Nutrición Hospitalaria 03918 / http://dx.doi.org/10.20960/nh.03918
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Trabajo Original

Potential molecular mechanism of the Xiexin capsule in the intervention of dyslipidemia based on bioinformatics and molecular docking


Kunpeng Yao, Huzhi Cai, Yating Wang, Shuo Cheng, Qili Liu, Daoping Zhang, Qingyang Chen, Xinyu Chen

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Objective: bioinformatic methods and molecular docking technology were used to predict the active components, targets, and related biological pathways of the Xiexin capsule in the intervention for dyslipidemia, exploring its mechanism. Methods: the active components and targets of the Xiexin capsule were screened by the TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform )database. Genecards (The Human Gene Database), OMIM (Online Mendelian Inheritance in Man), PharmGkb (Pharmacogenomics Knowledge Base database), TTD (Therapeutic Target Database), and Drugbank platforms were used to search the disease targets of dyslipidemia. The Cytoscape 3.8.0 software was used to construct the 'component-target' network diagram, and the STRING (functional protein association networks) platform was used to analyze protein-protein interaction (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) enrichment analyses were performed by R language data packets to predict the mechanism of action. The AutoDockVina and PyMol software were used to dock the key active components in the Xiexin capsule and the core proteins in PPI. Results: a total of 66 effective components were screened, involving 114 targets; 87 key active compounds were screened from the 'drug-component-target' diagram. The PPI network mainly involved core proteins such as PTGS2 (prostaglandin-endoperoxide synthase 2), PTGS1 (prostaglandin-endoperoxide synthase 1), and HSP90AA1 (heat shock protein 90 alpha family class A member 1). GO and KEGG enrichment analysis results of common targets mainly involved hormone-mediated signaling pathway, steroid hormone response, lipid transport and metabolism, regulation of cholesterol storage, cyclooxygenase pathway, and other biological pathways, as well asMM PPAR (peroxisome proliferators-activated receptor) signaling pathway, IL-17 (interleukin 17) signaling pathway, PI3K-Akt (protein kinase b) signaling pathway, FcεRI signaling pathway, and other related pathways. Molecular docking verification showed that quercetin had the best binding with the core target protein HSP90AA1, and HSP90AA1 was the target protein with the best binding activity for the key chemical components in Xiexin capsules. Conclusion: the main chemical components in the Xiexin capsules may participate in the regulation of PPAR and other signaling pathways by regulating key genes such as ESR1 (estrogen receptor 1), MAPK14 (mitogen-activated protein kinase 14), and HSP90AA1, to exert the pharmacological effect of the intervention on dyslipidemia.

Palabras Clave: Xiexin capsule. Dyslipidemia. Bioinformatics. Molecular mechanism.



[1] A. L. Catapano, I. Graham, G. De Backer, et al., "2016 ESC/EAS Guidelines for the Management of Dyslipidaemias," Rev Esp Cardiol (Engl Ed), vol. 70, no. 2, pp. 115,2017
