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Bazı Flavonoidlerin Leptin ve Resisitin Proteinleri ile Etkileşimlerinin Moleküler Kenetlenme (Docking) Yöntemiyle İncelenmesi

Year 2024, Volume: 10 Issue: 2, 335 - 348, 31.08.2024

Abstract

Amaç: Obezite dünyada prevalansı hızla artan ve sağlığı tehdit eden önemli bir kronik hastalıktır. Flavonoidler açısından zengin bazı doğal gıdalar obezitenin önlenmesinde önemli bileşiklerdir. Bu çalışmada luteolin, tangeretin ve kaempferol gibi bazı flavonoidler ile obezite belirteçleri (leptin ve resistin) arasındaki etkileşimin araştırılması amaçlanmıştır.
Gereç ve Yöntemler: Luteolin, tangeretin ve kaempferol bağlanma afinitelerini hesaplamak için Autodock Vina programı kullanıldı. Leptin (PDB kodu: 1AX8) ve Resisitin (PDB kodu: 1RFX) proteinlerinin yapısı RCSB Protein Veri Bankasından alındı. Görselleştirme işlemleri BIOVA Discovery Studio Visualizer programı kullanılarak gerçekleştirildi.
Bulgular: Bu çalışmada, luteolin, tangeretin ve kaempferolün leptin ve resistin ile düşük bağlanma enerjisiyle etkileşime girdiği tespit edildi. Leptin proteini ile luteolin, tangeretin ve kaempferolün sırayla -6,3, -5,9 ve -6.1 kcal/mol bağlanma enerjileri ile etkileşim kurduğu tespit edildi. Resistin proteini ile ise -6,4, -6,5 ve -6,5 kcal/mol bağlanma enerjileri ile etkileşim kurduğu belirlendi.
Sonuç: Bu çalışmada, obezite proteinleri ile etkileşime giren bileşikler, bağlanma afinitesi ve etkileşim tipi açısından çeşitli sonuçlar göstermiştir. Luteolin, tangeretin ve kaempferolün leptin ve resistin ile düşük bağlanma enerjisiyle etkileşime girmesi, bu bileşiklerin obezite proteinlerinin bir inhibitörü olma potansiyelini göstermektedir.

