DESMANTHUS VİRGATUS (L.) YAPRAKLARININ ETANOL EKSTRESİ ÜZERİNE İN SİLİKO VE İN VİTRO ANTİDİYABETİK AKTİVİTE ÇALIŞMALARI

Öz

Amaç: Bu çalışma, in siliko ve in vitro (α-glukozidaz inhibisyonu) yöntemlerle D. virgatus bitkisinin yapraklardan elde edilen etanol ekstresinin antidiyabetik etki potansiyelini belirlemeyi amaçlamaktadır. Gereç ve Yöntem: LC-MS kullanılarak D. virgatus yapraklarının etanol ekstresindeki bileşikler tanımlanmıştır. Antidiyabetik aktivite in silico ve in vitro olarak belirlenmiştir. Sonuç ve Tartışma: Kullanılan protein kodu (PDB ID) 3AJ7 ve 3W37'dir, daha sonra akarboz pozitif kontrol olarak kullanılmıştır. LC-MS kullanılarak ekstrakttan 160 bileşik tanımlanmıştır. Tanımlanan bileşiklerin tümü silikoda test edilmiş, 3AJ7 proteini kullanılarak 18 bileşik ve 3W37 ile 10 bileşiğin Lipinski'nin kuralını 3A37 proteini için ≤ -8.2 kcal/mol ve 3W37 için ≤ -8.1 kcal/mol bağlanma afinite değeri ile karşıladığı bulunmuştur, bu da akarboza benzerdir. Ayrıca, ekstre ve akarbozun α-glukozidaz inhibitörü etkisi in vitro olarak test edilmiştir, elde edilen IC50 değeri sırasıyla 144.11 ppm'dir ve 3.78 ppm'dir. Ekstrenin etkisi orta kategoriye sokulabilir.

Anahtar Kelimeler

• Antidiyabetik
• Desmanthus virgatus
• etanol ekstresi
• in siliko
• in vitro

IN SILICO AND IN VITRO ANTIDIABETIC ACTIVITY STUDIES ON THE ETHANOL EXTRACT OF DESMANTHUS VIRGATUS (L.) LEAVES

Öz

Objective: In vitro and in silico studies using α-glucosidase activity inhibition aimed at identifying the potential antidiabetic properties of ethanol extracts of D. virgatus leaves. Material and Method: Compounds in the ethanol extract of D. virgatus leaves were identified by LC-MS. In vitro and in silico methods were used to determine the antidiabetic activity. Result and Discussion: The protein code (PDB ID) used is 3AJ7 and 3W37, then acarbose was used as a positive control. By using LC-MS,160 compounds were identified from the extract. All of the identified compounds were tested in silico, using 3AJ7 protein 18 compounds and with 3W37 10 compounds were found to fulfill Lipinski's rule with a binding affinity value ≤ -8.2 kcal/mol for 3A37 protein and ≤ -8.1 kcal/mol for 3W37, which is similar to acarbose. In addition, α-glucosidase inhibition was used to assess the antidiabetic effect of the ethanol extract of D. virgatus leaves in vitro, resulting in IC50 values of 144.11 ppm for the extract and 3.78 ppm for acarbose. The IC50 values of the extract were included in the medium category.

