Araştırma Makalesi
BibTex RIS Kaynak Göster

Şeker hastalığı üzerinde quercetin, gallik asit, oleanolik asit ve ursolik asitin in siliko analizi

Yıl 2022, Cilt: 3 Sayı: 3, 100 - 110, 30.09.2022

Merve Aras Özlem Yayıntaş

https://doi.org/10.55665/troiamedj.1163784

Öz

Amaç: Diyabet, pankreatik β hücrelerinin yeterli seviyede insülin üretememesin ya da üretilen insülinin vücut tarafından etkili şekilde kullanılamaması sonucu ortaya çıkan bir hastalıktır. IDF diyabet atlasının verilerine göre 2021’de dünya çapında 20-79 yaş aralığında 537 milyon diyabetli hasta olduğu ve bu sayının 2030’da 643 milyon, 2045’te ise 783 milyon olmasının beklendiği bildirilmiştir. Bu derece ciddi düzeyde olan diyabet hastalığını kontrol altına alabilmek için bilim insanları çeşitli tedavi yöntemleri bulmaya çalışmaktadır. Bunlardan biri de doğal tedavilerdir. Bu çalışmada, antidiyabetik özelliklere sahip quercetin, gallik asit, oleanolik asit ve ursolik asidin diyabetle ilişkili renin, katepsin-d, T-PA, leptin, MASP-2, FABP4 proteinlerine afinite değerleri araştırıldı. Yöntem: Moleküler docking analizi için öncelikle UCSF Chimera 1.15 yazılımı ile proteinlerden istenmeyen kalıntılar ve zincirler silinmiş ve polar hidrojen atomları eklenerek docking için hazırlanmıştır. Daha sonra ligand olarak kullanılan kuersetin, gallik asit, oleanolik asit ve ursolik asit minimum enerji konformasyonuna getirilmiştir. Moleküler yerleştirme için hazırlanan protein ve ligand, Autodock Tools 1.5.6 yazılımı ile analiz edildi. Moleküler yerleştirme sonuçları, BIOVIA Discovery Studio ve protein plus yazılımı ile görüntülendi. Ayrıca ADME analizi için pkCSM yazılımı kullanılmıştır. Sonuç: Sonuç olarak, quercetin diğer üç flavonoidden daha etkili bulunmuştur.