[2] S. E. Borggreve, R. De Vries, and R. P. Dullaart. "Alterations in high-density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus: role of lipolytic enzymes, lecithin:cholesterol acyltransferase and lipid transfer proteins," European Journal of Clinical Investigation, vol. 33, no. 12, pp. 1051-1069,2003
DOI: 10.1111/j.1365-2362.2003.01263.x
[3] H. Okazaki, T. Gotoda, M. Ogura, et al., "Current Diagnosis and Management of Primary Chylomicronemia," J Atheroscler Thromb, vol.,2021
DOI: 10.5551/jat.RV17054
[4] J. Miao, X. Zang, X. Cui, and J. Zhang. "Autophagy, Hyperlipidemia, and Atherosclerosis," Adv Exp Med Biol, vol. 1207, pp. 237-264,2020
DOI: 10.1007/978-981-15-4272-5_18
[5] P. Kraft, M. K. Schuhmann, C. Garz, et al., "Hypercholesterolemia induced cerebral small vessel disease," PloS One, vol. 12, no. 8, pp. e0182822,2017
DOI: 10.1371/journal.pone.0182822
[6] S. Choudhuri, P. K. Roy, B. Mitra, et al., "Hyperlipidemia-Mediated Increased Advanced Lipoxidation End Products Formation, an Important Factor Associated with Decreased Erythrocyte Glucose-6-Phosphate Dehydrogenase Activity in Mild Nonproliferative Diabetic Retinopathy," Can J Diabetes, vol. 41, no. 1, pp. 82-89,2017
DOI: 10.1016/j.jcjd.2016.07.007
[7] Y. L. Ma, H. Yao, W. J. Yang, X. X. Ren, L. Teng, and M. C. Yang. "Correlation between Traditional Chinese Medicine Constitution and Dyslipidemia: A Systematic Review and Meta-Analysis," Evidence-Based Complementary and Alternative Medicine, vol. 2017, pp. 1896746,2017
DOI: 10.1155/2017/1896746
[8] P. Hao, F. Jiang, J. Cheng, L. Ma, Y. Zhang, and Y. Zhao. "Traditional Chinese Medicine for Cardiovascular Disease: Evidence and Potential Mechanisms," Journal of the American College of Cardiology, vol. 69, no. 24, pp. 2952-2966,2017
DOI: 10.1016/j.jacc.2017.04.041
[9] A. L. Catapano, I. Graham, G. De Backer, et al., "2016 ESC/EAS Guidelines for the Management of Dyslipidaemias," European Heart Journal, vol. 37, no. 39, pp. 2999-3058,2016
DOI: 10.1093/eurheartj/ehw272
[10] Q. Zhang, J. Dong, and Z. Yu. "Pleiotropic use of Statins as non-lipid-lowering drugs," International Journal of Biological Sciences, vol. 16, no. 14, pp. 2704-2711,2020
DOI: 10.7150/ijbs.42965
[11] W. Zhang, Y. Huai, Z. Miao, A. Qian, and Y. Wang. "Systems Pharmacology for Investigation of the Mechanisms of Action of Traditional Chinese Medicine in Drug Discovery," Frontiers in Pharmacology, vol. 10, pp. 743,2019
DOI: 10.3389/fphar.2019.00743
[12] O. P. Ganda, D. L. Bhatt, R. P. Mason, M. Miller, and W. E. Boden. "Unmet Need for Adjunctive Dyslipidemia Therapy in Hypertriglyceridemia Management," Journal of the American College of Cardiology, vol. 72, no. 3, pp. 330-343,2018
DOI: 10.1016/j.jacc.2018.04.061
[13] E. D. Michos, C. T. Sibley, J. T. Baer, M. J. Blaha, and R. S. Blumenthal. "Niacin and statin combination therapy for atherosclerosis regression and prevention of cardiovascular disease events: reconciling the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial with previous surrogate endpoint trials," Journal of the American College of Cardiology, vol. 59, no. 23, pp. 2058-2064,2012
DOI: 10.1016/j.jacc.2012.01.045
[14] P. P. Toth, A. M. Patti, R. V. Giglio, et al., "Management of Statin Intolerance in 2018: Still More Questions Than Answers," American Journal of Cardiovascular Drugs, vol. 18, no. 3, pp. 157-173,2018
DOI: 10.1007/s40256-017-0259-7