Anahtar Kelimeler

• Antidiabetic
• Desmanthus virgatus
• ethanol extract
• in silico
• in vitro

Kaynakça

1. 1. Oliveira, H., Fernandes, A., Brás, N.F., Mateus, N., de Freitas, V., Fernandes, I. (2020). Anthocyanins as antidiabetic agents in vitro and in silico approaches of preventive and therapeutic effects. Molecules. 25(17), 1-30. [CrossRef]
2. 2. Malik, A., Jamil, U., Butt, T.T., Waquar, S., Gan, S.H., Shafique, H., Jafar, T.H. (2019). In silico and in vitro studies of lupeol and iso-orientin as potential antidiabetic agents in a rat model. Drug Design, Development and Therapy. 13, 1501-1513. [CrossRef]
3. 3. Yaribeygi, H., Sathyapalan, T., Atkin, S.L., Sahebkar, A. (2020). Molecular mechanisms linking oxidative stress and diabetes mellitus. Oxidative Medicine and Cellular Longevity. 2020, 8609213. [CrossRef]
4. 4. Rachdaoui N. (2020). Insulin: The friend and the foe in the development of type 2 diabetes mellitus. International Journal of Molecular Sciences. 21(5), 1-21. [CrossRef]
5. 5. Mohajan, D, Mohajan, H.K. (2023). Hyperglycaemia among diabetes patients: A preventive approach. International Journal of Innovative Science and research Technology, 2(6), 27-33. [CrossRef]
6. 6. Elhady, S.S., Youssef, F.S., Alahdal, A.M., Almasri, D.M., Ashour, M.L. (2021). Anti-hyperglycaemic evaluation of Buddleia indica leaves using in vitro, in vivo and in silico studies and its correlation with the major phytoconstituents. Plants, 10(11). [CrossRef]
7. 7. Aktas, G., Kocak, M.Z., Bilgin, S., Atak, B.M., Duman, T.T., Kurtkulagi, O. (2021). Uric acid to HDL cholesterol ratio is a strong predictor of diabetic control in men with type 2 diabetes mellitus. Aging Male, 23(5),1098-1102. [CrossRef]
8. 8. Liu, J., Bai, R., Chai, Z., Cooper, M.E., Zimmet, P.Z., Zhang, L. (2022). Low-and middle-income countries demonstrate rapid growth of type 2 diabetes: An analysis based on global burden of disease 1990-2019 data. Diabetologia, 65(8), 253-260. [CrossRef]