References

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  • 2. Sarma S, Sockalingam S, Dash S. Obesity as a multisystem disease: Trends in obesity rates and obesity‐related complications. Diabetes, Obesity and Metabolism. 2021: 23: 3-16
  • 3. Keskin A, Recai A, Duran U, Sugeçti S. Physiological and Anti-obesity Effects of Melatonin and Niacin Supplements in Rat Models. Caucasian Journal of Science. 2021; 8(1): 27-37.
  • 4. Tutor AW, Lavie CJ, Kachur S, Milani RV, Ventura HO. Updates on obesity and the obesity paradox in cardiovascular diseases. Progress in Cardiovascular Diseases. 2023; 78: 2-10.
  • 5. Keleş V, Büyükgüzel K, Büyükgüzel E. Leptin ve Metabolik Düzenlenmedeki Rolü. Türkiye Diyabet ve Obezite Dergisi. 2018; 2(1): 17-2
  • 6. Picó C, Palou M, Pomar CA, Rodríguez AM, Palou A. Leptin as a key regulator of the adipose organ. Reviews in Endocrine and Metabolic Disorders. 2022; 23(1): 13-30.
  • 7. Münzberg H, Singh P, Heymsfield SB, Yu S, Morrison CD. Recent advances in understanding the role of leptin in energy homeostasis. F1000Research. 2020; 9.
  • 8. Boucsein A, Kamstra K, Tups A. Central signalling cross‐talk between insulin and leptin in glucose and energy homeostasis. Journal of Neuroendocrinology. 2021; 33(4): e12944.
  • 9. Simonds S, Pryor J, Cowley M. Leptin is a key regulator of glucose homeostasis in obesity. Physiology. 2023; 38(S1), 5793859.
  • 10. Tripathi D, Kant S, Pandey S, Ehtesham NZ. Resistin in metabolism, inflammation, and disease. The FEBS journal. 2020; 287(15): 3141-3149.
  • 11. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR. et al. The hormone resistin links obesity to diabetes. Nature. 2001; 409(6818): 307-312.
  • 12. Filková M, Haluzík M, Gay S, Šenolt L. The role of resistin as a regulator of inflammation: Implications for various human pathologies. Clinical immunology. 2009; 133(2): 157-170.
  • 13. Jamaluddin MS, Weakley SM, Yao Q, Chen C. Resistin: functional roles and therapeutic considerations for cardiovascular disease. British journal of pharmacology. 2012; 165(3): 622-632.
  • 14. Liu J, Cao J, Li Y, Guo F. Beneficial flavonoid in foods and anti-obesity effect. Food Reviews International. 2023; 39(1), 560-600.
  • 15. Al-Ishaq RK, Abotaleb M, Kubatka P, Kajo K, Büsselberg D. Flavonoids and their anti-diabetic effects: Cellular mechanisms and effects to improve blood sugar levels. Biomolecules. 2019; 9(9): 430.
  • 16. Alvesalo J, Vuorela H, Tammela P, Leinonen M, Saikku P, Vuorela P. Inhibitory effect of dietary phenolic compounds on Chlamydia pneumoniae in cell cultures. Biochemical pharmacology. 2006; 71(6): 735-741.
  • 17. Li C, Schluesener H. Health-promoting effects of the citrus flavanone hesperidin. Critical reviews in food science and nutrition. 2017; 57(3): 613-631.
  • 18. Kawser Hossain M, Abdal Dayem A, Han J, Yin Y, Kim K, Kumar Saha S, et al. Molecular mechanisms of the anti-obesity and anti-diabetic properties of flavonoids. International journal of molecular sciences. 2016; 17(4): 569.
  • 19. Oliveira AKDS, de Oliveira e Silva AM, Pereira RO, Santos AS, Barbosa Junior EV, Bezerra MT. et al. Anti-obesity properties and mechanism of action of flavonoids: A review. Critical Reviews in Food Science and Nutrition. 2022; 62(28): 7827-7848.
  • 20. Song D, Cheng L, Zhang X, Wu Z, Zheng X. The modulatory effect and the mechanism of flavonoids on obesity. Journal of food biochemistry. 2019; 43(8): e12954.
  • 21. Joshi H, Vastrad B, Joshi N, Vastrad C, Tengli A, Kotturshetti I. Identification of key pathways and genes in obesity using bioinformatics analysis and molecular docking studies. Frontiers in Endocrinology. 2021; 12: 628907.
  • 22. Panghiyangani R, Utami JP, Baitullah MA, Maulida ND. Molecular Docking of Citrus amblycarpa Active Compounds against FTO, Leptin, and Resistin Protein. Molecular and Cellular Biomedical Sciences. 2023; 7(1): 38-46.
  • 23. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry. 2010; 31(2): 455-461.
  • 24. Zhang F, Basinski MB, Beals JM, Briggs SL, Churgay LM, Clawson DK, et al. Crystal structure of the obese protein Ieptin-E100. Nature. 1997; 387(6629): 206-209.
  • 25. Patel SD, Rajala MW, Rossetti L, Scherer PE, Shapiro L. Disulfide-dependent multimeric assembly of resistin family hormones. Science. 2004; 304(5674): 1154-1158.
  • 26. Biovia DS, Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Richmond TJ. Dassault systèmes BIOVIA, discovery studio visualizer, v. 17.2, San Diego: Dassault Systèmes, 2016. J Chem Phys. 2000; 10: 21-9991.
  • 27. Strømgaard K, Krogsgaard-Larsen P, Madsen U. Textbook of Drug Design and Discovery. 5th ed. Boca Raton: CRC Press; 2017.
  • 28. Sousa JN, Queiroz LDRP, de Paula AMB, Guimarães ALS, Lescano CH, Aguilar CM, et al. Gallic acid as a Sestrin (SESN2) activator and potential obesity therapeutic agent: A molecular docking study. Gene. 2023; 883: 147683.
  • 29. Rufino AT, Costa VM, Carvalho F, Fernandes E. Flavonoids as antiobesity agents: A review. Medicinal Research Reviews. 2021; 41(1): 556-585.
  • 30. García-Barrado MJ, Iglesias-Osma MC, Pérez-García E, Carrero S, Blanco EJ, Carretero-Hernández M, Carretero J. Role of flavonoids in the interactions among obesity, inflammation, and autophagy. Pharmaceuticals. 2020; 13(11): 342.
  • 31. Liu Y, Fu X, Lan N, Li S, Zhang J, Wang S, et al. Luteolin protects against high fat diet-induced cognitive deficits in obesity mice. Behavioural brain research. 2014; 267: 178-188.
  • 32. Kwon EY, Jung UJ, Park T, Yun JW, Choi MS. Luteolin attenuates hepatic steatosis and insulin resistance through the interplay between the liver and adipose tissue in mice with diet-induced obesity. Diabetes. 2015; 64(5): 1658-1669.
  • 33. Sundaram R, Shanthi P, Sachdanandam P. Effect of tangeretin, a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats. Phytomedicine. 2014; 21(6): 793-799.
  • 34. Zang Y, Zhang L, Igarashi K, Yu C. The anti-obesity and anti-diabetic effects of kaempferol glycosides from unripe soybean leaves in high-fat-diet mice. Food & function. 2015; 6(3): 834-841.
  • 35. Luo C, Yang H, Tang C, Yao G, Kong L, He H, Zhou Y. Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats. International Immunopharmacology. 2015; 28(1): 744-750.
Year 2024, Volume: 10 Issue: 2, 335 - 348, 31.08.2024