Anahtar Kelimeler

flavonoidler şeker hastalığı ADME moleküler yerleştirme

Kaynakça

  • 1. Tanrıverdi MH, Çelepkolu T, Aslanhan H. Diabetes mellitus and primary healthcare. J Clin Exp Investig. 2015;4(4):562–7.
  • 2. Chawla T, Sharma D, Singh A. Role of the renin angio-tensin system in diabetic nephropathy. 2010;1(5):141–5.
  • 3. Öztürk S, Karadağ S, Bozkurt OB, et al. Geriatrik ve nongeriatrik popülasyonda aşikar diyabetik nefropati pro-gresyonu üzerine renin-anjiotensin-aldosteron blokajının etkisi. Journal of Geriatrics and Geriatric Neuropsychiatry. 2011;2(2-3):9-14
  • 4. Katsiki N, Mikhailidis DP, Banach M. Leptin, cardiovas-cular diseases and type 2 diabetes mellitus review-article. Acta Pharmacol Sin. 2018;39(7):1176–88.
  • 5. Li L, Mamputu JC, Wiernsperger N, Renier G. Signaling pathways involved in human vascular smooth muscle cell proliferation and matrix metalloproteinase-2 expression induced by leptin: Inhibitory effect of metformin. Diabetes. 2005;54(7):2227–34.
  • 6. Furuhashi M, Hiramitsu S, Mita T, et al. Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus. J Lipid Res. 2015;56(12):2372–80.
  • 7. Jenny L, Ajjan R, King R, Thiel S, Schroeder V. Plasma levels of mannan-binding lectin-associated serine proteases MASP-1 and MASP-2 are elevated in type 1 diabetes and correlate with glycaemic control. Clin Exp Immunol. 2015;180(2):227–32.
  • 8. Eliasson MCE, Jansson JH, Lindahl B, Stegmayr B. High levels of tissue plasminogen activator (tPA) antigen precede the development of type 2 diabetes in a longitudinal popula-tion study. The Northern Sweden MONICA Study. Cardio-vasc Diabetol. 2003;2(Cvd):1–7.
  • 9. Yüksek V, Dede S, Çetin S, et al. The effect of thyme (thymus vulgaris l.) and blackhead thyme (thymbra spicata l.) administered on serum protein fractions in experimental diabetic rats. Van Med J. 2021;28(2):193–8.
  • 10. Krzaczkowski L, Wright M, Rebérioux D, Massiot G, Etiévant C, Gairin JE. Pharmacological screening of bryo-phyte extracts that inhibit growth and induce abnormal phenotypes in human HeLa cancer cells. Fundam Clin Pharmacol. 2009;23(4):473–82.
  • 11. Eitah HE, Maklad YA, Abdelkader NF, Gamal el Din AA, Badawi MA, Kenawy SA. Modulating impacts of quercetin/sitagliptin combination on streptozotocin-induced diabetes mellitus in rats. Toxicol Appl Pharmacol. 2019;365:30–40.
  • 12. Rifaai RA, El-Tahawy NF, Ali Saber E. Effect of quer-cetin on the endocrine pancreas of the experimentally induced diabetes in male albino rats: a histological and im-munohistochemical study. J Diabetes Metab. 2012;03(03).
  • 13. Adewole SO, Caxton-Martins EA. Quercetin and exercise treatment on the morphology of pancreatic β-cells of streptozotocin-treated diabetic rats. Journal of Mining and Geology 2006;5(1-2):52-72.
  • 14. Parichatikanond W, Pinthong D, Mangmool S. Blockade of the renin-angiotensin system with delphinidin, cyanin, and quercetin. Planta Med. 2012;78(15):1626–32.
  • 15. Tan Y, Tam CC, Rolston M, Alves P, Chen L, Meng S, et al. Quercetin ameliorates insulin resistance and restores gut microbiome in mice on high-fat diets. Antioxidants. 2021;10(8):1–17.
  • 16. Sohn KH, Lee HY, Chung HY, Young HS, Yi SY, Kim KW. Anti-angiogenic activity of triterpene acids. Cancer Lett. 1995;94(2):213–8.
  • 17. Do Nascimento PGG, Lemos TLG, Bizerra AMC, et al. Antibacterial and antioxidant activities of ursolic acid and derivatives. Molecules. 2014;19(1):1317–27.
  • 18. Ovesná Z. Pentacyclic triterpenoic acids: new chemo-protective compounds. Minireview. Neoplasma. 2004;51(5): 327-33.
  • 19. Banno N, Akihisa T, Tokuda H, et al. Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects. Biosci Bio-technol Biochem. 2004;68(1):85–90.
  • 20. Raphael TJ, Kuttan G. Effect of naturally occurring triterpenoids glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin on the immune system. Phytomedicine. 2003;10(6–7):483–9.
  • 21. Zhang W, Hong D, Zhou Y, et al. Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B, enhancing insulin receptor phosphorylation and stimulating glucose uptake. Biochim Biophys Acta Gen Subj. 2006;1760(10):1505–12.
  • 22. Ma TK, Xu L, Lu LX, et al. Ursolic acid treatment alle-viates diabetic kidney injury by regulating the ARAP1/AT1R signaling pathway. Diabetes, Metab Syndr Obes Targets Ther. 2019; 12:2597–608.
  • 23. Jia Y, Kim S, Kim J, et al. Ursolic acid improves lipid and glucose metabolism in high-fat-fed C57BL/6J mice by activating peroxisome proliferator-activated receptor alpha and hepatic autophagy. Mol Nutr Food Res. 2015;59(2):344–54.
  • 24. He Y, Li Y, Zhao T, Wang Y, Sun C. Ursolic Acid Inhibits Adipogenesis in 3T3-L1 Adipocytes through LKB1/AMPK Pathway. PLoS One. 2013;8(7).
  • 25. Lin Z, Zhang Y, Zhang Y, et al. Oleanolic acid derivative NPLC441 potently stimulates glucose transport in 3T3-L1 adipocytes via a multi-target mechanism. Biochem Pharmacol. 2008;76(10):1251–62.
  • 26. Lee ES, Kim HM, Kang JS, et al. Oleanolic acid and N-acetylcysteine ameliorate diabetic nephropathy through reduction of oxidative stress and endoplasmic reticulum stress in a type 2 diabetic rat model. Nephrol Dial Transplant. 2016;31(3):391–400.
  • 27. Ahn YM, Choi YH, Yoon JJ, et al. Oleanolic acid modu-lates the renin-angiotensin system and cardiac natriuretic hormone concomitantly with volume and pressure balance in rats. Eur J Pharmacol. 2017;809:231–41.
  • 28. dos Santos JFS, Tintino SR, de Freitas TS, et al. In vitro e in silico evaluation of the inhibition of Staphylococcus aureus efflux pumps by caffeic and gallic acid. Comp Immunol Microbiol Infect Dis. 2018;57:22–8.
  • 29. Lim KS, Park JK, Jeong MH, et al. Anti-inflammatory effect of gallic acid-eluting stent in a porcine coronary restenosis model. Acta Cardiol Sin. 2018;34(3):224–32.
  • 30. Mudnic I, Modun D, Rastija V, et al. Antioxidative and vasodilatory effects of phenolic acids in wine. Food Chem. 2010;119(3):1205–10.
  • 31. Verma S, Singh A, Mishra A. Gallic acid: Molecular rival of cancer. Environ Toxicol Pharmacol. 2013;35(3):473–85.
  • 32. Huang DW, Chang WC, Wu JSB, Shih RW, Shen SC. Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet. Nutr Res. 2016;36(2):150–60.
  • 33. Garud MS, Kulkarni YA. Gallic acid attenuates type I diabetic nephropathy in rats. Chem Biol Interact. 2018;282:69–76.
  • 34. Hsu CL, Yen GC. Effect of gallic acid on high fat diet-induced dyslipidaemia, hepatosteatosis and oxidative stress in rats. Br J Nutr. 2007;98(4):727–35.
  • 35. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, effi-cient optimization, and multithreading. Journal of computa-tional chemistry, 2010;31(2):455–461.
  • 36. Ferreira LLG, Andricopulo AD. ADMET modelling approaches in drug discovery. Drug Discov Today. 2019;24(5):1157–65.
  • 37. Özkan HN. Alkillenmiş tetrazol türevi bileşiklerin ab-sorpsiyon, dağılım, metabolizma ve atılım (ADME) özel-liklerinin araştırılması. Süleyman Demirel Üniversitesi Fen Edeb Fakültesi Fen Derg. 2019;14(2):384–94.
  • 38. IDF Diabetes Atlas, Tenth Edition (2022). Available at: https://diabetesatlas.org/ (Accessed: 17 May 2022). 39. Yüksel N. Sitokrom P450 enzim sistemi ve ilaç etkileşmeleri. 35 Ulus Psikiyatr Kongresi. 2001; Ek 1:5-16.
  • 40. Yi H, Peng H, Wu X, et al. The therapeutic effects and mechanisms of quercetin on metabolic diseases: pharmaco-logical data and clinical evidence. Hindawi Oxidative Medi-cine and Cellular Longevity Volume 2021, Article ID 6678662. DOI: 10.1155/2021/6678662.

