., Khan, S.F., Schäfer, G., Mbatani, N., Adams, T., Moodley, J., & Prince, S. (2022). Cervical cancer therapies: Current challenges and future perspectives. Tumour Virus Research, 13, 200238. https://doi.org/10.1016/j.tvr.2022.200238
11. Çayan, F., Tel-Çayan, G., Deveci, E., Öztürk, M., & Duru, M.E. (2019). Chemical profile, in vitro enzyme inhibitory, and antioxidant properties of Stereum species (Agaricomycetes) from Turkey. International Journal of Medicinal Mushrooms, 21(11), 1075-1087. https://doi.org/10.1615/IntJMedMushrooms.2019032893.
12. Chen, X.H., Miao, Y.X., Wang, X.J., Yu, Z., Geng, M.Y., Han, Y.T., & Wang, L.X. (2011). Effects of Ginkgo biloba extract EGb761 on human colon adenocarcinoma cells. Cellular Physiology & Biochemistry, 27(3-4), 227-232. https://doi.org/10.1159/000327948.
13. Demir, T., & Akpınar, Ö. (2020). Biological activities of phytochemicals in plants. Turkish Journal of Agriculture-Food Science and Technology, 8(8), 1734-1746.
14. El-Beltagi, H.S., & Badawi, M.H. (2013). Comparison of antioxidant and antimicrobial properties for Ginkgo biloba and Rosemary (Rosmarinus officinalis L.) from Egypt. Notulae Botanicae Horti Agrobotanici Cluj-Napoca, 41(1), 126-135. https://doi.org/10.15835/nbha4118928
15. Hossain, M.S., Karuniawati, H., Jairoun, A.A., Urbi, Z., Ooi, D.J., John, A., … & Hadi, M.A. (2022). Colorectal cancer: A review of carcinogenesis, global epidemiology, current challenges, risk factors, preventive and treatment strategies. Cancers (Basel), 14(7), 1732. https://doi.org/10.3390/cancers14071732
16. Hu, W.H., Chan, G.K.L., Duan, R., Wang, H.Y., Kong, X.P., Dong, T.T.X., & Tsim, K.W.K. (2019). Synergy of ginkgetin and resveratrol in suppressing VEGF-induced angiogenesis: A therapy in treating colorectal cancer. Cancers, 11(12), 1828. https://doi.org/10.3390/cancers11121828
17. Hull, R., Mbele, M., Makhafola, T., Hicks, C., Wang, S.M., Reis, R.M., … & Dlamini, Z. (2020). Cervical cancer in low and middle‑income countries (Review). Oncology Letters, 20(3), 2058-2074. https://doi.org/10.3892/ol.2020.11754
18. Jain, H. (2015). The medicinal value and the numerous sources of vitamin c-a review. Journal of Nutritional Health & Food Engineering, 2(4), 124-134. https://doi.org/10.15406/jnhfe.2015.02.00061.
19. Kakkar, S., & Bais, S. (2014). A review on protocatechuic acid and its pharmacological potential. International Scholarly Research Notices, 2014, 952943. https://doi.org/10.1155/2014/952943
20. Karabulut, G., & Yemiş, O. (2019). Bound forms of phenolic compounds and their bioavailability. Akademik Gıda, 17(4), 526-537. https://doi.org/10.24323/akademik-gida.667270
21. Kaur, P., Chaudhary, A., Singh, B., & Gopichand. (2012). An efficient microwave assisted extraction of phenolic compounds and antioxidant potential of Ginkgo biloba. Natural Product Communications, 7, 203-206. https://doi.org/10.1177/1934578X1200700222
22. Kim, S.H., & Yim, S.H. (2022). Effects of bilobol from the fruit pulp of Ginkgo biloba on cell viability. Food Science and Technology, 42, e57522. https://doi.org/10.1590/fst.57522.
