Action of Cyanidin-3-Glucoside on Anti-obesity: An In-silico Approach

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DOI: 10.21522/TIJPH.2013.SE.24.06.Art005

Authors : Kaviyarasi R, Gayathri R, Kavitha. S, Vishnu Priya Veeraraghavan, Aswin G

Abstract:

Cyanidin-3-glucoside (C3G), a flavonoid is present in berries and has anti-obesity properties. Understanding the mechanisms underlying its effects on metabolic pathways linked to obesity is vital to its therapeutic use. The aim of this study is to investigate the interaction of C3G with key metabolic proteins, including AMP-activated protein kinase (AMPK), Adiponectin receptor 1 (AdipoR1), and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), using in-silico methods. This in-silico study investigated C3G's binding affinities to AMPK, AdipoR1, and PGC1α using molecular docking simulations. Protein structures were created with Discovery Studio Visualizer 2020 and acquired from the Protein Data Bank. Using AutoDock 1.5.7, C3G was extracted from PubChem, its energy was reduced, and it was docked to the protein targets. Analysis was done on the root mean square deviation (RMSD) values, interaction types, and binding affinities. C3G had docking scores of -7.3, -7.3, and -7.8 kcal/mol for AMPK, AdipoR1, and PGC1α, respectively, indicating strong binding affinities. Pi-anion, pi-alkyl, and hydrogen bonding were all engaged in the interactions. Stable binding conformations were indicated by low RMSD values, indicating that C3G may influence energy management and lipid metabolism. The potential of C3G as an anti-obesity drug was suggested by its remarkable binding affinities with important metabolic proteins. Additional in vitro and in vivo investigations are required to confirm these results and investigate the potential therapeutic uses of C3G.

References:

[1].      Zad, O.D., Al-Dalali, S., Zhao, L., Zhao, L. and Wang, C., 2024. Recent advances on cyanidin-3-O-glucoside in preventing obesity-related metabolic disorders: A comprehensive review. Biochemical and Biophysical Research Communications, p.150344.

[2].      Agustin, A.T., Safitri, A. and Fatchiyah, F., 2020. An in-silico approach reveals the potential function of cyanidin-3-o-glucoside of red rice in inhibiting the advanced glycation end products (AGES)-receptor (RAGE) signaling pathway. Acta Informatica Medica, 28(3), p.170.

[3].      Guo, H., Xia, M., Zou, T., Ling, W., Zhong, R. and Zhang, W., 2012. Cyanidin 3-glucoside attenuates obesity-associated insulin resistance and hepatic steatosis in high-fat diet-fed and db/db mice via the transcription factor FoxO1. The Journal of Nutritional Biochemistry, 23(4), pp.349-360.

[4].      Hirshasri, A.G., Renu, K., Priya, V.V., Gayathri, R. and Kavitha, S., The Effect of Aspalathin on SMAD2, SMAD3, TGF-β-A Major Contributor of Inflammation–An In-silico Approach. DOI: 10.21522/TIJPH.2013.SE.24.01.Art009.

[5].      Su, P., Veeraraghavan, V.P., Krishna Mohan, S. and Lu, W., 2019. A ginger derivative, zingerone—a phenolic compound—induces ROS‐mediated apoptosis in colon cancer cells (HCT‐116). Journal of biochemical and molecular toxicology, 33(12), p.e22403. DOI: 10.1002/jbt.22403.

[6].      Jayaraman, S., Krishnamoorthy, K., Prasad, M., Veeraraghavan, V.P., Krishnamoorthy, R., Alshuniaber, M.A., Gatasheh, M.K. and Elrobh, M., 2023. Glyphosate potentiates insulin resistance in skeletal muscle through the modulation of IRS-1/PI3K/Akt mediated mechanisms: an in vivo and in silico analysis. International Journal of Biological Macromolecules, 242, p.124917.

