IJCEMR
Based on Network Pharmacology and Molecular Docking Technology, the Mechanism of Folium Sennae, Aloe Combined with Panax Quinquefolium in Treating Functional Constipation Was Investigated
TOTAL VIEWS: 10237
Abstract
Objective: To explore the mechanism of folium sennae, aloe combined with panax quinquefolium in treating functional constipation (FC) based on network pharmacology and molecular docking method. Methods: Retrieval of all chemical components and action targets of folium sennae, aloe combined with panax quinquefolium using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (tcmsp). Relevant targets for functional constipation were accessed through Gencards, OMIM database, and first-line Western drug targets for the treatment of FC were searched through the drugbank database as a supplement. The STRING data platform was used to construct the interaction network of potential target proteins. Meanwhile, GO (gene ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) signaling pathway data were obtained, and the mechanism of action was analyzed and predicted. The PPI network topology was analyzed by Cytoscape 3.8.0 software, and the network diagram of “component-target-pathway” of FC in the three-drug combination treatment was constructed. Autodock Vina was used for molecular docking to further verify the accuracy of network pharmacological analysis of folium sennae, aloe combined with panax quinquefolium in the treatment of functional constipation. Results: The core active compounds of folium sennae, aloe combined with panax quinquefolium for the treatment of functional constipation are quercetin, kaempferol, β-Carotene and ginsenoside F2, and the core targets include PTGS2, MAPK1, Jun, VEGFA,IL6, etc. KEGG pathway enrichment analysis showed that the key targets of folium sennae, aloe combined with panax quinquefolium in the treatment of FC were mainly enriched in TNF signaling pathway, IL-17 signaling pathway, VEGF signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, etc. Molecular docking results verified that the average value of binding energy for each compound docking to the core target was less than -5kcal/mol with a good binding activity. Conclusion: This study preliminarily revealed the synergistic effect of panax quinquefolium combined with folium sennae and aloe in the treatment of functional constipation, and also showed that the combination use of three drugs have the characteristics of multi-component, multi-target, and multi pathway, which laid a foundation for further study of its mechanism of action.
References
[1] Wang Dongdong, Wu Xiangbai. (2019). Chinese Journal of General Practice, 2019, 22(24): 3016-3022.
[2] Aziz, I., Whitehead, W. E., Palsson, O. S., Törnblom, H., Simrén, M. (2020). An approach to the diagnosis and management of Rome IV functional disorders of chronic constipation. Expert Rev Gastroenterol Hepatol, 2020 Jan, 14(1): 39-46. doi: 10.1080/17474124.2020.1708718. Epub 2020 Jan 2. PMID: 31893959.
[3] Koppen, I. J. N., Vriesman, M. H., Saps, M., Rajindrajith, S., Shi, X., van Etten-Jamaludin, F. S., Di Lorenzo, C., Benninga, M. A., Tabbers, M. M. (2018). Prevalence of Functional Defecation Disorders in Children: A Systematic Review and Meta-Analysis. J Pediatr. , 2018 Jul, 198: 121-130. e6. doi: 10.1016/j.jpeds.2018.02.029. Epub 2018 Apr 12. PMID: 29656863.
[4] Suares, N. C., Ford, A. C. (2011). Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol, 2011Sep, 106(9): 1582-91; quiz1581, 1592. doi: 10.1038/ajg.2011.164. Epub 2011 May 24. PMID: 21606976.
[5] Tang Weifeng, Tang Xiaojun, Yang Wei. (2015). Research progress of Chinese and western medicine on functional constipation [J]. World Journal of Integrated Chinese and Western Medicine, 2015, 10(06): 880-884.
[6] Yuan Meng chun. Clinical research progress of functional constipation [J]. Inner Mongolia Journal of Traditional Chinese Medicine, 40(02): 140-143.
[7] Huang Suwei, Wang Chuijie. (2019). Journal of Liaoning University of Traditional Chinese Medicine, 2019, 21(01): 221-224.
[8] National Pharmacopoeia Commission. Chinese Pharmacopoeia [M]. Beijing: China Medical Science and Technology Press, 2020.
