基于网络药理学的苋参合剂抗运动性疲劳作用机制研究
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摘要
目的:运用网络药理学分析苋参合剂抗运动性疲劳的有效成分、作用靶点及通路,探讨其抗运动性疲劳的可能机制。方法:通过中药化学成分数据库及文献检索,获取苋参合剂的化学成分;并依据TCMSP数据库的口服生物利用度(Oral Bioavailability, OB)和类药性指数(Drug Likeindex, DL)筛选出主要有效活性成分。借助DRAR-CPI分子对接服务器得到有效活性成分的潜在作用靶点,并以DAVID数据库对进行生物学功能和KEGG通路进行分析,通过已知运动性疲劳相关因素与发生机制,筛选疲劳相关功能通路,并得出苋参合剂抗运动性疲劳相关靶点。利用Cytoscape软件构建苋参合剂的有效活性成分-靶点网络图。结果:本研究共筛选出苋参合剂有效成分15种,抗运动性疲劳靶点172个。并发现该方在能量物质代谢、类固醇激素调节及免疫相关共17个生物学过程及12个通路中显著富集。结论:初步探究了苋参合剂抗运动性疲劳作用的主要潜在靶点和相关通路,为进一步实验和临床研究揭示其作用机制奠定了基础。
Objective: To predict the active compounds and effective targets of Xianshen Formula(XSF) on exercise-induced fatigue(EIF) by network pharmacology and explore the potential mechanism. Methods: We searched the constituent of XSF by literature reviewing and databases searching on TCMSP, HIT, TCM Database@Taiwan and TCMID. And then we screened potential active compounds based on oral bioavailability(OB) and drug like index(DL) in TCMSP database. The potential targets of active compounds were explored based on DRAR-CPI docking server and we analyzed the biological function and KEGG pathway of all targets by DAVID database. The literature, monograph and books about ERF were reviewed to filter out biological function and KEGG pathway relating to EIF. Then we retrieved targets of EIF. Furtherly, we established the effective constituents-antitumor targets networks of XSF using Cytoscape software and perform the network topology. Results: A total of 15 active compounds, 172 anti-ERF targets were predicted, which mainly involved 17 GO biological function and 12 KEGG pathway covering the metabolism of energetic substance, the regulation of steroid hormone and immune function. Conclusion: This study preliminarily evidenced the main targets and related pathways about anti-ERF effects of XSF, and established a foundation for further experimental studies of confirmation.
Objective: To predict the active compounds and effective targets of Xianshen Formula(XSF) on exercise-induced fatigue(EIF) by network pharmacology and explore the potential mechanism. Methods: We searched the constituent of XSF by literature reviewing and databases searching on TCMSP, HIT, TCM Database@Taiwan and TCMID. And then we screened potential active compounds based on oral bioavailability(OB) and drug like index(DL) in TCMSP database. The potential targets of active compounds were explored based on DRAR-CPI docking server and we analyzed the biological function and KEGG pathway of all targets by DAVID database. The literature, monograph and books about ERF were reviewed to filter out biological function and KEGG pathway relating to EIF. Then we retrieved targets of EIF. Furtherly, we established the effective constituents-antitumor targets networks of XSF using Cytoscape software and perform the network topology. Results: A total of 15 active compounds, 172 anti-ERF targets were predicted, which mainly involved 17 GO biological function and 12 KEGG pathway covering the metabolism of energetic substance, the regulation of steroid hormone and immune function. Conclusion: This study preliminarily evidenced the main targets and related pathways about anti-ERF effects of XSF, and established a foundation for further experimental studies of confirmation.
引文
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[36] Yang JH, Han SJ, Ryu JH, et al. Ginsenoside Rh2 ameliorates scopolamine-induced learning deficit in mice[J]. Biol Pharm Bull, 2009,32:1710-1715.
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[2] 冯连世, 冯美云, 冯炜权. 优秀运动员身体机能评定方法[M]. 北京: 人民体育出版社, 2003.
[3] 梁薇, 文眸. 运动性疲劳的中医观[J]. 现代医药卫生, 2016,32:3802-3805.
[4] 刘鲲鹏, 房敏, 戴德纯, 等. 推拿干预慢性疲劳综合征患者骨骼肌中位频率的临床研究[J]. J Integr Med, 2011,9:1083-1087.
[5] 王天芳, 薛晓琳, 张雅静, 等. “消疲怡神”配方颗粒干预肝郁脾虚型疲劳性亚健康状态的前瞻性随机双盲安慰剂对照试验[J]. J Intgr Med, 2011,9:515-524.
[6] Walters JR. New advances in the molecular and cellular biology of the small intestine[J]. Curr Opin Gastroenterol, 2002,18:161-167.
[7] Xu X, Zhang W, Huang C, et al. A novel chemometric method for the prediction of human oral bioavailability[J]. Int J Mol Sci, 2012,13:6964-6982.
[8] Luo H, Chen J, Shi L, et al. DRAR-CPI: a server for identifying drug repositioning potential and adverse drug reactions via the chemical-protein interactome[J]. Nucleic Acids Res, 2011,39:W492-498.
[9] Pundir S, Magrane M, Martin MJ, et al. Searching and Navigating UniProt Databases[J]. Curr Protoc Bioinformatics, 2015,50:1-10.
[10] Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources[J]. Nat Protoc, 2009,4:44-57.
[11] Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks[J]. Genome Res, 2003,13:2498-2504.
[12] Assenov Y, Ramírez F, Schelhorn SE, et al. Computing topological parameters of biological networks[J]. Bioinformatics, 2008,24:282.