9. 9. Khatimah, H. (2023). Analisis tingkat pengetahuan faktor risiko DM dengan status DM pada guru SMA negeri di kelurahan Paccerakang. Jurnal Nursing Update, 14, 86–92.
10. 10. Dirir, A.M., Daou, M., Yousef, A.F., Yousef, L.F. (2022). A review of alpha-glucosidase inhibitors from plants as potential candidates for the treatment of type-2 diabetes. In Phytochemistry Reviews. Springer Netherlands. 21(4). [CrossRef]
11. 11. Eizirik, D.L., Pasquali, L., Cnop, M. (2020). Pancreatic β-cells in type 1 and type 2 diabetes mellitus: Different pathways to failure. Nature Reviews Endocrinology, 16(7), 349-362. [CrossRef]
12. 12. Faida, A.N., Dyah, Y., Santik, P. (2020). Kejadian diabetes melitus tipe I pada usia 10-30 tahun. Higeia Journal of Public Health. 4(1), 33-42.
13. 13. Dafriani, P., Dewi, R.I.S. (2019). Tingkat pengetahuan pada pasien diabetes melitus (DM) tipe 2. Jurnal Abdimas Saintika, 1(1), 45-50.
14. 14. Ayuni, N.M.I. (2020). Efek buah naga merah (Hylocereus polyrhizus) terhadap penurunan kadar glukosa darah pada diabetes tipe 2 effect of red dragon fruit (Hylocereus polyrhizus) on reducing blood glucose levels in type 2 diabetes. Jurnal Ilmiah Kesehatan Sandi Husada, 11(1), 554-560. [CrossRef]
15. 15. Galicia-garcia, U., Benito-vicente, A., Jebari, S., Larrea-sebal, A. (2020). Costus ignus: Insulin plant and it’s preparations as remedial approach for diabetes mellitus. International Journal of Molecular Sciences, 21(6275), 1-34.
16. 16. Syachriyani, S., Firmansyah, F. (2022). Potensi antihiperglikemik ekstrak kulit buah semangka (Citrullus lanatus linn.) terhadap diabetes mellitus melalui penghambatan aktivitas enzim alfa glukosidase. Jurnal Mandala Pharmacon Indonesia, 8(2), 243-251. [CrossRef]
17. 17. Kalinovskii, A.P., Sintsova, O.V., Gladkikh, I.N., Leychenko, E.V. (2023). Natural inhibitors of mammalian α-amylases as promising drugs for the treatment of metabolic diseases. International Journal of Molecular Sciences, 24(22), 16514.
18. 18. Sameeh, M.Y., Khowdiary, M.M., Nassar, H.S., Abdelall, M.M., Amer, H.H., Hamed, A. (2022). Thiazolidinedione derivatives: in silico, in vitro, in vivo, antioxidant and anti-diabetic evaluation. Molecules, 27(830),1-15.
19. 19. Shivanagoudra, S.R., Perera, W.H., Perez, J.L., Athrey, G., Sun, Y., Wu, C.S. (2019). In vitro and in silico elucidation of antidiabetic and anti-inflammatory activities of bioactive compounds from Momordica charantia L. Bioorganic & Medicinal Chemistry, 27(14), 3097-3109. [CrossRef]
20. 20. Saputra, B.A. (2021). Potensi ekstrak daun sambiloto sebagai obat antidiabetes. Jurnal Penelitian Perawat Profesional, 3(2), 253-260. [CrossRef]
21. 21. Indrianingsih, A.W., Wulanjati, M.P., Windarsih, A., Bhattacharjya, D.K., Suzuki, T., Katayama, T. (2021). In vitro studies of antioxidant, antidiabetic, and antibacterial activities of Theobroma cacao, Anonna muricata and Clitoria ternatea. Biocatalysis and Agricultural Biotechnology, 33, 101995. [CrossRef]
22. 22. Mugaranja, K.P., Kulal, A. (2020). Alpha-glucosidase inhibition activity of phenolic fraction from Simarouba glauca: An in-vitro, in-silico and kinetic study. Heliyon. 6(7), e04392. [CrossRef]
23. 23. Adiputra, R. (2023). Efek samping penggunaan obat anti diabetes jangka panjang: Sebuah meta analisis. Jurnal Kesehatan Tambusai. 4(3).
24. 24. Khanal, P., Patil, B.M. (2020). Integration of in silico, in vitro and ex vivo pharmacology to decode the anti-diabetic action of Ficus benghalensis L. bark. Journal of Diabetes & Metabolic Disorders, 19, 1325-1337. [CrossRef]
25. 25. Sembiring, E.N., Elya, B., Sauriasari, R. (2018). Phytochemical screening, total flavonoid and total phenolic content and antioxidant activity of different parts of Caesalpinia bonduc (L.) Roxb. Pharmacognosy Journal., 10(1), 123-127.
26. 26. Hikmawanti, N.P.E., Fatmawati, S., Asri, A.W. (2021). The effect of ethanol concentrations as the extraction solvent on antioxidant activity of katuk (Sauropus androgynus (L.) Merr.) leaves extracts. IOP Conference Series: Earth and Environmental Science, 755(1). [CrossRef]
