药学学报, 2018, 53(9): 1449-1457
引用本文:
衡霞, 朱宝杰, 孙莉敏, 潘林梅, 段金廒, 张启春, 朱华旭. 基于网络药理学的黄连解毒汤调节巨噬细胞炎症反应和代谢的作用机制研究[J]. 药学学报, 2018, 53(9): 1449-1457.
HENG Xia, ZHU Bao-jie, SUN Li-min, PAN Lin-mei, DUAN Jin-ao, ZHANG Qi-chun, ZHU Hua-xu. Network pharmacology-based study on mechanisms of Huanglian Jiedu Decoction impact on macrophage inflammation response[J]. Acta Pharmaceutica Sinica, 2018, 53(9): 1449-1457.

基于网络药理学的黄连解毒汤调节巨噬细胞炎症反应和代谢的作用机制研究
衡霞1,2, 朱宝杰1,2, 孙莉敏1,2, 潘林梅1,2, 段金廒1,2, 张启春1,2, 朱华旭1,2
1. 南京中医药大学 江苏省中药资源产业化过程协同创新中心, 江苏 南京 210023;
2. 南京中医药大学 江苏省方剂高技术研究重点实验室, 江苏 南京 210023
摘要:
运用网络药理学方法探究黄连解毒汤调节巨噬细胞炎症反应、糖酵解、鞘脂代谢和谷氨酰胺代谢等方面的多成分、多靶点、多通路的相互作用规律和调控网络,为创新药物研究奠定基础。通过TCMSP数据库筛选黄连解毒汤活性成分,PharmMapper数据库预测靶点蛋白,DAVID数据库进行通路注释和分析,Cytoscape 3.2.1软件构建“活性成分-靶点-通路”网络图,GENEMANIA数据库进行蛋白相互作用分析,Systems Dock Web Site数据库进行分子对接验证。预测结果表明,黄连解毒汤中共筛选出84个活性成分,作用靶点111个,其中与巨噬细胞炎症相关的靶点蛋白13个,涉及代谢通路14条;与糖酵解、鞘脂代谢、谷氨酰胺代谢相关的靶点蛋白34个,涉及代谢通路8条。炎症相关蛋白和代谢相关蛋白通过物理相关性、蛋白共表达等方式互相作用,小檗碱、黄芩苷和栀子苷与5个重要靶点均能较好结合。黄连解毒汤可能通过作用于糖酵解、鞘脂代谢和谷氨酰胺代谢的相关靶点,影响其代谢过程中的代谢产物和酶,从而调节巨噬细胞炎症反应。
关键词:    网络药理学      黄连解毒汤      炎症      代谢     
Network pharmacology-based study on mechanisms of Huanglian Jiedu Decoction impact on macrophage inflammation response
HENG Xia1,2, ZHU Bao-jie1,2, SUN Li-min1,2, PAN Lin-mei1,2, DUAN Jin-ao1,2, ZHANG Qi-chun1,2, ZHU Hua-xu1,2
1. Jiangsu Collaboration Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China;
2. Jiangsu Province Key Laboratory of High Technology Research, Nanjing University of Chinese Medicine, Nanjing 210023, China
Abstract:
This study was designed to explore the impact of Huanglian Jiedu Decoction (HLJDT) on macrophage inflammation reaction using the network pharmacology method. Glycolysis, sphingolipid metabolism and glutamine metabolism were also investigated for "multi-component, multi-target and multi-pathway", which supports a foundation for drug innovative research. The TCMSP database was used to screen the active components of HLJDT, the target protein predicted by PharmMapper database and the DAVID database for pathways annotation and analysis. The Cytoscape 3.2.1 software was used to construct the active componenttarget-pathway network map and GENEMANIA database for protein interaction analysis. System Dock Database Site is used in verification of molecular docking. The results showed that 84 active ingredients were screened in HLJDT with a total of 111 target targets. Fourteen pathways are affected according to 13 macrophage-related inflammatory proteins, and 8 pathways including 34 target proteins from glycolysis, sphingolipid metabolism and glutamine metabolism. Inflammation-related proteins and metabolism-related proteins can interact with each other through physical correlation, protein co-expression, etc. Berberine, baicalin and geniposide combined well with 5 important targets. Huanglian Jiedu Decoction may act on the glycolysis and sphingolipid pathways to regulate macrophage inflammatory responses.