[9] Yue Wuyang, Peng Zihao, Chen Xuxi, Wu Rui, Chen Jinyao, Zhang Lishi. (2020). Effects of aloe vera, Panax quintillae and Senna leaf on intestinal and defecation function in mice [J]. Modern Preventive Medicine, 2020, 47(08): 1460-1463+1469.
[10] Chen Xuxi, Li Na, Yue Wuyang, Peng Zihao, Wu Rui, Chen Jinyao, Zhang Lishi. (2020). Effects of aloe vera, American ginseng and senna leaf on intestinal microflora in mice with constipation [J]. Modern Preventive Medicine, 2020, 47(24): 4497-4502+4506.
[11] Liu Jiahui, Lu Dongyong, Zhou Houming, Kuang Weihong, Chen Zexiong, Zhang Shijun. (2020). Chinese Journal of Traditional Chinese Medicine, 2020, 45(01): 163-168. (in Chinese)
[12] Liang Hong-bao, Li Rui, Yao Jing-chun, Qin Guo-fei, Zhang Hao, Zhang Gui-min. Study on the mechanism of Action of Shouhui Tongfu Capsule in treating constipation based on network pharmacology and molecular docking method [J]. Chinese Journal of Traditional Chinese Medicine, 46(03): 511-519.
[13] Jinlong Ru, Peng Li, JinanWang, Wei Zhou, Bohui Li, Chao Huang, Pidong Li, Zihu Guo, Weiyang Tao, Yinfeng Yang, Xue Xu, Yan Li, Yonghua Wang, Ling Yang. (2014). TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminformatics, 2014 Apr 16, 6(1): 13.
[14] Kim, S., Chen, J., Cheng, T., et al. (2021). PubChem in 2021: new data content and improved web interfaces. Nucleic Acids Res., 2021, 49(D1): D1388-D1395. doi:10.1093/nar/gkaa971.
[15] The UniProt Consortium, UniProt: the universal protein knowledgebase in 2021, Nucleic Acids Research, Volume 49, Issue D1, 8 January 2021, pp. D480-D48.
[16] Wishart, D. S., Feunang, Y. D., Guo, A. C., Lo, E. J., Marcu, A., Grant, J. R., Sajed, T., Johnson, D., Li, C., Sayeeda, Z., Assempour, N., Iynkkaran, I., Liu, Y., Maciejewski, A., Gale, N., Wilson, A., Chin, L., Cummings, R., Le, D., Pon, A., Knox, C., Wilson, M. (2017). DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res., 2017 Nov 8. doi: 10.1093/nar/gkx1037.
[17] Oliveros, J. C. (2007-2015). Venny. An interactive tool for comparing lists with Venn’s diagrams.
[18] STRINGv 11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res., 2019 Jan, 47: D607-613.
[19] Zhou, Y., Zhou, B., Pache, L., Chang, M., Khodabakhshi, A. H., Tanaseichuk, O., Benner, C., Chanda, S. K. (2019). Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun. , 2019 Apr 3, 10(1): 1523. doi: 10.1038/s41467-019-09234-6. PMID: 30944313; PMCID: PMC6447622.
[20] Heatmap was plotted by an online platform for data analysis and visualization. http://www.bioinformatics.com.cn.
[21] O. Trott, A. J. Olson. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry, 31(2010), 455-461.
[22] The PyMOL Molecular Graphics System, Version 2.4.0 Schrödinger, LLC.
[23] Xu Jiahui, Chen Qingguang, Zhang Liqiong, Han Xu, Liu Yahua, Jin Shenyi, Cai Mengjie, Liu Yuying, Lu Hao. Study on the mechanism of astragalus membranaceus in the treatment of Hashimoto’s thyroiditis based on network pharmacology and mo-lecular docking method [J]. Shanghai Journal of Traditional Chinese Medicine, 55(04): 6-14.
[24] Xu, Z. Y. (2020). Experimental study on regulating intestinal flora and improving slow transit constipation by Yangyin Yiqi Runchang Recipe [D]. Yunnan University of Chinese Medicine, 2020.
[25] Zou Xian-gang, Fu Shu-jie, Huang Xing-zhen, Wu Ling-ling, Jiang Wei-zhe. (2014). Study on the effect of shijiejiangzhi capsule on moistening intestine and relieving constipation [J]. Shizhen National Medicine and National Medicine, 2014, 25(01): 65-68.