In silico analysis of quercetin, gallic acid, oleanolic acid, and ursolic acid on diabetes mellitus

Yıl 2022, Cilt: 3 Sayı: 3, 100 - 110, 30.09.2022

Merve Aras Özlem Yayıntaş

https://doi.org/10.55665/troiamedj.1163784

Öz

Objective: Diabetes is a disease that occurs due to pancreatic β cells failing to produce enough insulin or the inability to use the produced insulin effectively in the body. According to the data of the IDF diabetes atlas, it has been reported that there are 537 million diabetic patients aged 20-79 worldwide in 2021 and this number is expected to reach 643 million in 2030 and 783 million in 2045. To control diabetes at such a severe level, scientists are trying to find various treatment methods. One of them is natural treatments. In this study, the affinity values of quercetin, gallic acid, oleanolic acid and ursolic acid, which have antidiabetic properties, to diabetes-related renin, cathepsin-d, T-PA, leptin, MASP-2, FABP4 proteins were investigated. Methods: For molecular docking analysis, unwanted residues and chains were deleted from the proteins with UCSF Chimera 1.15 software and prepared for docking by adding polar hydrogen atoms. Next, quercetin, gallic acid, oleanolic acid and ursolic acid used as ligands were brought to minimum energy conformation. Protein and ligands prepared for molecular docking were analyzed with Autodock Tools 1.5.6 software. Molecular docking results were viewed with BIOVIA Discovery Studio and protein plus software. Moreover, pkCSM software was used for ADME analysis. Conclusion: As a result, quercetin was found to be more effective than the other three flavonoids.