27. 27. Jitrangsri, K., Chaidedgumjorn, A., Satiraphan, M. (2020). Effect of ethanol percentage upon various extraction methods of peanut based on antioxidant activity with trans-resveratrol and total phenolic contents. Pharmaceutical Sciences Asia, 47(2), 164-172. [CrossRef]
28. 28. Etsassala, N.G.E.R, Badmus, J.A., Marnewick, J.L., Iwuoha, E.I., Nchu, F., Hussein, A.A. (2020). Alpha-glucosidase and alpha-amylase inhibitory activities, molecular docking, and antioxidant capacities of Salvia aurita constituents. Antioxidants, 9(11), 1-14. [CrossRef]
29. 29. Sadik, F., Rifqah, A.A.A. (2022). Standarisasi parameter spesifik ekstrak etanol daun pegagan (Centella asiatica L.) sebagai antidiabetes. Journal Syifa Science and Clinical Research, 4(1), 1-9. [CrossRef]
30. 30. Azzahra, A., Farhani, N., Syahfitri, W., Pasaribu, S.F. (2022). Potensi kandungan flavonoid dalam kayu bajakah sebagai antidiabetes. Jurnal Pendidik Tambusai, 6(2), 14345-14350.
31. 31. Ghorbani, A. (2017). Mechanisms of antidiabetic effects of flavonoid rutin. Biomedicine & Pharmacotherapy, 96, 305-312. [CrossRef]
32. 32. Ullah, A., Munir, S., Badshah, S.L., Khan, N., Ghani, L., Poulson, B.G. (2020). Important flavonoids and their role as a therapeutic agent. Molecules. 25(22), 1-39. [CrossRef]
33. 33. Shehadeh, M.B., Suaifan, G.A.R.Y., Abu-Odeh, A.M. (2021). Plants secondary metabolites as blood glucose-lowering molecules. Molecules, 26(14), 1-46. [CrossRef]
34. 34. Blahova, J., Martiniakova, M., Babikova, M., Kovacova, V., Mondockova, V., Omelka, R. (2021). Pharmaceutical drugs and natural therapeutic products for the treatment of type 2 diabetes mellitus. Pharmaceuticals, 14(8), 1-32. [CrossRef]
35. 35. Syifa, P., Bertha, R. (2023). Uji in silico aktivitas senyawa kumarin turunannya terhadap enzim alfa-glukosidase antidiabetes. Jurnal Riset Farmasi, 3(1), 9-16. [CrossRef]
36. 36. Chen, X., Li, H., Tian, L., Li, Q., Luo, J., Zhang, Y. (2020). Analysis of the physicochemical properties of acaricides based on Lipinski’s rule of five. Journal of Computational Biology, 27(9), 1397-1406. [CrossRef]
37. 37. Truzzi, F., Tibaldi, C., Zhang, Y., Dinelli, G., D′Amen, E. (2021). An overview on dietary polyphenols and their biopharmaceutical classification system (BCS). International Journal of Molecular Sciences, 22(5514), 1-23. [CrossRef]
38. 38. Mishra, M., Arukha, A.P., Patel, A.K., Behera, N., Mohanta, T.K., Yadav D. (2020). Multi-drug resistant coliform: Water sanitary standards and health hazards. Journal of King Saud University-Science, 32(9), 1-8. [CrossRef]
39. 39. Annisa, F.S., Hilda, A., Taufik, M.F. (2022). Uji aktivitas in silico senyawa amritoside, tinosporaside dan turunannya sebagai kanditat senyawa. Bandung Conference Series Pharmacy, 2(2), 1-10. [CrossRef]
40. 40. Sari, I.W., Junaidin, Pratiwi, D. (2020). Studi molecular docking senyawa flavonoid herba kumis kucing (Orthosiphon stamineus B.) pada reseptor α-glukosidase sebagai antidiabetes tipe 2. Journal Farmagazine, 7(2), 54-60. [CrossRef]
41. 41. Prasetiawati, R., Damayanti, A., Suwandi, D.W. (2023). Simulasi dinamika molekuler senyawa aktif akar pakis tangkur (Polypodium feei METT) sebagai inhibitor enzim inducible nitric oxide synthase (iNOS). Prosiding Seminar Nasional Diseminasi Penelitian, 3(1), 390-400.
42. 42. Laily, A.N., Khoiri, A.N. (2016). Identifikasi senyawa antidiabetes secara in silico pada Carica pubescens Lenne & K. Koch. El–Hayah. 5(4), 135-142. [CrossRef]
43. 43. Ali, M., Hassan, M., Ansari, S.A., Alkahtani, H.M., Al-Rasheed, L.S., Ansari, S.A. (2024). Quercetin and kaempferol as multi-targeting antidiabetic agents against mouse model of chemically induced type 2 diabetes. Pharmaceuticals, 17(6), 757. [CrossRef]
44. 44. Yu, R., Zhang, Y., Wang, T., Duan, J., Li, X. (2024). Effect of tricin on cardiomyocyte damage caused by diabetic cardiomyopathy (DCM). BMC Cardiovascular Disorders, 24(1), 1-8. [CrossRef]