[13] 张蕴琨, 丁树哲. 运动生物化学(“十二五”普通高等教育本科国家级规划教材)[M]. 北京: 高等教育出版社, 2015.
[14] Zhong L, Zhao L, Yang F, et al. Evaluation of anti-fatigue property of the extruded product of cereal grains mixed with Cordyceps militaris on mice[J]. J Int Soc Sports Nutr, 2017,14:15.
[15] 熊正英. 运动自由基生物学研究[M]. 北京: 科学出版社, 2010.
[16] Thompson D, Williams C, Kingsley M, et al. Muscle soreness and damage parameters after prolonged intermittent shuttle-running following acute vitamin C supplementation[J]. Int J Sports Med, 2001,22:68-75.
[17] Da Silva DK, Jacinto JL, De Andrade WB, et al. Citrulline Malate Does Not Improve Muscle Recovery after Resistance Exercise in Untrained Young Adult Men[J]. Nutrients, 2017,9(1):131-134.
[18] 林文弢. 运动训练生化分析[M]. 台北: 中国文化大学出版社, 2000.
[19] Varanoske AN, Hoffman JR, Church DD, et al. Beta-Alanine supplementation elevates intramuscular carnosine content and attenuates fatigue in men and women similarly but does not change muscle l-histidine content[J]. Psychopharmacology (Berl), 2017,48:16-25.
[20] Jones RL, Barnett CT, Davidson J, et al. Beta-alanine supplementation improves in-vivo fresh and fatigued skeletal muscle relaxation speed[J]. Eur J Appl Physiol, 2017,117:867-879.
[21] Horvath DM, Murphy RM, Mollica JP, et al. The effect of taurine and beta-alanine supplementation on taurine transporter protein and fatigue resistance in skeletal muscle from mdx mice[J]. Amino Acids, 2016,48:2635-2645.
[22] Invernizzi PL, Limonta E, Riboli A, et al. Effects of Acute Carnosine and beta-Alanine on Isometric Force and Jumping Performance[J]. Int J Sports Physiol Perform, 2016,11:344-349.
[23] Bourdillon N, Yazdani S, Nilchian M, et al. Overload blunts baroreflex only in overreached athletes[M]. J Sci Med Sport, 2018.
[24] Taylor MK, Padilla GA, Hernandez LM. Anabolic hormone profiles in elite military men: Robust associations with age, stress, and fatigue[J]. Steroids, 2017,124:18-22.
[25] Grandys M, Majerczak J, Kulpa J, et al. The importance of the training-induced decrease in basal cortisol concentration in the improvement in muscular performance in humans[J]. Physiol Res, 2016,65:109-120.
[26] Wan JJ, Qin Z, Wang PY, et al. Muscle fatigue: general understanding and treatment[J]. Exp Mol Med, 2017,49:e384.
[27] Axelson HW, Melberg A, Ronquist G, et al. Microdialysis and electromyography of experimental muscle fatigue in healthy volunteers and patients with mitochondrial myopathy[J]. Muscle Nerve, 2002,26:520-526.
[28] Graham TE, Rush JW, Van Soeren MH. Caffeine and exercise: metabolism and performance[J]. Can J Appl Physiol, 1994,19:111-138.
[29] Nugraha B, Karst M, Engeli S, et al. Brain-derived neurotrophic factor and exercise in fibromyalgia syndrome patients: a mini review[J]. Rheumatol Int, 2012,32:2593-2599.
[30] Le Moine CM, Morash AJ, Mc Clelland GB. Changes in HIF-1alpha protein, pyruvate dehydrogenase phosphorylation, and activity with exercise in acute and chronic hypoxia[J]. Am J Physiol Regul Integr Comp Physiol, 2011,301:R1098-1104.
[31] Cadegiani FA, Kater CE. Growth hormone (GH) and prolactin responses to a non-exercise stress test in athletes with overtraining syndrome: results from the Endocrine and metabolic Responses on Overtraining Syndrome (EROS)-EROS-STRESS[M]. J Sci Med Sport, 2017.
[32] Daly W, Seegers CA, Rubin DA, et al. Relationship between stress hormones and testosterone with prolonged endurance exercise[J]. Eur J Appl Physiol, 2005,93:375-380.
[33] 封飞虎, 凌波. 运动生理学[M]. 武汉: 华中科技大学出版社, 2014.
[34] Nestora S, Merlier F, Prost E, et al. Solid-phase extraction of betanin and isobetanin from beetroot extracts using a dipicolinic acid molecularly imprinted polymer[J]. J Chromatogr A, 2016,1465:47-54.
[35] Dominguez R, Mate-Munoz JL, Cuenca E, et al. Effects of beetroot juice supplementation on intermittent high-intensity exercise efforts[J]. J Int Soc Sports Nutr, 2018,15:2.
[36] Yang JH, Han SJ, Ryu JH, et al. Ginsenoside Rh2 ameliorates scopolamine-induced learning deficit in mice[J]. Biol Pharm Bull, 2009,32:1710-1715.
[37] Fernandez ML, Vega-Lopez S. Efficacy and safety of sitosterol in the management of blood cholesterol levels[J]. Cardiovasc Drug Rev, 2005,23:57-70.
[38] Bouic PJ, Clark A, Lamprecht J, et al. The effects of B-sitosterol (BSS) and B-sitosterol glucoside (BSSG) mixture on selected immune parameters of marathon runners: inhibition of post marathon immune suppression and inflammation[J]. Int J Sports Med, 1999,20:258-262.