23. Kiokias, S., Proestos, C., & Oreopoulou, V. (2020). Phenolic acids of plant origin-a review on their antioxidant activity in vitro (O/W emulsion systems) along with their in vivo health biochemical properties. Foods, 9(4), 534. https://doi.org/10.3390/foods9040534
24. Klomsakul, P., Aiumsubtub, A., & Chalopagorn, P. (2022). Evaluation of antioxidant activities and tyrosinase inhibitory effects of Ginkgo biloba tea extract. The Scientific World Journal, 2022, 4806889. https://doi.org/10.1155/2022/4806889.
25. Kobus, J., Flaczyk, E., Siger, A., Nogala-Kalucka, M., Korczak, J., & Pegg, R.B. (2009). Phenolic compounds and antioxidant activity of extracts of Ginkgo leaves. European Journal of Lipid Science and Technology, 111, 1150-1160. https://doi.org/10.1002/ejlt.200800299
26. Les, F., Casedas, G., & Lopez, V. (2021). Bioactivity of medicinal plants and extracts. Biology, 10, 634. https://doi.org/10.3390/biology10070634.
27. Li, L., Zhang, M.X., Wang, X.Y., Yang, Y.L., Gong, X., Wang, C.C., … & Li, M.H. (2021). Assessment of components of Gingko biloba leaves collected from different regions of China that contribute to its antioxidant effects for improved quality monitoring. Food Sciences and Technology (Campinas), 41(Suppl.2), 676-683. https://doi.org/10.1590/fst.33620
28. Li, M., Li, B., Xia, Z.M., Tian, Y., Zhang, D., Rui, W.R., … & Xiao, F.J. (2019). Anticancer effects of five biflavonoids from Ginkgo biloba L. male flowers in vitro. Molecules, 24, 1496. https://doi.org/10.3390/molecules24081496
29. Lin, X., Wang, G., Liu, P., Han, L., Wang, T., Chen, K., & Gao, Y. (2021). Gallic acid suppresses colon cancer proliferation by inhibiting SRC and EGFR phosphorylation. Experimental and Therapeutic Medicine, 21(6), 638. https://doi.org/10.3892/etm.2021.10070
30. Liu, Y., Yang, B., Zhang, L., Cong, X., Liu, Z., Hu, Y., & Hu, H. (2018). Ginkgolic acid induces interplay between apoptosis and autophagy regulated by ROS generation in colon cancer. Biochemical and Biophysical Research Communications, 498, 246-253. https://doi.org/10.1016/j.bbrc.2018.01.091
31. Malik, A., Khatkar, A., & Kakkar, S. (2023). A review on pharmacological activities of vanillic acid and its derivatives. Indo Global Journal of Pharmaceutical Sciences, 13, 1-12.
32. Maltas, E., Vural, H.C., & Yildiz, S. (2011). Antioxidant activity and fatty acid composition of Ginkgo biloba from Turkey. Journal of Food Biochemistry, 35(3), 803-818. https://doi.org/10.1111/j.1745-4514.2010.00418.x
33. Manuja, R., Sachdeva, S., Jain, A., & Chaudhary, J. (2013). A comprehensive review on biological activities of p-hydroxy benzoic acid and its derivatives. International Journal of Pharmaceutical Sciences Review and Research, 22(2), 109-115.
34. Munteanu, I.G., & Apetrei, C. (2021). Analytical methods used in determining antioxidant activity: a review. International Journal of Molecular Sciences, 22(7), 3380. https://doi.org/10.3390/ijms22073380
35. Pang, S.S., Murphy, M., & Markham, M.J. (2022). Current management of locally advanced and metastatic cervical cancer in the United States. JCO Oncology Practice, 18, 417-422. https://doi.org/10.1200/OP.21.00795
36. 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.
37. Pereira, E., Barros, L., & Ferreira, I.C.F.R. (2013). Chemical characterization of Ginkgo biloba L. and antioxidant properties of its extracts and dietary supplements. Industrial Crops and Products, 51, 244-248. https://doi.org/10.1016/j.indcrop.2013.09.011.