Abstract

References

  • 1. Sugeçti S. Role of protein oxidation, lipid peroxidation and antioxidant defense systems on diabetes mellitus. Aurum Journal of Health Sciences. 2018; 1(1): 47-54.
  • 2. Sarma S, Sockalingam S, Dash S. Obesity as a multisystem disease: Trends in obesity rates and obesity‐related complications. Diabetes, Obesity and Metabolism. 2021: 23: 3-16
  • 3. Keskin A, Recai A, Duran U, Sugeçti S. Physiological and Anti-obesity Effects of Melatonin and Niacin Supplements in Rat Models. Caucasian Journal of Science. 2021; 8(1): 27-37.
  • 4. Tutor AW, Lavie CJ, Kachur S, Milani RV, Ventura HO. Updates on obesity and the obesity paradox in cardiovascular diseases. Progress in Cardiovascular Diseases. 2023; 78: 2-10.
  • 5. Keleş V, Büyükgüzel K, Büyükgüzel E. Leptin ve Metabolik Düzenlenmedeki Rolü. Türkiye Diyabet ve Obezite Dergisi. 2018; 2(1): 17-2
  • 6. Picó C, Palou M, Pomar CA, Rodríguez AM, Palou A. Leptin as a key regulator of the adipose organ. Reviews in Endocrine and Metabolic Disorders. 2022; 23(1): 13-30.
  • 7. Münzberg H, Singh P, Heymsfield SB, Yu S, Morrison CD. Recent advances in understanding the role of leptin in energy homeostasis. F1000Research. 2020; 9.
  • 8. Boucsein A, Kamstra K, Tups A. Central signalling cross‐talk between insulin and leptin in glucose and energy homeostasis. Journal of Neuroendocrinology. 2021; 33(4): e12944.
  • 9. Simonds S, Pryor J, Cowley M. Leptin is a key regulator of glucose homeostasis in obesity. Physiology. 2023; 38(S1), 5793859.
  • 10. Tripathi D, Kant S, Pandey S, Ehtesham NZ. Resistin in metabolism, inflammation, and disease. The FEBS journal. 2020; 287(15): 3141-3149.
  • 11. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR. et al. The hormone resistin links obesity to diabetes. Nature. 2001; 409(6818): 307-312.
  • 12. Filková M, Haluzík M, Gay S, Šenolt L. The role of resistin as a regulator of inflammation: Implications for various human pathologies. Clinical immunology. 2009; 133(2): 157-170.
  • 13. Jamaluddin MS, Weakley SM, Yao Q, Chen C. Resistin: functional roles and therapeutic considerations for cardiovascular disease. British journal of pharmacology. 2012; 165(3): 622-632.
  • 14. Liu J, Cao J, Li Y, Guo F. Beneficial flavonoid in foods and anti-obesity effect. Food Reviews International. 2023; 39(1), 560-600.
  • 15. Al-Ishaq RK, Abotaleb M, Kubatka P, Kajo K, Büsselberg D. Flavonoids and their anti-diabetic effects: Cellular mechanisms and effects to improve blood sugar levels. Biomolecules. 2019; 9(9): 430.
  • 16. Alvesalo J, Vuorela H, Tammela P, Leinonen M, Saikku P, Vuorela P. Inhibitory effect of dietary phenolic compounds on Chlamydia pneumoniae in cell cultures. Biochemical pharmacology. 2006; 71(6): 735-741.
  • 17. Li C, Schluesener H. Health-promoting effects of the citrus flavanone hesperidin. Critical reviews in food science and nutrition. 2017; 57(3): 613-631.
  • 18. Kawser Hossain M, Abdal Dayem A, Han J, Yin Y, Kim K, Kumar Saha S, et al. Molecular mechanisms of the anti-obesity and anti-diabetic properties of flavonoids. International journal of molecular sciences. 2016; 17(4): 569.
  • 19. Oliveira AKDS, de Oliveira e Silva AM, Pereira RO, Santos AS, Barbosa Junior EV, Bezerra MT. et al. Anti-obesity properties and mechanism of action of flavonoids: A review. Critical Reviews in Food Science and Nutrition. 2022; 62(28): 7827-7848.
  • 20. Song D, Cheng L, Zhang X, Wu Z, Zheng X. The modulatory effect and the mechanism of flavonoids on obesity. Journal of food biochemistry. 2019; 43(8): e12954.