45. 45. Niaz, A., Adnan, A., Bashir, R., Mumtaz, M.W., Raza, S.A., Rashid, U., Tan, C.P., Tan, T.B. (2021). The in vitro α-glucosidase inhibition activity of various solvent fractions of Tamarix dioica and 1H-NMR based metabolite identification and molecular docking analysis. Plants. 10(1128), 1-14.
46. 46. Arthur, D.E., Uzairu, A. (2019). Molecular docking studies on the interaction of NCI anticancer analogues with human phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit. Journal King Saud University-Science, 31(4), 1151-1166. [CrossRef]
47. 47. Alandijany, T.A., El-Daly, M.M., Tolah, A.M., Bajrai, L.H., Khateb, A.M., Alsaady, I.M. (2023). Investigating the mechanism of action of anti-dengue compounds as potential binders of Zika virus RNA-dependent RNA polymerase. Viruses, 15(7), 1-22. [CrossRef]
48. 48. Febrianda, L.H., Jawi, I.M., Widiarthini, I.A.A., Aman, I.G.M. (2024). Uji penghambatan aktivitas enzim alfa-glukosidase terhadap dua produk jamu kapsul ekstrak kayu manıs (Cinnamomum burmannii). Jurnal Medika Udayana, 13(02), 53-58.
49. 49. Poongunran, J., Perera, H.K.I., Jayasinghe, L., Fernando, I.T., Sivakanesan, R., Araya, H., Fujimoto, Y. (2017). Bioassay-guided fractionation and identification of α-amylase inhibitors from Syzygium cumini leaves. Pharmaceutical Biology, 55(1), 206-211. [CrossRef]
50. 50. Hilma, R., Gustina, N., Syahri, J. (2020). Pengukuran total fenolik, flavonoid, aktivitas antioksidan dan antidiabetes ekstrak etil asetat daun katemas (Euphorbia heterophylla L.) secara in vitro dan in silico melalui inhibisi enzim α-glukosidase. ALCHEMY Jurnal Penelitian Kimia,16(2), 240-249. [CrossRef]
51. 51. Mechchate, H., Es-Safi, I., Louba, A., Alqahtani, A.S., Nasr, F.A., Noman, O.M. (2021). In vitro alpha-amylase and alpha-glucosidase inhibitory activity and in vivo antidiabetic activity of Withania frutescens L. foliar extract. Molecules, 26(2), 1-10. [CrossRef]
52. 52. Sinulingga, S., Subandrate, S., Safyudin, S. (2020). Uji fitokimia dan potensi antidiabetes fraksi etanol air benalu kersen (Dendrophtoe petandra (L) Miq). Jurnal Kedokteran dan Kesehatan, 16(1), 76-83. [CrossRef]
53. 53. Abdelmonsef, M., Shawky, E., Ghareeb, D.A., El Naggar, E.M.B., El Newehy, N.M. (2024). Comprehensive metabolomics and chemometrics unravel potential anti-diabetic metabolites of pumpkin (Cucurbita pepo L.) fruits through UPLC-QqQ-MS and GC–MS analyses. Food Research International, 192(114771), 1-16. [CrossRef]
54. 54. Yuniarto, A., Selifiana, N. (2018). Aktivitas inhibisi enzim alfa-glukosidase dari ekstrak rimpang bangle (Zingiber cassumunar Roxb.) secara in vitro. Media Pharma Indonesia, 2(1), 22-25. [CrossRef]
55. 55. Fadhli, H., Hendri, S.N., Nurain, N.A. (2021). Aktivitas inhibisi enzim alfa-glukosidase dari ekstrak kulit batang bunga kupu-kupu (Bauhinia semibifida Roxb) secara in vitro. Jurnal Ilmiah Ibnu Sina: Ilmu Farmasi dan Kesehatan, 6(2), 223-231. [CrossRef]
56. 56. Zabidi, N.A., Ishak, N.A., Hamid, M., Ashari, S.E., Mohammad, L.M.A. (2021). Inhibitory evaluation of Curculigo latifolia on α-glucosidase, DPP (IV) and in vitro studies in antidiabetic with molecular docking relevance to type 2 diabetes mellitus. Journal of Enzyme Inhibition and Medicinal Chemistry, 36(1), 109-121. [CrossRef]
57. 57. Souhoka, F.A., Hattu, N., Huliselan, M. (2019). Uji aktivitas antioksidan ekstrak metanol biji kesumba keling (Bixa orellana L). Indonesian Journal of Chemical Research, 7(1), 25-31. [CrossRef]
58. 58. Kashtoh, H., Baek, K.H. (2022). Recent updates on phytoconstituent alpha-glucosidase inhibitors: An approach towards the treatment of type two diabetes. Plants, 11(20), 1-25. [CrossRef]
59. 59. Seboletswe, P., Kumar, G., Kubone, L., Olofinsan, K., Idris, A., Islam, M.S., Singh, P. (2024). Ultrasound-assisted synthesis of 4-thiazolidinone Schiff bases and their antioxidant, α-glucosidase, α-amylase inhibition, mode of inhibition and computational studies. Medicinal Chemistry Research. [CrossRef]