[26] Dimidi, E., Christodoulides, S., Scott, S. M., Whelan, K. (2017). Mechanisms of Action of Probiotics and the Gastrointestinal Microbiota on Gut Motility and Constipation. Adv Nutr., 2017 May 15, 8(3): 484-494. doi:10.3945/an.116.014407. PMID:28507013; PMCID: PMC5421123.
[27] Zhang, J. W. (2014). Study on the purgative mechanism of quercetin and optimization of extraction process of quercetin from pine needles [D]. Guangzhou Medical University, 2014.
[28] Aa, L. X., Fei, F., Qi, Q., Sun, R. B., Gu, S. H., Di, Z. Z., Aa, J. Y., Wang, G. J., Liu, C. X. (2020). Rebalancing of the gut flora and microbial metabolism is responsible for the anti-arthritis effect of kaempferol. Acta Pharmacol Sin., 2020 Jan, 41(1): 73-81. doi: 10.1038/s41401-019-0279-8. Epub 2019 Aug 19. PMID: 31427695; PMCID: PMC7468310.
[29] Krinsky, N. I., Johnsone, J. (2005). Carotenoid actions and their relation to health and disease [J]. Molecular Aspects of Medicine, 2005, 26(6): 459-516.
[30] Cantorna, M. T., Snyder, L., Arora, J. (2019). Vitamin A and vitamin D regulate the microbial complexity, barrier function, and the mucosal immune responses to ensure intestinal homeostasis. Crit Rev Biochem Mol Biol., 2019 Apr, 54(2): 184-192. doi: 10.1080/10409238.2019.1611734. Epub 2019 May 14. PMID: 31084433; PMCID: PMC6629036.
[31] Gao Xia, Geng Ting, Ma Yang, Li Yan-jing, Huang Wen-zhe, Wang Zhen-zhong, Xiao Wei. (2016). Chinese Journal of Traditional Chinese Medicine, 2016, 41(12): 2329-2338.
[32] Liu Yan-yan, Zhang Kai, Guan Jiawei, Cao Xue-jiao, Wu Da-chang. (2015). Effects of ginsenosides on intestinal microflora of BALB/c mice [J]. Advances in Modern Biomedicine, 2015, 15(06): 1041-1045.
[33] Smith, W. L., DeWitt, D. L., Garavito, R. M. (2000). Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem, 2000, 69: 145-82. doi: 10.1146/annurev.biochem.69.1.145. PMID: 10966456.
[34] Lin, Y. M., Sarna, S. K., Shi, X. Z. (2012). Prophylactic and therapeutic benefits of COX-2 inhibitor on motility dysfunction in bowel obstruction: roles of PGE₂ and EP receptors. Am J Physiol Gastrointest Liver Physiol, 2012 Jan 15, 302(2): G267-75. doi: 10.1152/ajpgi.00326.2011. Epub 2011 Oct 28. PMID: 22038825; PMCID: PMC3341114.
[35] Liang, Y. J., Yang, W. X. (2019). Kinesins in MAPK cascade: How kinesin motors are involved in the MAPK pathway? Gene, 2019 Feb 5, 684: 1-9. doi: 10.1016/j.gene.2018.10.042. Epub 2018 Oct 17. PMID: 30342167.
[36] Ma Xiaoyan, Shen Qi, Hua Ying, Xie Ailan, Zhu Xueqiong. (2013). The role of MAPK signaling pathway in regulating AQP3 expression in human amniotic epithelial cells by compound Salvia miltiorrhiza injection [J]. Chinese Journal of Integrated Traditional and Western Medicine, 2013, 33(06): 778-782.
[37] Yang Xiao. (2018). Study on the mechanism of Tongzhan Decoction in the treatment of slow transit constipation based on MAPK signaling pathway [D]. Nanjing University of Chinese Medicine, 2018.
[38] Papavassiliou, A. G., Musti, A. M. (2020). The Multifaceted Output of c-Jun Biological Activity: Focus at the Junction of CD8 T Cell Activation and Exhaustion. Cells, 2020 Nov 13, 9(11): 2470. doi:10.3390/cells9112470. PMID: 33202877; PMCID: PMC7697663.