Anahtar Kelimeler

flavonoids diabetes mellitus ADME molecular docking

Kaynakça

  • 1. Tanrıverdi MH, Çelepkolu T, Aslanhan H. Diabetes mellitus and primary healthcare. J Clin Exp Investig. 2015;4(4):562–7.
  • 2. Chawla T, Sharma D, Singh A. Role of the renin angio-tensin system in diabetic nephropathy. 2010;1(5):141–5.
  • 3. Öztürk S, Karadağ S, Bozkurt OB, et al. Geriatrik ve nongeriatrik popülasyonda aşikar diyabetik nefropati pro-gresyonu üzerine renin-anjiotensin-aldosteron blokajının etkisi. Journal of Geriatrics and Geriatric Neuropsychiatry. 2011;2(2-3):9-14
  • 4. Katsiki N, Mikhailidis DP, Banach M. Leptin, cardiovas-cular diseases and type 2 diabetes mellitus review-article. Acta Pharmacol Sin. 2018;39(7):1176–88.
  • 5. Li L, Mamputu JC, Wiernsperger N, Renier G. Signaling pathways involved in human vascular smooth muscle cell proliferation and matrix metalloproteinase-2 expression induced by leptin: Inhibitory effect of metformin. Diabetes. 2005;54(7):2227–34.
  • 6. Furuhashi M, Hiramitsu S, Mita T, et al. Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus. J Lipid Res. 2015;56(12):2372–80.
  • 7. Jenny L, Ajjan R, King R, Thiel S, Schroeder V. Plasma levels of mannan-binding lectin-associated serine proteases MASP-1 and MASP-2 are elevated in type 1 diabetes and correlate with glycaemic control. Clin Exp Immunol. 2015;180(2):227–32.
  • 8. Eliasson MCE, Jansson JH, Lindahl B, Stegmayr B. High levels of tissue plasminogen activator (tPA) antigen precede the development of type 2 diabetes in a longitudinal popula-tion study. The Northern Sweden MONICA Study. Cardio-vasc Diabetol. 2003;2(Cvd):1–7.
  • 9. Yüksek V, Dede S, Çetin S, et al. The effect of thyme (thymus vulgaris l.) and blackhead thyme (thymbra spicata l.) administered on serum protein fractions in experimental diabetic rats. Van Med J. 2021;28(2):193–8.
  • 10. Krzaczkowski L, Wright M, Rebérioux D, Massiot G, Etiévant C, Gairin JE. Pharmacological screening of bryo-phyte extracts that inhibit growth and induce abnormal phenotypes in human HeLa cancer cells. Fundam Clin Pharmacol. 2009;23(4):473–82.
  • 11. Eitah HE, Maklad YA, Abdelkader NF, Gamal el Din AA, Badawi MA, Kenawy SA. Modulating impacts of quercetin/sitagliptin combination on streptozotocin-induced diabetes mellitus in rats. Toxicol Appl Pharmacol. 2019;365:30–40.
  • 12. Rifaai RA, El-Tahawy NF, Ali Saber E. Effect of quer-cetin on the endocrine pancreas of the experimentally induced diabetes in male albino rats: a histological and im-munohistochemical study. J Diabetes Metab. 2012;03(03).
  • 13. Adewole SO, Caxton-Martins EA. Quercetin and exercise treatment on the morphology of pancreatic β-cells of streptozotocin-treated diabetic rats. Journal of Mining and Geology 2006;5(1-2):52-72.
  • 14. Parichatikanond W, Pinthong D, Mangmool S. Blockade of the renin-angiotensin system with delphinidin, cyanin, and quercetin. Planta Med. 2012;78(15):1626–32.
  • 15. Tan Y, Tam CC, Rolston M, Alves P, Chen L, Meng S, et al. Quercetin ameliorates insulin resistance and restores gut microbiome in mice on high-fat diets. Antioxidants. 2021;10(8):1–17.
  • 16. Sohn KH, Lee HY, Chung HY, Young HS, Yi SY, Kim KW. Anti-angiogenic activity of triterpene acids. Cancer Lett. 1995;94(2):213–8.
  • 17. Do Nascimento PGG, Lemos TLG, Bizerra AMC, et al. Antibacterial and antioxidant activities of ursolic acid and derivatives. Molecules. 2014;19(1):1317–27.
  • 18. Ovesná Z. Pentacyclic triterpenoic acids: new chemo-protective compounds. Minireview. Neoplasma. 2004;51(5): 327-33.
  • 19. Banno N, Akihisa T, Tokuda H, et al. Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects. Biosci Bio-technol Biochem. 2004;68(1):85–90.