[15] Jane Armitage. "The safety of statins in clinical practice," The Lancet, vol. 370, no. 9601, pp. 1781-1790,2007
DOI: 10.1016/S0140-6736(07)60716-8
[16] N. C. Ward, G. F. Watts, and R. H. Eckel. "Statin Toxicity," Circulation Research, vol. 124, no. 2, pp. 328-350,2019
DOI: 10.1161/CIRCRESAHA.118.312782
[17] P. D. Thompson, G. Panza, A. Zaleski, and B. Taylor. "Statin-Associated Side Effects," Journal of the American College of Cardiology, vol. 67, no. 20, pp. 2395-2410,2016
DOI: 10.1016/j.jacc.2016.02.071
[18] T. T. Sham, C. O. Chan, Y. H. Wang, J. M. Yang, D. K. Mok, and S. W. Chan. "A review on the traditional Chinese medicinal herbs and formulae with hypolipidemic effect," Biomed Res Int, vol. 2014, pp. 925302,2014
DOI: 10.1155/2014/925302
[19] J. O. Hendrickx, J. van Gastel, H. Leysen, B. Martin, and S. Maudsley. "High-dimensionality Data Analysis of Pharmacological Systems Associated with Complex Diseases," Pharmacological Reviews, vol. 72, no. 1, pp. 191-217,2020
DOI: 10.1124/pr.119.017921
[20] M. Yang, J. L. Chen, L. W. Xu, and G. Ji. "Navigating traditional chinese medicine network pharmacology and computational tools," Evidence-Based Complementary and Alternative Medicine, vol. 2013, pp. 731969,2013
DOI: 10.1155/2013/731969
[21] H. Ma, Y. Hu, Z. Zou, M. Feng, X. Ye, and X. Li. "Antihyperglycemia and Antihyperlipidemia Effect of Protoberberine Alkaloids From Rhizoma Coptidis in HepG2 Cell and Diabetic KK-Ay Mice," Drug Development Research, vol. 77, no. 4, pp. 163-170,2016
DOI: 10.1002/ddr.21302
[22] N. Ning, K. He, Y. Wang, et al., "Hypolipidemic Effect and Mechanism of Palmatine from Coptis chinensis in Hamsters Fed High-Fat diet," Phytotherapy Research, vol. 29, no. 5, pp. 668-673,2015
DOI: 10.1002/ptr.5295
[23] C. Y. Kim, K. S. Chung, S. Y. Cheon, et al., "Hypolipidemic effects of HVC1 in a high cholesterol dietinduced rat model of hyperlipidemia," Mol Med Rep, vol. 14, no. 4, pp. 3152-3158,2016
DOI: 10.3892/mmr.2016.5615
[24] A. M. Badawy, R. N. El-Naga, A. M. Gad, M. G. Tadros, and H. M. Fawzy. "Wogonin pre-treatment attenuates cisplatin-induced nephrotoxicity in rats: Impact on PPAR-gamma, inflammation, apoptosis and Wnt/beta-catenin pathway," Chemico-Biological Interactions, vol. 308, pp. 137-146,2019
DOI: 10.1016/j.cbi.2019.05.029
[25] D. S. Gelinas and J. McLaurin. "PPAR-alpha expression inversely correlates with inflammatory cytokines IL-1beta and TNF-alpha in aging rats," Neurochemical Research, vol. 30, no. 11, pp. 1369-1375,2005
DOI: 10.1007/s11064-005-8341-y
[26] H. D. Li, X. Chen, Y. Yang, et al., "Wogonin attenuates inflammation by activating PPAR-gamma in alcoholic liver disease," International Immunopharmacology, vol. 50, pp. 95-106,2017
DOI: 10.1016/j.intimp.2017.06.013
[27] R. J. Choi, J. Chun, S. Khan, and Y. S. Kim. "Desoxyrhapontigenin, a potent anti-inflammatory phytochemical, inhibits LPS-induced inflammatory responses via suppressing NF-kappaB and MAPK pathways in RAW 264.7 cells," International Immunopharmacology, vol. 18, no. 1, pp. 182-190,2014
DOI: 10.1016/j.intimp.2013.11.022
[28] S. Xiao, Z. Zhang, M. Chen, et al., "Xiexin Tang ameliorates dyslipidemia in high-fat diet-induced obese rats via elevating gut microbiota-derived short chain fatty acids production and adjusting energy metabolism," Journal of Ethnopharmacology, vol. 241, pp. 112032,2019