  • 21. Joshi H, Vastrad B, Joshi N, Vastrad C, Tengli A, Kotturshetti I. Identification of key pathways and genes in obesity using bioinformatics analysis and molecular docking studies. Frontiers in Endocrinology. 2021; 12: 628907.
  • 22. Panghiyangani R, Utami JP, Baitullah MA, Maulida ND. Molecular Docking of Citrus amblycarpa Active Compounds against FTO, Leptin, and Resistin Protein. Molecular and Cellular Biomedical Sciences. 2023; 7(1): 38-46.
  • 23. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry. 2010; 31(2): 455-461.
  • 24. Zhang F, Basinski MB, Beals JM, Briggs SL, Churgay LM, Clawson DK, et al. Crystal structure of the obese protein Ieptin-E100. Nature. 1997; 387(6629): 206-209.
  • 25. Patel SD, Rajala MW, Rossetti L, Scherer PE, Shapiro L. Disulfide-dependent multimeric assembly of resistin family hormones. Science. 2004; 304(5674): 1154-1158.
  • 26. Biovia DS, Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Richmond TJ. Dassault systèmes BIOVIA, discovery studio visualizer, v. 17.2, San Diego: Dassault Systèmes, 2016. J Chem Phys. 2000; 10: 21-9991.
  • 27. Strømgaard K, Krogsgaard-Larsen P, Madsen U. Textbook of Drug Design and Discovery. 5th ed. Boca Raton: CRC Press; 2017.
  • 28. Sousa JN, Queiroz LDRP, de Paula AMB, Guimarães ALS, Lescano CH, Aguilar CM, et al. Gallic acid as a Sestrin (SESN2) activator and potential obesity therapeutic agent: A molecular docking study. Gene. 2023; 883: 147683.
  • 29. Rufino AT, Costa VM, Carvalho F, Fernandes E. Flavonoids as antiobesity agents: A review. Medicinal Research Reviews. 2021; 41(1): 556-585.
  • 30. García-Barrado MJ, Iglesias-Osma MC, Pérez-García E, Carrero S, Blanco EJ, Carretero-Hernández M, Carretero J. Role of flavonoids in the interactions among obesity, inflammation, and autophagy. Pharmaceuticals. 2020; 13(11): 342.
  • 31. Liu Y, Fu X, Lan N, Li S, Zhang J, Wang S, et al. Luteolin protects against high fat diet-induced cognitive deficits in obesity mice. Behavioural brain research. 2014; 267: 178-188.
  • 32. Kwon EY, Jung UJ, Park T, Yun JW, Choi MS. Luteolin attenuates hepatic steatosis and insulin resistance through the interplay between the liver and adipose tissue in mice with diet-induced obesity. Diabetes. 2015; 64(5): 1658-1669.
  • 33. Sundaram R, Shanthi P, Sachdanandam P. Effect of tangeretin, a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats. Phytomedicine. 2014; 21(6): 793-799.
  • 34. Zang Y, Zhang L, Igarashi K, Yu C. The anti-obesity and anti-diabetic effects of kaempferol glycosides from unripe soybean leaves in high-fat-diet mice. Food & function. 2015; 6(3): 834-841.
  • 35. Luo C, Yang H, Tang C, Yao G, Kong L, He H, Zhou Y. Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats. International Immunopharmacology. 2015; 28(1): 744-750.
There are 35 citations in total.

Details

Primary Language Turkish
Subjects Pharmaceutical Biochemistry
Journal Section Research Article
Authors

Serkan Sugeçti 0000-0003-3412-2367

Early Pub Date September 3, 2024
Publication Date August 31, 2024
Submission Date March 22, 2024
Acceptance Date August 31, 2024
Published in Issue Year 2024 Volume: 10 Issue: 2

Cite

APA Sugeçti, S. (2024). Bazı Flavonoidlerin Leptin ve Resisitin Proteinleri ile Etkileşimlerinin Moleküler Kenetlenme (Docking) Yöntemiyle İncelenmesi. International Anatolia Academic Online Journal Health Sciences, 10(2), 335-348.

International Anatolia Academic Online Journal Health Sciences