Abstract
The anti-obesity potential of various plant extracts and their associated bioactive compounds is well known. Molecular docking studies of FTO with flavonoids, using Orlistat (an anti-obesity drug) as a control, were performed to identify the effects of Rhamnus’ flavonoids with FTO (Obesity and obesity associated protein). Prior to molecular docking simulation, Rhamnus flavanoids were analysed using AutoDockTools (version 1.5.6). Docking simulations of the interaction of Rhamnus flavanoids with FTO were performed using AutoDock Vina version 1.1.2. Their binding affinities were obtained. BIOVIA Discovery Studio software was used to visualise the interaction between receptor and ligand. Our study approved the binding ability to FTO protein, and the affinity was as Aloe Emodin Dimer>Emodin>6-Methoxysorigenin. As a results, Rhamnus flavonoids have the remarkable ability to FTO protein, which means they are potent molecules as a potent FTO-inhibitor. Interestingly, Orlistat has lower affinity than Aloe-emodin dimer (-8.7 vs -10.8), which means aloe-emodin dimer more potent to bound the active site. In contrast, two other Rhamnnus flavonoids were shown lower binding affinity when compared to Orlistat.In conclution, Rhmanus phytomolecules able to bind to the catalytic site of FTO as well as “Orlistat” has been demonstrated by molecular docking. Thus, Rhamnus flavonoids especially “Aloe-emodin dimer” is a potent molecule to develop “anti-obesity drug”.
Supporting Institution
none
Project Number
None
Thanks
None
References
- Bouhlel Chatti, I., Ben Toumia, I., Krichen, Y., Maatouk, M., Chekir Ghedira, L., & Krifa, M. (2022). Assessment of Rhamnus alaternus Leaves Extract: Phytochemical Characterization and Antimelanoma Activity. Journal of medicinal food, 25(9), 910–917.
- Chen, J., Wan, C. M., Gong, S. T., Fang, F., Sun, M., Qian, Y., Huang, Y., Wang, B. X., Xu, C. D., Ye, L. Y., Dong, M., Jin, Y., Huang, Z. H., Wu, Q. B., Zhu, C. M., Fang, Y. H., Zhu, Q. R., & Dong, Y. S. (2018). Chinese clinical practice guidelines for acute infectious diarrhea in children. World journal of pediatrics : WJP, 14(5), 429–436.
- Khuda, F., Alam, N., Khalil, A. A. K., Jan, A., Naureen, F., Ullah, Z., Alotaibi, A., Ullah, R., Ullah, S., Shah, Y., Shah, S. I., & Büyüker, S. M. (2022). Screening of Rhamnus Purpurea (Edgew.) Leaves for Antimicrobial, Antioxidant, and Cytotoxic Potential. ACS omega, 7(26), 22977–22985.
- Hardinsyah, H., Gunawan, W.B., Nurkolis, F., Alisaputra, D. Kurniawan, R. Mayulu, N. Taslim, N. A. & Tallei, T.E. (2023) Antiobesity potential of major metabolites from Clitoria ternatea kombucha: Untargeted metabolomic profiling and molecular docking simulations," 6, pp. 100464.
- Mohammed, A., Al-Numair, K. S., & Balakrishnan, A. (2015). Docking studies on the interaction of flavonoids with fat mass and obesity associated protein. Pakistan journal of pharmaceutical sciences, 28(5), 1647–1653.
- Peters, U., North, K. E., Sethupathy, P., Buyske, S., Haessler, J., Jiao, S., Fesinmeyer, M. D., Jackson, R. D., Kuller, L. H., Rajkovic, A., Lim, U., Cheng, I., Schumacher, F., Wilkens, L., Li, R., Monda, K., Ehret, G., Nguyen, K. D., Cooper, R., Lewis, C. E., … Kooperberg, C. (2013). A systematic mapping approach of 16q12.2/FTO and BMI in more than 20,000 African Americans narrows in on the underlying functional variation: results from the Population Architecture using Genomics and Epidemiology (PAGE) study. PLoS genetics, 9(1), e1003171.
- Scuteri, A., Sanna, S., Chen, W. M., Uda, M., Albai, G., Strait, J., Najjar, S., Nagaraja, R., Orrú, M., Usala, G., Dei, M., Lai, S., Maschio, A., Busonero, F., Mulas, A., Ehret, G. B., Fink, A. A., Weder, A. B., Cooper, R. S., Galan, P., … Abecasis, G. R. (2007). Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS genetics, 3(7), e115.
- Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry, 31(2), 455–461.
- van Dijk, S. J., Molloy, P. L., Varinli, H., Morrison, J. L., Muhlhausler, B. S., & Members of EpiSCOPE (2015). Epigenetics and human obesity. International journal of obesity (2005), 39(1), 85–97.
