Assessment of the Effect of Flavonoids Biomolecules on Fat Mass and Obesity Associated (FTO) Protein as Anti-Obesity Agents: An <i>In-Silico</i> Study


  • Alexander Idoko Department of Biochemistry, Faculty of Natural Sciences, Caritas University, Amorji-Nike, PMB 01784 Enugu, Nigeria
  • Elijah J. Parker Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Nigeria
  • Obioma U. Njoku Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Nigeria



Obesity, Ligands, Flavonoids, Biomolecule, Binding affinity, Anti-obesity


Recent studies on the management of obesity are centered on the ability of small compounds to modulate fat mass and obesity-associated protein (FTO). This study is aimed at investigating the inhibitory effects of flavonoid biomolecules on fat mass and obesity-associated protein (FTO) in silico. The studied ligands from methanol flavonoid-rich fraction of lime juice (MFLJ) and ethylacetate flavonoid-rich fraction of honey (EAFH) include quercetin, Epigallocatechin, p-Coumarin, Caffeic acid, Naphthoresorcinol, Gallic acid, and Sinapic acid. The ligands were characterized using high-performance liquid chromatography (HPLC). Molecular docking of the ligands and the FTO protein was performed using AutoDock Vina software. Results show that Ser-229, Tyr-108, Asp-233, and Glu-234 are the catalytic sub-units of the FTO protein, which were essential in hydrogen bond formation and interactions between ligands and the FTO protein. The ΔG value of binding affinity for all ligands revealed their potential as inhibitors of FTO protein. Quercetin (-8.2 Kcal/mol), epigallocatechin (-8.0 Kcal/mol), and p-coumarin (-7.3 Kcal/mol) possessed the highest inhibitory effect on the fat mass and obesity-associated (FTO) protein compared to the standard drugs (atorvastatin: -7.5 Kcal/mol and orlistat: -6.6 Kcal/mol). In conclusion, quercetin, epigallocatechin, and p-coumarin exhibited the highest inhibitory effect against FTO protein. This reveals their potential as anti-obesity agents that could be used in the treatment of obesity.

Author Biography

Alexander Idoko, Department of Biochemistry, Faculty of Natural Sciences, Caritas University, Amorji-Nike, PMB 01784 Enugu, Nigeria

Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Nigeria


Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K. Health effects of overweight and obesity in 195 countries over 25 years. The New Eng J Med. 2017; 377(1):13–27.

Chen X, Zhang Z, Yang H, Qiu P, Wang H, Wang F. Consumption of ultra-processed foods and health outcomes: a systematic review of epidemiological studies. Nutr J. 2020; 19(1):86.

Davies KM, Heaney RP, Recker RR, Lappe JM, Barger-Lux MJ, Rafferty K, Hinders S. Calcium intake and body weight. J Clin Endo Metabo. 2000; 85(12):4635–4638.

Blüher M. Obesity: Global epidemiology and pathogenesis. Nat Rev Endo. 2019; 15:288–298.

Salvestrini V, Sell C, Lorenzini A. Obesity May Accelerate the Aging Process. Front Endocrinol. 2019; 10(266):1-16.

Shutting G, Xitong L, Miao Z, Ning Z, Ruiyong W, Junbiao C. Structural characteristics of small-molecule inhibitors targeting FTO demethylase. Fut Med Chem. 2021; 13:17.

Lan N, Lu Y, Shuangshuang P, Xi H, Nie X, Liu J, Wenzhen, Y. FTO-a common genetic basis for obesity and cancer. Front Gen. 2020; 11(559138):1-12.

Sumaryada T, Simamora REM, Ambarsari L. Docking Evaluation of Catechin and its Derivatives on Fat Mass and Obesity-Associated (FTO) Protein For Anti-Obesity Agent. J Appl Pharm Sci. 2018; 8(08):063-068.

Sudeep HV and Shyam PK. Computational studies on the antiobesity effect of polyphenols from pomegranate leaf. J Chem Pharm Res. 2014; 6(9):278-281.

Kumar R, Ningombam SS, Kumar R, Goel H, Gogia A, Khurana S, Deo SVS, Mathur S and Tanwar P. Comprehensive mutations analyses of FTO (fat mass and obesity-associated gene) and their effects on FTO’s substrate binding implicated in obesity. Front Nutr. 2022; 9:852944.

Danila C, Tamara YF, Sadia A, Massimiliano G, Patricia R, Piera PM, Jiaojiao Z, Leire BL, Susana MF, Pablo AT. Phenolic Compounds in Honey and Their Associated Health Benefits: A Review. Molecule 2018; 23(2322):1-20.

Natasha LH, Ujang T, Benjamin LLT, Madeleine F, Mary TF. Mineral and Trace Element Analysis of Australian/Queensland Apis mellifera Honey. Int J Env Res Pub Health. 2020; 17(6304):1-14.