[7].      Rajendran, P., Renu, K., Abdallah, B.M., Ali, E.M., Veeraraghavan, V.P., Sivalingam, K., Rustagi, Y., Abdelsalam, S.A., Ibrahim, R.I.H. and Al-Ramadan, S.Y., 2024. Nimbolide: promising agent for prevention and treatment of chronic diseases (recent update). Food & Nutrition Research, 68. DOI: 10.29219/fnr.v68.9650

[8].      Roy, J.R., Janaki, C.S., Jayaraman, S., Veeraraghavan, V.P., Periyasamy, V., Balaji, T., Vijayamalathi, M., Bhuvaneswari, P. and Swetha, P., 2023. Hypoglycemic potential of carica papaya in liver is mediated through IRS-2/PI3K/SREBP-1c/GLUT2 signaling in high-fat-diet-induced type-2 diabetic male rats. Toxics, 11(3), p.240. DOI: 10.3390/toxics11030240

[9].      Ponnusamy, B., Veeraraghavan, V.P., Al-Huseini, I., Woon, C.K., Jayaraman, S. and Sirasanagandla, S.R., 2024. Heavy Metal Exposure-Induced Cardiovascular Diseases: Molecular Mechanisms and Therapeutic Role of Antioxidants. Current Medicinal Chemistry. DOI: 10.2174/0109298673307446240514064253.

[10].  Wondmkun, Y.T., 2020. Obesity, insulin resistance, and type 2 diabetes: associations and therapeutic implications. Diabetes, Metabolic Syndrome and Obesity, pp.3611-3616.

[11].   Kannan, B. and Arumugam, P., 2023. The implication of mitochondrial DNA mutation and dysfunction in periodontal diseases. Journal of Indian Society of Periodontology, 27(2), pp.126-130. DOI:10.4103/jisp.jisp_678_21.

[12].   Gomes, J.V.P., Rigolon, T.C.B., da Silveira Souza, M.S., Alvarez-Leite, J.I., Della Lucia, C.M., Martino, H.S.D. and Rosa, C.D.O.B., 2019. Antiobesity effects of anthocyanins on mitochondrial biogenesis, inflammation, and oxidative stress: A systematic review. Nutrition, 66, pp.192-202.

[13].  You, Y., Han, X., Guo, J., Guo, Y., Yin, M., Liu, G., Huang, W. and Zhan, J., 2018. Cyanidin-3-glucoside attenuates high-fat and high-fructose diet-induced obesity by promoting the thermogenic capacity of brown adipose tissue. Journal of Functional Foods, 41, pp.62-71.

[14].  Ngamsamer, C., Sirivarasai, J. and Sutjarit, N., 2022. The benefits of anthocyanins against obesity-induced inflammation. Biomolecules, 12(6), p.852.

[15].  Ahn, J., Lee, H., Kim, S., Park, J. and Ha, T., 2008. The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochemical and Biophysical Research Communications, 373(4), pp.545-549.

[16].  Bartel, I., Koszarska, M., Strzałkowska, N., Tzvetkov, N.T., Wang, D., Horbańczuk, J.O., Wierzbicka, A., Atanasov, A.G. and Jóźwik, A., 2023. Cyanidin-3-O-glucoside as a nutrigenomic factor in type 2 diabetes and its prominent impact on health. International Journal of Molecular Sciences, 24(11), p.9765.

[17].  Ye, X., Chen, W., Huang, X.F., Yan, F.J., Deng, S.G., Zheng, X.D. and Shan, P.F., 2024. Anti-diabetic effect of anthocyanin cyanidin-3-O-glucoside: data from insulin resistant hepatocyte and diabetic mouse. Nutrition & Diabetes, 14(1), p.7.

[18].  Khanna, N., Chokkattu, J.J., Neeharika, S., Ramakrishnan, M., Shanmugam, R. and Thangavelu, L., 2023. Anti-inflammatory Activity and Cytotoxic Effect of Ginger and Rosemary-mediated Titanium Oxide Nanoparticles-based Dental Varnish. World Journal of Dentistry, 14(9), pp.761-765. DOI: 10.5005/jp-journals-10015-2299.

[19].  Juvairiya Fathima, A., Renu, K., Priya, V.V., Gayathri, R. and Kavitha, S., Determining the Role of Caffeic Acid on Lipogenic Regulators: An In-Silico Approach. DOI:10.21522/TIJPH.2013.SE.24.01.Art012.

[20].  Aarthi, L., Renu, K., Priya, V.V., Gayathri, R. and Kavitha, S., Molecular Docking Analysis of Epigallocatechin 3-Gallate [EGCG] on Fatty Acids and Carnitine Transporters Family. Doi: 10.21522/TIJPH.2013.SE.24.01.Art010.

[21].  Deepa, P., Hong, M., Sowndhararajan, K. and Kim, S., 2023. A Review of the Role of an Anthocyanin, Cyanidin-3-O-β-glucoside in Obesity-Related Complications. Plants, 12(22), p.3889.