DOI: 10.1016/j.jep.2019.112032
[29] Christian Grommes, Gary E. Landreth, and Michael T. Heneka. "Antineoplastic effects of peroxisome proliferatoractivated receptor γ agonists," The Lancet Oncology, vol. 5, no. 7, pp. 419-429,2004
DOI: 10.1016/S1470-2045(04)01509-8
[30] T. Yamauchi, J. Kamon, H. Waki, et al., "The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance," Journal of Biological Chemistry, vol. 276, no. 44, pp. 41245-41254,2001
DOI: 10.1074/jbc.M103241200
[31] T. Goto. "A review of the studies on food-derived factors which regulate energy metabolism via the modulation of lipid-sensing nuclear receptors," Bioscience, Biotechnology, and Biochemistry, vol. 83, no. 4, pp. 579-588,2019
DOI: 10.1080/09168451.2018.1559025
[32] X. Palomer, E. Barroso, M. Zarei, G. Botteri, and M. Vazquez-Carrera. "PPARbeta/delta and lipid metabolism in the heart," Biochim Biophys Acta, vol. 1861, no. 10, pp. 1569-1578,2016
DOI: 10.1016/j.bbalip.2016.01.019
[33] J. Zheng, X. Xiao, Q. Zhang, M. Yu, J. Xu, and Z. Wang. "Maternal high-fat diet modulates hepatic glucose, lipid homeostasis and gene expression in the PPAR pathway in the early life of offspring," International Journal of Molecular Sciences, vol. 15, no. 9, pp. 14967-14983,2014
DOI: 10.3390/ijms150914967
[34] M. C. Zhou, P. Yu, Q. Sun, and Y. X. Li. "Expression profiling analysis: Uncoupling protein 2 deficiency improves hepatic glucose, lipid profiles and insulin sensitivity in high-fat diet-fed mice by modulating expression of genes in peroxisome proliferator-activated receptor signaling pathway," J Diabetes Investig, vol. 7, no. 2, pp. 179-189,2016
DOI: 10.1111/jdi.12402
[35] L. Pan, Y. Tian, H. Sun, Y. Wang, and G. Liu. "TMT-based proteomics analysis reveals the efficacy of jiangzhuo formula in improving the lipid profiles of dyslipidemia rats," Journal of Ethnopharmacology, vol. 264, pp. 113390,2021
DOI: 10.1016/j.jep.2020.113390
[36] M. Endres, P. U. Heuschmann, U. Laufs, and A. M. Hakim. "Primary prevention of stroke: blood pressure, lipids, and heart failure," European Heart Journal, vol. 32, no. 5, pp. 545-552,2011
DOI: 10.1093/eurheartj/ehq472
[37] M. M. Perez, L. M. S. Martins, M. S. Dias, et al., "Interleukin-17/interleukin-17 receptor axis elicits intestinal neutrophil migration, restrains gut dysbiosis and lipopolysaccharide translocation in high-fat diet-induced metabolic syndrome model," Immunology, vol. 156, no. 4, pp. 339-355,2019
DOI: 10.1111/imm.13028
[38] M. L. Matey-Hernandez, F. M. K. Williams, T. Potter, A. M. Valdes, T. D. Spector, and C. Menni. "Genetic and microbiome influence on lipid metabolism and dyslipidemia," Physiological Genomics, vol. 50, no. 2, pp. 117-126,2018
DOI: 10.1152/physiolgenomics.00053.2017
[39] X. Wang, R. Ilarraza, B. P. Tancowny, S. B. Alam, and M. Kulka. "Disrupted Lipid Raft Shuttling of FcepsilonRI by n-3 Polyunsaturated Fatty Acid Is Associated With Ligation of G Protein-Coupled Receptor 120 (GPR120) in Human Mast Cell Line LAD2," Front Nutr, vol. 7, pp. 597809,2020
DOI: 10.3389/fnut.2020.597809
[40] S. Manti, S. Leonardi, I. Panasiti, T. Arrigo, C. Salpietro, and C. Cuppari. "Serum IL-10, IL-17 and IL-23 levels as "bioumoral bridges" between dyslipidemia and atopy," Cytokine, vol. 99, pp. 43-49,2017
DOI: 10.1016/j.cyto.2017.07.002

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