Key words:    network pharmacology    Huanglian Jiedu Tang    inflammation    metabolism   
收稿日期: 2018-03-29
DOI: 10.16438/j.0513-4870.2018-0276
基金项目: 国家自然科学基金资助项目(81573635).
通讯作者: 张启春,Tel/Fax:86-25-85811509,E-mail:zhangqc@njucm.edu.cn;朱华旭,Tel/Fax:86-25-85811509,E-mail:huaxu72@126.com
Email: zhangqc@njucm.edu.cn;huaxu72@126.com
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参考文献:
[1] Liu AL, Du GH. Network pharmacology:new guidelines for drug discovery[J]. Acta Pharm Sin (药学学报), 2010, 45:1472-1477.
[2] Liu ZH, Sun XB. Network pharmacology:new opportunity for the modernization of traditional Chinese medicine[J]. Acta Pharm Sinica (药学学报), 2012, 47:696-703.
[3] Wang PR, Wang JS, Yang MH, et al. Neuroprotective effects of Huang-Lian-Jie-Du-Decoction on ischemic stroke rats revealed by H NMR metabolomics approach[J]. J Pharm Biomed Anal, 2014, 88:106-116.
[4] Hsu YL, Kuo PL, Tzeng TF, et al. Huang-lian-jie-du-tang, a traditional Chinese medicine prescription, induces cell-cycle arrest and apoptosis in human liver cancer cells in vitro and in vivo[J]. Gastroenterol Hepatol, 2008, 23:290-299.
[5] Zhang XJ, Deng YX, Shi QZ, et al. Hypolipidemic effect of the Chinese polyherbal Huanglian Jiedu decoction in type 2 diabetic rats and its possible mechanism[J]. Phytomedicine, 2014, 21:615-623.
[6] Hu Y, Hu Z, Wang S, et al. Protective effects of Huang-LianJie-Du-Tang and its component group on collagen-induced arthritis in rats[J]. Ethnopharmacol, 2013, 150:1137-1144.
[7] Sun LM, Liu LF, Zhu HX, et al. Network pharmacologybased study on intervention mechanism of Huanglian Jiedu decoction in the treatment of Alzheimer's disease[J]. Acta Pharm Sin (药学学报), 2017, 52:1268-1275.
[8] Hsin KY, Ghosh S, Kitano H. Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology[J]. PLoS One, 2013, 8:e83922.
[9] Qian ZL, Li H, Zhu HX, et al. Preliminary study on the correlation between pharmacokinetics and pharmacodynamics of index components in Huanglian Jiedu decoction[J]. Chin J Exp Form (中国实验方剂学杂志), 2011, 17:122-128.
[10] Xiao YL, Lu FE, Xu LJ, et al. Effect of Huanglian Jiedu decoction on vascular endothelial function in type 2 diabetic rats[J]. China J Chin Mater Med (中国中药杂志), 2005, 30:1767-1770.
[11] Ma YL, Wang BB, Han JY, et al. Effect of Huanglian Jiedu decoction on local and aortic vascular local immune response in high-fat diet ApoE-/- mice[J]. Chin J Integr Tradit Chin Western Med (中国中西医结合杂志), 2013, 33:1520-1525.
[12] Sun Y, Wang JP, Zhang YL, et al. The inhibitory effect of Huanglian Jiedu Tang on mouse S180 transplanted tumor[J]. J Northeast Agric Univ (东北农业大学学报), 2013, 44:63-67.
[13] Peng SL, Liu LF, Zhu HX, et al. Effects of combination drugs and Huanglian Jiedu decoction on the bioactivity of berberine in rat brain[J]. Chin Tradit Herb Drugs (中草药), 2016, 47:2877-2882.
[14] Ho YT, Yang JS, Li TC, et al. Berberine suppresses in vitro, migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-κB, u-PA and MMP-2 and -9[J]. Cancer Lett, 2009, 279:155-162.
[15] Bae DS, Kim YH, Pan CH, et al. Protopine reduces the inflammatory activity of lipopolysaccharide-stimulated murine macrophages[J]. BMB Rep, 2012, 45:108-113.