[22].  Wang, Q., Xia, M., Liu, C., Guo, H., Ye, Q., Hu, Y., Zhang, Y., Hou, M., Zhu, H., Ma, J. and Ling, W., 2008. Cyanidin-3-O-β-glucoside inhibits iNOS and COX-2 expression by inducing liver X receptor alpha activation in THP-1 macrophages. Life Sciences, 83(5-6), pp.176-184.

[23].  Fu, Y., Wei, Z., Zhou, E., Zhang, N. and Yang, Z., 2014. Cyanidin-3-O-β-glucoside inhibits lipopolysaccharide-induced inflammatory response in mouse mastitis model. Journal of Lipid Research, 55(6), pp.1111-1119.

[24].  Zhu, L., Cao, F., Hu, Z., Zhou, Y., Guo, T., Yan, S., Xie, Q., Xia, X., Yuan, H., Li, G. and Luo, F., 2024. Cyanidin-3-O-Glucoside Alleviates Alcoholic Liver Injury via Modulating Gut Microbiota and Metabolites in Mice. Nutrients, 16(5), p.694.

[25].  Lumeng, C.N., Deyoung, S.M. and Saltiel, A.R., 2007. Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins. American Journal of Physiology-Endocrinology and Metabolism, 292(1), pp.E166-E174.

[26].  Seymour, E.M., Lewis, S.K., Urcuyo-Llanes, D.E., Tanone, I.I., Kirakosyan, A., Kaufman, P.B. and Bolling, S.F., 2009. Regular tart cherry intake alters abdominal adiposity, adipose gene transcription, and inflammation in obesity-prone rats fed a high fat diet. Journal of Medicinal Food, 12(5), pp.935-942.

[27].  Serra, D., Paixão, J., Nunes, C., Dinis, T.C. and Almeida, L.M., 2013. Cyanidin-3-glucoside suppresses cytokine-induced inflammatory response in human intestinal cells: comparison with 5-aminosalicylic acid. PloS one, 8(9), p.e73001.

[28].  Rajasekar, A. and Ganapathy, D., 2023. Effectiveness of nonsurgical periodontal therapy on salivary visfatin: a clinical and biochemical analysis. World J Dentistry, 14, p.75. Doi: 10.5005/jp-journals-10015-2176.

[29].  Rajasekar, A., 2023. Correlation of salivary visfatin levels in obese and NON-OBESE population with periodontal status. Journal of oral biology and craniofacial research, 13(1), pp.67-70. https://doi.org/10.1016/j.jobcr.2022.11.004.

[30].  Krishnan, R.P., Ramani, P., Pandiar, D. and Dinesh, Y., 2023. Gingival swelling as a first sign of clinical presentation of ligneous periodontitis in a patient with autism spectrum disorder. The Journal of the American Dental Association, 154(5), pp.427-431. doi: 10.1016/j.adaj.2022.12.005.

[31].   Kaarthikeyan, G., Jayakumar, N.D. and Sivakumar, D., 2019. Comparative Evaluation of Bone Formation between PRF and Blood Clot Alone as the Sole Sinus-Filling Material in Maxillary Sinus Augmentation with the Implant as a Tent Pole: A Randomized Split-Mouth Study. Journal of long-term effects of medical implants, 29(2).

[32].  Kavarthapu, A. and Malaiappan, S., 2019. Comparative evaluation of demineralized bone matrix and type II collagen membrane versus eggshell powder as a graft material and membrane in rat model. Indian Journal of Dental Research, 30(6), pp.877-880.

[33].  Manchery, N., John, J., Nagappan, N., Subbiah, G.K. and Premnath, P., 2019. Remineralization potential of dentifrice containing nanohydroxyapatite on artificial carious lesions of enamel: A comparative: in vitro: study. Dental research journal, 16(5), pp.310-317.

[34].  Frountzas, M., Karanikki, E., Toutouza, O., Sotirakis, D., Schizas, D., Theofilis, P., Tousoulis, D. and Toutouzas, K.G., 2023. Exploring the Impact of Cyanidin-3-Glucoside on Inflammatory Bowel Diseases: Investigating New Mechanisms for Emerging Interventions. International Journal of Molecular Sciences, 24(11), p.9399.

[35].  Oliveira, H., Fernandes, A., F. Brás, N., Mateus, N., de Freitas, V. and Fernandes, I., 2020. Anthocyanins as antidiabetic agents—in vitro and in-silico approaches of preventive and therapeutic effects. Molecules, 25(17), p.3813.