Petretto GL, Cossu M, Alamanni MC. Phenolic content, antioxidant, and physicochemical properties of Sardinian monofloral honey. Int J Food Sci Technol. 2015; 50:482–491.

Ayman MM, Rene JHB, Mansur AS, Omnia EH. Beneficial Effects of Citrus Flavonoids on Cardiovascular and Metabolic Health. Oxid Med Cell Longev. 2019; 2019:5484138.

Mariarosaria B and Stefania D. Anti-Obesity Effects of Polyphenol Intake: Current Status and Future Possibilities. Int J Mol Sci. 2020; 20(5642):1-24.

Ali EA. Nutritional value and pharmacological importance of citrus species grown in Iraq. IOSR J Phar. 2016; 6(8):76-108.

Idoko A, Ikpe VPO, Nelson NO, Effiong JU, Alhassan AJ, Muhammad IU, Abubakar N, Abubakar SM. Effects of Lime Juice and Honey on Lipid Profile of Cholesterol Enriched Diet Fed Rat Model. Ann Res Rev Biol. 2017; 20(3):1-10.

Idoko A, Parker JE, Njoku O U. Ethylacetate Flavonoid Biocompounds of Honey with Mitigating Anti-hyperlipidemic and Antioxidant Properties in Carbohydrate and Lipid Enriched Diets – Obese Rats. Ann Res Rev Biol. 2023; 38(9):1-23.

Idoko A, Parker JE, Njoku OU, Ifeanyi ED, Victor EJ, Ugwudike PO, Jennifer NC. Acute toxicity and hepato-renal protection of lime juice, honey and their flavonoid-rich fractions in high fat-diet induced obese rat model. Univ J Pharm Res. 2023; 8(6):23-31.

Nur ZR, Kok-Yong C, Khairul AZ, Fairus A. A Review on the Protective Effects of Honey against Metabolic Syndrome. Nutr. 2018; 10 (1009):1-21.

Bukola CA, Temitayo OA, Olubusola AO. Phytochemical Composition and Comparative Evaluation of Antimicrobial Activities of the Juice Extract of Citrus aurantifolia and its Silver Nanoparticles. Nig J Pharma Res. 2016; 12(1):59-64.

Alamri M, Khalid SN, Aristatile B. Docking studies on the interaction of flavonoids with fat mass and obesity-associated protein. Pak J Pharm Sci. 2015; 28(5):1647-1653.

Wang Z, Wang N, Han X, Wang R, Chang J. Interaction of two flavonols with fat mass and obesity-associated protein investigated by fluorescence quenching and molecular docking. J Biomol Struct Dyn. 2018; 36(13):3388-3397.

Zhang L, Re T, Wang Z, Wang R, Chang J. Lambert JD, Ju J, Lu G, Sang S. Comparative study of the binding of 3 flavonoids to the fat mass and obesity-associated protein by spectroscopy and molecular modeling. J Mol Recog. 2017; 30:e2606.

Ren T, Zhang L, Wang J, Song C, Wang R, Chang J. Study on the interaction of taiwaniaquinoids with FTO by spectroscopy and molecular modeling. J Biomol Struct Dyn. 2017; 35(14):3182-3193.

DeLano WL. The PyMOL Molecular Graphics System. Delano Scientific, San Carlos. 2002.

MOE (The Molecular Operating Environment) (2015) Chemical Computing Group Inc. Available from:

Trott O and Olson AJ. AutoDock Vina : Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading. J Comp Chem. 2010; 31(2): 455–461.

Daina A, Michielin O, Zoete V. SwissADME : a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017; 7:42717.

Soria AC, Martínez-Castro I, Sanz J. Analysis of the volatile composition of honey by solid-phase microextraction and gas chromatography-mass spectrometry. J Sep Sci. 2003; 26:793-801.

Manyi-Loh CE, Clarke AM, Roland NN. An overview of honey: Therapeutic properties and contribution in nutrition and human health. Afr J Micr Res. 2010; 5(8):844-852.

Fuad A, Fadi A, Wael AA, Hammad KA, Saleh A, Ghassab MA, Haya JAS. HPLC Analysis of Chemical Composition of Selected Jordanian Medicinal Plants and their Bioactive Properties. Orien J Chem. 2018; 34(5):2397-2403.

Aja P, Agu P, Ezeh E, Awoke J, Ogwoni H, Deusdedit T, Ekpono E, Igwenyi I, Alum E, Ugwuja E. Prospect into therapeutic potentials of Moringa oleifera phytocompounds against cancer upsurge: de novo synthesis of test compounds, molecular docking, and ADMET studies. Bull Nat Res Cent. 2021; 45(1):1–1.

Lipinski CA. Lead-and drug-like compounds: the rule-of-five revolution. Drug Disc Today Techn. 2004; 1(4):337–341.