[39] Li, B., Ding, Y., Cheng, X., Sheng, D., Xu, Z., Rong, Q., Wu, Y., Zhao, H., Ji, X., Zhang, Y. (2020). Polyethylene microplastics affect the distribution of gut microbiota and inflammation development in mice. Chemosphere, 2020 Apr, 244: 125492. doi: 10.1016/j.chemosphere.2019.125492. Epub 2019 Nov 27. PMID: 31809927.
[40] Frysz-Naglak, D., Fryc, B., Klimacka-Nawrot, E., Mazurek, U., Suchecka, W., Kajor, M., Kurek, J., Stadnicki, A. (2011). Expression, localization and systemic concentration of vascular endothelial growth factor (VEGF) and its receptors in patients with ulcerative colitis. Int Immunopharmacol, 2011 Feb, 11(2): 220-5. doi: 10.1016/j.intimp.2010.11.023. Epub 2010 Nov 27. PMID: 21115119.
[41] Hurst, R. J., De Caul, A., Little, M. C., Kagechika, H., Else, K. J. (2013). The retinoic acid receptor agonist Am80 increases mucosal inflammation in an IL-6 dependent manner during Trichuris muris infection. J Clin Immunol., 2013 Nov, 33(8): 1386-94. doi: 10.1007/s10875-013-9936-8. Epub 2013 Sep 15. PMID: 24036839; PMCID: PMC3825562.
[42] O'Malley, D., Dinan, T. G., Cryan, J. F. (2011). Altered expression and secretion of colonic interleukin-6 in a stress-sensitive animal model of brain-gut axis dysfunction. J Neuroimmunol, 2011 Jun, 235(1-2): 48-55. doi: 10.1016/j.jneuroim.2011.04.003. Epub 2011 May 11. PMID: 21565410.
[43] Zheng Hongqun, Shang Mingfeng, Shen Weidong. (2016). Effects of intraperitoneal injection of tumor necrosis factor α on intestinal Cajal mesenchymal cells in rats [J]. Journal of Harbin Medical University, 2016, 50(05): 393-396+402.
[44] Bernardini, N., Ippolito, C., Segnani, C., Mattii, L., Bassotti, G., Villanacci, V., Blandizzi, C., Dolfi, A. (2013). Histopathology in gastrointestinal neuromuscular diseases: methodological and ontological issues. Adv Anat Pathol, 2013 Jan, 20(1): 17-31. doi: 10.1097/PAP.0b013e31827b65c0. PMID: 23232568.
[45] Wan Ye-min, Zeng Li, Qian Hai-hua. (2019). Effect of Tongzhan Decoction on PKA/MPKA signaling pathway in colon tissue of STC rat model [J]. Chinese Journal of Experimental Formulae, 2019, 25(05): 135-142.
[46] Bader, A. G., Kang, S., Zhao, L., Vogt, P. K. (2005). Oncogenic PI3K deregulates transcription and translation. Nat Rev Cancer, 2005 Dec, 5(12): 921-9. doi: 10.1038/nrc1753. PMID: 16341083.
[47] Li, M. H. (2015). Role of PI3K/AKT/eNOS signaling pathway in slow transit constipation in rats [D]. North China University of Science and Technology, 2015.
[48] Jiang Zhichao, Daffodil. (2018). Journal of Guangxi University of Traditional Chinese Medicine, 2018, 21(01): 1-4. (in Chinese).
How to cite this paper
Based on Network Pharmacology and Molecular Docking Technology, the Mechanism of Folium Sennae, Aloe Combined with Panax Quinquefolium in Treating Functional Constipation Was Investigated
How to cite this paper: Yanrong Zhan, Yaping Cui, Yang Liu, Jiyun Wu, Yan Ou, Hua Jiang. (2021) Based on Network Pharmacology and Molecular Docking Technology, the Mechanism of Folium Sennae, Aloe Combined with Panax Quinquefolium in Treating Functional Constipation Was Investigated. International Journal of Clinical and Experimental Medicine Research, 5(4), 466-479.
DOI: http://dx.doi.org/10.26855/ijcemr.2021.10.008
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