  • 20. Raphael TJ, Kuttan G. Effect of naturally occurring triterpenoids glycyrrhizic acid, ursolic acid, oleanolic acid and nomilin on the immune system. Phytomedicine. 2003;10(6–7):483–9.
  • 21. Zhang W, Hong D, Zhou Y, et al. Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B, enhancing insulin receptor phosphorylation and stimulating glucose uptake. Biochim Biophys Acta Gen Subj. 2006;1760(10):1505–12.
  • 22. Ma TK, Xu L, Lu LX, et al. Ursolic acid treatment alle-viates diabetic kidney injury by regulating the ARAP1/AT1R signaling pathway. Diabetes, Metab Syndr Obes Targets Ther. 2019; 12:2597–608.
  • 23. Jia Y, Kim S, Kim J, et al. Ursolic acid improves lipid and glucose metabolism in high-fat-fed C57BL/6J mice by activating peroxisome proliferator-activated receptor alpha and hepatic autophagy. Mol Nutr Food Res. 2015;59(2):344–54.
  • 24. He Y, Li Y, Zhao T, Wang Y, Sun C. Ursolic Acid Inhibits Adipogenesis in 3T3-L1 Adipocytes through LKB1/AMPK Pathway. PLoS One. 2013;8(7).
  • 25. Lin Z, Zhang Y, Zhang Y, et al. Oleanolic acid derivative NPLC441 potently stimulates glucose transport in 3T3-L1 adipocytes via a multi-target mechanism. Biochem Pharmacol. 2008;76(10):1251–62.
  • 26. Lee ES, Kim HM, Kang JS, et al. Oleanolic acid and N-acetylcysteine ameliorate diabetic nephropathy through reduction of oxidative stress and endoplasmic reticulum stress in a type 2 diabetic rat model. Nephrol Dial Transplant. 2016;31(3):391–400.
  • 27. Ahn YM, Choi YH, Yoon JJ, et al. Oleanolic acid modu-lates the renin-angiotensin system and cardiac natriuretic hormone concomitantly with volume and pressure balance in rats. Eur J Pharmacol. 2017;809:231–41.
  • 28. dos Santos JFS, Tintino SR, de Freitas TS, et al. In vitro e in silico evaluation of the inhibition of Staphylococcus aureus efflux pumps by caffeic and gallic acid. Comp Immunol Microbiol Infect Dis. 2018;57:22–8.
  • 29. Lim KS, Park JK, Jeong MH, et al. Anti-inflammatory effect of gallic acid-eluting stent in a porcine coronary restenosis model. Acta Cardiol Sin. 2018;34(3):224–32.
  • 30. Mudnic I, Modun D, Rastija V, et al. Antioxidative and vasodilatory effects of phenolic acids in wine. Food Chem. 2010;119(3):1205–10.
  • 31. Verma S, Singh A, Mishra A. Gallic acid: Molecular rival of cancer. Environ Toxicol Pharmacol. 2013;35(3):473–85.
  • 32. Huang DW, Chang WC, Wu JSB, Shih RW, Shen SC. Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet. Nutr Res. 2016;36(2):150–60.
  • 33. Garud MS, Kulkarni YA. Gallic acid attenuates type I diabetic nephropathy in rats. Chem Biol Interact. 2018;282:69–76.
  • 34. Hsu CL, Yen GC. Effect of gallic acid on high fat diet-induced dyslipidaemia, hepatosteatosis and oxidative stress in rats. Br J Nutr. 2007;98(4):727–35.
  • 35. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, effi-cient optimization, and multithreading. Journal of computa-tional chemistry, 2010;31(2):455–461.
  • 36. Ferreira LLG, Andricopulo AD. ADMET modelling approaches in drug discovery. Drug Discov Today. 2019;24(5):1157–65.
  • 37. Özkan HN. Alkillenmiş tetrazol türevi bileşiklerin ab-sorpsiyon, dağılım, metabolizma ve atılım (ADME) özel-liklerinin araştırılması. Süleyman Demirel Üniversitesi Fen Edeb Fakültesi Fen Derg. 2019;14(2):384–94.
  • 38. IDF Diabetes Atlas, Tenth Edition (2022). Available at: https://diabetesatlas.org/ (Accessed: 17 May 2022). 39. Yüksel N. Sitokrom P450 enzim sistemi ve ilaç etkileşmeleri. 35 Ulus Psikiyatr Kongresi. 2001; Ek 1:5-16.
  • 40. Yi H, Peng H, Wu X, et al. The therapeutic effects and mechanisms of quercetin on metabolic diseases: pharmaco-logical data and clinical evidence. Hindawi Oxidative Medi-cine and Cellular Longevity Volume 2021, Article ID 6678662. DOI: 10.1155/2021/6678662.
Toplam 39 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Makaleler
Yazarlar