Tony S, Renti E, Marimpola S, Laksmi A. Docking Evaluation of Catechin and its Derivatives on Fat Mass and Obesity-Associated (FTO) Protein For Anti-Obesity Agent. J Appl Pharm Sci. 2018; 8(08):063-068.

Merra G, Gualtieri P, Cioccoloni G, Falco S, Bigioni G, Tarsitano M. Fto rs9939609 influence on adipose tissue localization in the Italian population. Eur Rev Med Pharm Sci. 2020; 24:3223–3235.

Arunkumar EA and Sushil KJ. Adiponectin is a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int J Mol Sci. 2017; 18(6):1321.

Shuang C, Hongmei J, Xiaosong W, Jun F. Therapeutic Effects of Quercetin on Inflammation, Obesity, and Type 2 Diabetes. Mediators Inflamm. 2016; 2016:9340637.

Wang S, Sun Z, Dong S, Liu Y, Liu Y. Molecular interactions between (−)-epigallocatechin gallate analogs and pancreatic lipase. PLoS ONE. 2014; 9:e111143.

Choi C, Hyun-Doo S, Yeonho S, Yoon KC, Sang-Yeop A, Young-Suk J, Young CY, Sung WK, Yun-Hee L. Epigallocatechin-3-Gallate Reduces Visceral Adiposity Partly through the Regulation of Beclin1-Dependent Autophagy in White Adipose Tissues. Nutr. 2020; 12(10):3072.

Manisha S, Thilini T, Ravi S, Benu A. Managing obesity through natural polyphenols: A review. Fut Foods. 2020; 1–2:100002

Chin-Lin H, Gow-Chin Y. Effect of gallic acid on high fat diet-induced dyslipidemia, hepatosteatosis, and oxidative stress in rats. The Brit J Nutr. 2007; 98(4):727-735.

Sandra TD. Prostaglandin H Synthase and Vascular Function. Circ Res. 2001; 89:650–660.

Perticone F, Ceravolo R, Candigliota M, Ventura G, Iacopino S, Sinopoli F, Mattioli PL. Obesity and body fat distribution induce endothelial dysfunction by oxidative stress: protective effect of vitamin C. Diabetes. 2001; 50:159–165.

Noon JP, Walker BR, Hand MF, Webb DJ. Impairment of forearm vasodilatation to acetylcholine in hypercholesterolemia is reversed by aspirin. Cardiovasc Res. 1998; 38:480–484.

Hussain S, Rehman AU, Luckett DJ, Blanchard CL, Obied HK, Strappe P. Phenolic compounds with antioxidant properties from Canola Meal extracts inhibit adipogenesis. Int J Mol Sci. 2019; 21(1):1.

Khaled MM and Islam BG. Sinapic acid restores blood parameters, serum antioxidants, and liver and kidney functions in obesity. J Diabetes Metab Dis. 2022; 21(1):293–303.

Esmail L, Patrick JB, Joaquim G, Encarnación C, Isabel N. Caffeic acid and hydroxytyrosol have anti-obesogenic properties in zebrafish and rainbow trout models. PLoS One. 2017; 12(6):e0178833.

Jia X, Jianbing G, Xiaoyun H, Yao S, Shujuan Z, Chuanhai Z, Wentao X, Kunlun H. Caffeic acid reduces body weight by regulating gut microbiota in diet-induced-obese mice. J Funct Foods. 2020; 74:104061.

Jazwa A, Jazwa U, Pietruczuk A, Jazwa M. The effect of honey on glucose metabolism-an in-silico approach. Molecule. 2016; 21(3), 348. doi:10.3390/molecules21030348

Tusubira D, Munezero J, Agu PC, Ajayi CC, Joseph OJ, Namale N, Ssedyabane F, Nakiguli CK, Abayomi EA, Aja PM. In-vivo and in-silico studies revealed the molecular mechanisms of Colocasia esculenta phenolics as novel chemotherapy against benign prostatic hyperplasia via inhibition of 5α-reductase and α1-adrenoceptor. In Silico Pharm. 2023; 11:4.

Cota D, Seeley RJ, Tschöp M. Neuroendocrine control of energy balance: a review of the evidence. The J Clin Endo Metab. 2006; 91(11):4256–4265.

Wang D, Wu Z, Zhou J, Zhang X. Rs9939609 polymorphism of the fat mass and obesity-associated (FTO) gene and metabolic syndrome susceptibility in the Chinese population: a meta-analysis. Endocrinol. 2020; 69:278–285.




How to Cite

Idoko, A., Parker, E. J., & Njoku, O. U. (2024). Assessment of the Effect of Flavonoids Biomolecules on Fat Mass and Obesity Associated (FTO) Protein as Anti-Obesity Agents: An <i>In-Silico</i> Study. Tropical Journal of Natural Product Research (TJNPR), 8(3), 6669–6680.