Abstract
Çeşitli bitki özlerinin ve bunların içeriğindeki biyoaktif bileşiklerin obeziteye karşı potansiyeli iyi bilinmektedir. Flavonoidlerin obezite ve obezite ile ilişkili protein (FTO) ile ilişkisinin mekanizmasını keşfetmek için kontrol olarak Orlistat (obezite karşıtı bir ilaç) kullanılarak FTO'nun flavonoidlerle moleküler kenetlenme çalışmaları yapılmıştır. Moleküler kenetlenme simülasyonundan önce, Rhamnus flavanoidleri AutoDockTools (sürüm 1.5.6) kullanılarak analiz edilmiştir. Rhamnus flavanoidlerinin FTO ile etkileşiminin docking simülasyonları AutoDock Vina versiyon 1.1.2 kullanılarak gerçekleştirilmiştir. Bağlanma afiniteleri elde edilmiştir. Reseptör ve ligand arasındaki etkileşimi görselleştirmek için BIOVIA Discovery Studio yazılımı kullanılmıştır. Çalışmamız FTO proteinine bağlanma yeteneğini çalışılan Rhamnus’a özgü flavanoidler için Aloe Emodin Dimer>Emodin>6-Methoxysorigenin olarak bulundu. Sonuç olarak, Rhamnus flavonoidleri FTO proteinine dikkat çekici bir bağlanma affinitesine sahiptir, bu da güçlü bir FTO inhibitörü olarak aday moleküller olabilecekleri anlamına gelir. İlginç bir şekilde, Orlistat, Aloe-emodin dimerinden daha düşük afiniteye sahiptir (-8.7 vs -10.8), bu da aloe-emodin dimerinin aktif bölgeye bağlanmak için daha güçlü olduğu anlamına gelir. Buna karşılık, diğer iki Rhamnnus flavonoidi Orlistat ile karşılaştırıldığında daha düşük bağlanma afinitesi göstermiştir. Sonuç olarak, Rhmanus fitomoleküllerinin FTO'nun katalitik bölgesine "Orlistat" kadar bağlanabildiği moleküler yerleştirme ile gösterilmiştir. Bu nedenle, Rhamnus flavonoidleri, özellikle "Aloe-emodin dimer", "obezite karşıtı ilaç" geliştirmek için güçlü bir moleküldür.
Project Number
None
References
- Bouhlel Chatti, I., Ben Toumia, I., Krichen, Y., Maatouk, M., Chekir Ghedira, L., & Krifa, M. (2022). Assessment of Rhamnus alaternus Leaves Extract: Phytochemical Characterization and Antimelanoma Activity. Journal of medicinal food, 25(9), 910–917.
- Chen, J., Wan, C. M., Gong, S. T., Fang, F., Sun, M., Qian, Y., Huang, Y., Wang, B. X., Xu, C. D., Ye, L. Y., Dong, M., Jin, Y., Huang, Z. H., Wu, Q. B., Zhu, C. M., Fang, Y. H., Zhu, Q. R., & Dong, Y. S. (2018). Chinese clinical practice guidelines for acute infectious diarrhea in children. World journal of pediatrics : WJP, 14(5), 429–436.
- Khuda, F., Alam, N., Khalil, A. A. K., Jan, A., Naureen, F., Ullah, Z., Alotaibi, A., Ullah, R., Ullah, S., Shah, Y., Shah, S. I., & Büyüker, S. M. (2022). Screening of Rhamnus Purpurea (Edgew.) Leaves for Antimicrobial, Antioxidant, and Cytotoxic Potential. ACS omega, 7(26), 22977–22985.
- Hardinsyah, H., Gunawan, W.B., Nurkolis, F., Alisaputra, D. Kurniawan, R. Mayulu, N. Taslim, N. A. & Tallei, T.E. (2023) Antiobesity potential of major metabolites from Clitoria ternatea kombucha: Untargeted metabolomic profiling and molecular docking simulations," 6, pp. 100464.
- Mohammed, A., Al-Numair, K. S., & Balakrishnan, A. (2015). Docking studies on the interaction of flavonoids with fat mass and obesity associated protein. Pakistan journal of pharmaceutical sciences, 28(5), 1647–1653.
- Peters, U., North, K. E., Sethupathy, P., Buyske, S., Haessler, J., Jiao, S., Fesinmeyer, M. D., Jackson, R. D., Kuller, L. H., Rajkovic, A., Lim, U., Cheng, I., Schumacher, F., Wilkens, L., Li, R., Monda, K., Ehret, G., Nguyen, K. D., Cooper, R., Lewis, C. E., … Kooperberg, C. (2013). A systematic mapping approach of 16q12.2/FTO and BMI in more than 20,000 African Americans narrows in on the underlying functional variation: results from the Population Architecture using Genomics and Epidemiology (PAGE) study. PLoS genetics, 9(1), e1003171.
- Scuteri, A., Sanna, S., Chen, W. M., Uda, M., Albai, G., Strait, J., Najjar, S., Nagaraja, R., Orrú, M., Usala, G., Dei, M., Lai, S., Maschio, A., Busonero, F., Mulas, A., Ehret, G. B., Fink, A. A., Weder, A. B., Cooper, R. S., Galan, P., … Abecasis, G. R. (2007). Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS genetics, 3(7), e115.
- Trott, O., & Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry, 31(2), 455–461.
- van Dijk, S. J., Molloy, P. L., Varinli, H., Morrison, J. L., Muhlhausler, B. S., & Members of EpiSCOPE (2015). Epigenetics and human obesity. International journal of obesity (2005), 39(1), 85–97.
Details
| Primary Language | English |
|---|---|
| Subjects | Engineering |
| Journal Section | Articles |
| Authors | |
| Project Number | None |
| Early Pub Date | March 25, 2023 |
| Publication Date | March 31, 2023 |
| Published in Issue | Year 2023 Issue: 49 |