[16] Akhter MH, Sabir M, Bhide NK. Possible mechanism of antidiarrhoeal effect of berberine[J]. Indian J Med Res, 1979, 70:233-241.
[17] Guo C. Berberine Improves Insulin Resistance by Inhibiting Infiltration of Adipose Tissue Macrophages (小檗碱通过抑制脂肪组织巨噬细胞浸润改善胰岛素抵抗的研究)[D]. Nanjing:Nanjing Univ Chin Med, 2015.
[18] Curi TC, Melo MP, Azevedo RB, et al. Glutamine utilization by rat neutrophils:presence of phosphate dependent glutaminase[J]. Am J Physiol, 1997, 273:1124-1129.
[19] Yassad A, Lavoinne A, Bion A, et al. Glutamine accelerates IL-6 production by rat peritoneal macrophages in culture[J]. FEBS Lett, 1997, 413:81-84.
[20] Jin J. Analysis of Chemical Constituents of Huanglian Jiedu Decoction and Its Effect on Anti-hyperlipidemia (黄连解毒汤化学成分分析及其抗高脂血症作用的研究)[D]. Changchun:Jilin University, 2008.
[21] Liu Y, Lou SY, He YM, et al. Effects of berberine on the proliferation and differentiation-related genes PPAR γ C/EBPα mRNA and protein expression in 3T3-L1 preadipocytes[J]. Chin J Integr Tradit Chin Western Med (中国中西医结合杂志), 2008, 28:1005-1009.
[22] Piao CL, Yang SY, Tong XL, et al. Discussion on prevention and treatment of obesity type 2 diabetes by Chinese medicine from the mechanism of adipose tissue inflammation[J]. J Rehabil (康复学报), 2009, 19:61-63.
[23] He X, Huang Y, Li B, et al. Deregulation of sphingolipid metabolism in Alzheimer's disease[J]. Neurobiol Aging, 2010, 31:398-408.
[24] Gemma C, Smith MA, Samar B, et al. Increased isoprostane and prostaglandin are prominent in neurons in Alzheimer disease[J]. Mol Neurodegener, 2007, 2:2.
[25] Haughey NJ, Bandaru VV, Bae M, et al. Roles for dysfunctional sphingolipid metabolism in Alzheimer's disease neuropathogenesis[J]. Biochim Biophys Acta, 2010, 1801:878-886.
[26] Hannun YA, Obeid LM. The ceramide-centric universe of lipid-mediated cell regulation:stress encounters of the 1ipid kind[J]. J Biol Chem, 2002, 277:25847-25850.
[27] Nakao S, Moriyama S, Segawa M, et al. C-2-ceramide inhibits the prostaglandin E-2-induced accumulation of cAMP in human gingival fibroblasts[J]. Mol Cancer Ther, 2010, 9:1378-1395.
[28] Ballou LR, Laulederkind SJ, Rosloniec EF, et al. Ceramide signalling and the immune response[J]. Biochim Biophys Acta, 1996, 1301:273-287.
[29] Cutler RG, Kelly J, Storie K, et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease[J]. Proc Nat Acad Sci U S A, 2004, 101:2070-2075.
[30] Sun LM, Zhu BJ, Cao HT, et al. Explore the effects of Huang-Lian-Jie-Du-Tang on Alzheimer's disease by UPLCQTOF/MS-based plasma metabolomics study[J]. J Pharm Biomed Anal, 2017, 151:75-83.
[31] Sun GL, Sun W, Lan Q, et al. The sphingomyelin metabolism of cerebral ischemia[J]. Prog Mod Biomed (现代生物医学进展), 2015, 15:1566-1569.
[32] Zhang QC, Bian HM, Guo LW, et al. Berberine preconditioning protects neurons against ischemia via sphingosine-1-phosphate and hypoxia-inducible factor-1α[J]. Am J Chin Med, 2016, 44:927-941.
[33] Murphy CJ, Newsholme P. Importance of glutamine metabolism in murine macrophages and human monocytes to L-arginine biosynthesis and rates of nitrite or urea production[J]. Clin Sci, 1998, 95:397-407.
[34] Ziegler TR, Daignault NM. Glutamine regulation of human immune cell function[J]. Nutrition, 2000, 16:458-459.
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