38. Prieto, P., Pineda, M., & Aguilar, M. (1999). Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. Analytical Biochemistry, 269, 337-341. https://doi.org/10.1006/abio.1999.4019
39. Pyrzynska, K. (2022). Hesperidin: A review on extraction methods, stability and biological activities. Nutrients, 14, 2387. https://doi.org/10.3390/nu14122387.
40. Ruwizhi, N., & Aderibigbe, B.A. (2020). Cinnamic acid derivatives and their biological efficacy. International Journal of Molecular Sciences, 21, 5712. https://doi.org/10.3390/ijms21165712
41. Sawicki, T., Ruszkowska, M., Danielewicz, A., Niedzwiedzka, E., Arlukowicz, T., & Przybylowicz, K.E. (2021). A review of colorectal cancer in terms of epidemiology, risk factors, development, symptoms and diagnosis. Cancers, 13(9), 2025. https://doi.org/10.3390/cancers13092025
42. Shu, P., Sun, M., Li, J., Zhang, L., & Xu, H. (2020). Chemical constituents from Ginkgo biloba leaves and their cytotoxicity activity. Journal of Natural Medicines, 74, 269-274. https://doi.org/10.1007/s11418-019-01359-8.
43. Slinkard, K., & Singleton, V.L. (1977). Total phenol analyses: Automation and comparison with manual methods. American Journal of Enology and Viticulture, 28, 49-55. https://doi.org/10.5344/ajev.1977.28.1.49
44. Srikrishna, D., Godugu, C., & Dubey, P.K. (2018). A review on pharmacological properties of coumarins. Mini-Reviews in Medicinal Chemistry, 18, 113-141. https://doi.org/10.2174/1389557516666160801094919
45. Szewczyk, A., Kwiecien, I., Grabowski, M., Rajek, K., Cavo, E., Taviano, M.F., & Miceli, N. (2021). Phenylalanine increases the production of antioxidant phenolic acids in Ginkgo biloba cell cultures. Molecules, 26, 4965. https://doi.org/10.3390/molecules26164965
46. Tabassum, N.E., Das, R., Lami, M.S., Chakraborty, A.J., Mitra, S., Tallei, T.E., … & Emran, T.B. (2022). Ginkgo biloba: A treasure of functional phytochemicals with multimedicinal applications. Evidence-Based Complementary and Alternative Medicine, 2022, 8288818. https://doi.org/10.1155/2022/8288818
47. Tiwari, R., & Shukla, A.K. (2020). Plant metabolites and their role in health benefits: A brief review. Advance Pharmaceutical Journal, 5(2), 47-53. https://doi.org/10.31024/apj.2020.5.2.2
48. Wang, Y., Li, X., Lv, H., Sun, L., Liu, B., Zhang, X., & Xu, X. (2023). Therapeutic potential of naringin in improving the survival rate of skin flap: A review. Frontiers in Pharmacology, 14, 1128147. https://doi.org/10.3389/fphar.2023.1128147
49. Xu, Y., Ma, Q., Chen, D., Yin, Q., & Zhang, W. (2020). Effects of ginkgolide B on the proliferation and apoptosis of cervical cancer cells. Current Topics in Nutraceutical Research, 18, 227-232. https://doi.org/10.37290/ctnr2641-452x.18:227-232
50. 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
51. You, B.R, Moon, H.J., Han, Y.H., & Park, W.H. (2010). Gallic acid inhibits the growth of HeLa cervical cancer cells via apoptosis and/or necrosis. Food and Chemical Toxicology, 48(5), 1334-1340. https://doi.org/10.1016/j.fct.2010.02.034
52. Zhang, L.X., Li, C.X., Kakar, M.U., Khan, M.S., Wu, P.F., Amir, R.M., … & Li, J.H. (2021). Resveratrol (RV): A pharmacological review and call for further research. Biomedicine & Pharmacotherapy, 143, 112164. https://doi.org/10.1016/j.biopha.2021.112164
53. Zheng, W., & Wang, S.Y. (2001). Antioxidant activity and phenolic compounds in selected herbs. Journal of Agricultural and Food Chemistry, 49, 5165-5170. https://doi.org/10.1021/jf010697n