Merve Aras 0000-0001-7047-2597

Özlem Yayıntaş 0000-0002-3554-1881

Yayımlanma Tarihi 30 Eylül 2022
Gönderilme Tarihi 18 Ağustos 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 3 Sayı: 3

Kaynak Göster

APA Aras, M., & Yayıntaş, Ö. (2022). In silico analysis of quercetin, gallic acid, oleanolic acid, and ursolic acid on diabetes mellitus. Troia Medical Journal, 3(3), 100-110. https://doi.org/10.55665/troiamedj.1163784
AMA Aras M, Yayıntaş Ö. In silico analysis of quercetin, gallic acid, oleanolic acid, and ursolic acid on diabetes mellitus. Troia Med J. Eylül 2022;3(3):100-110. doi:10.55665/troiamedj.1163784
Chicago Aras, Merve, ve Özlem Yayıntaş. “In Silico Analysis of Quercetin, Gallic Acid, Oleanolic Acid, and Ursolic Acid on Diabetes Mellitus”. Troia Medical Journal 3, sy. 3 (Eylül 2022): 100-110. https://doi.org/10.55665/troiamedj.1163784.
EndNote Aras M, Yayıntaş Ö (01 Eylül 2022) In silico analysis of quercetin, gallic acid, oleanolic acid, and ursolic acid on diabetes mellitus. Troia Medical Journal 3 3 100–110.
IEEE M. Aras ve Ö. Yayıntaş, “In silico analysis of quercetin, gallic acid, oleanolic acid, and ursolic acid on diabetes mellitus”, Troia Med J, c. 3, sy. 3, ss. 100–110, 2022, doi: 10.55665/troiamedj.1163784.
ISNAD Aras, Merve - Yayıntaş, Özlem. “In Silico Analysis of Quercetin, Gallic Acid, Oleanolic Acid, and Ursolic Acid on Diabetes Mellitus”. Troia Medical Journal 3/3 (Eylül 2022), 100-110. https://doi.org/10.55665/troiamedj.1163784.
JAMA Aras M, Yayıntaş Ö. In silico analysis of quercetin, gallic acid, oleanolic acid, and ursolic acid on diabetes mellitus. Troia Med J. 2022;3:100–110.
MLA Aras, Merve ve Özlem Yayıntaş. “In Silico Analysis of Quercetin, Gallic Acid, Oleanolic Acid, and Ursolic Acid on Diabetes Mellitus”. Troia Medical Journal, c. 3, sy. 3, 2022, ss. 100-1, doi:10.55665/troiamedj.1163784.
Vancouver Aras M, Yayıntaş Ö. In silico analysis of quercetin, gallic acid, oleanolic acid, and ursolic acid on diabetes mellitus. Troia Med J. 2022;3(3):100-1.
 Kapak Resmi İndir

Creative Commons Lisansı

Bu eser Creative Commons Alıntı-Türetilemez 4.0 Uluslararası Lisansı ile lisanslanmıştır.