基于网络药理学探究蒲参胶囊治疗高脂血症的作用机制
Study on Mechanism of Pushen Capsule for Treating Hyperlipidemia Based on Network Pharmacology
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摘要: 目的 基于网络药理学方法,构建蒲参胶囊药效物质靶点网络,分析其功效物质基础和作用靶标,阐述其治疗高脂血症的可能分子机制,为蒲参胶囊抗高脂血症的实验研究提供思路。方法 首先基于Arrowsmith非文献预测工具探讨蒲参胶囊各味中药及其组分和高脂血症的相关性。其次运用中药成分数据库联合Percepta平台ADME/T预测功能筛选蒲参胶囊药效活性成分,于Similarity Ensemble Approach,STITCH和Benchmark Database分子靶点网站确定活性成分作用靶点。接着使用GeneCards搜索高脂血症相关疾病靶点,联合活性化合物作用靶点,确定药物作用与高脂血症的共同潜在靶标,并使用Cytoscape将结果可视化展示,最后通过使用KEGG数据库及DAVID数据库进行靶标注释与分类。结果 通过Arrowsmith分析得出,蒲参胶囊各味中药药物作用靶点和高脂血症以及其相关疾病如“动脉粥样硬化”“糖尿病”等具有显著相关性,提示蒲参胶囊对这些疾病具有治疗作用。通过药理学方法筛选出活性成分共75个,主要作用靶标有261个,关键靶点和炎症反应相关。基于KEGG和DAVID数据库总结蒲参胶囊发挥活血化瘀,滋阴化浊的治疗作用主要可能是通过以下几条信号通路:①AGE-RAGE信号通路;②Malaria相关途径;③乙型肝炎相关途径;④VEGF信号通路;⑤肿瘤相关途径。结论 蒲参胶囊治疗高脂血症是通过多靶点、多通路共同作用,主要作用环节集中在抑制慢性炎症的发生发展。Abstract: OBJECTIVE Based on the network pharmacology technology, this research explores the medicinal substance basis and target of the Pushen capsule, and constructs a network of medicinal potential targets to explain the possible mechanism of the Pushen capsule in the treatment of hyperlipidemia, and provide research ideas for the pharmacodynamic basis of the Pushen capsule. METHODS Firstly, based on the Arrowsmith non-document prediction tool, the correlation between the Pushen capsule and its components and hyperlipidemia was discussed. Using the Chinese medicine ingredient database combined with the Percepta platform ADME/T predictive function to screen the active ingredients of the Pushen capsule, and determining the active ingredient target with the Similarity Ensemble Approach, STITCH and Benchmark Database molecular target sites. Applying GeneCards to search for hyperlipidemia-related disease targets, then combining active compound targets and identifying potential targets for drugs and hyperlipidemia, finally visualizing the results with cytoscape. Target annotation and classification can be made by using of the KEGG database and the DAVID database. RESULTS Through analyzing date of Arrowsmith, there was a significant correlation between the Pushen capsule and hyperlipidemia, as well as related diseases such as "atherosclerosis" and "diabetes", suggest that Pushen capsule has therapeutic effects on these diseases. A total of 75 active ingredients were screened by pharmacological methods, and the main target was 261 and Critical targets associated with inflammatory responses. Based on the KEGG and DAVID databases, the effect of Pushen capsule on improving blood circulation and removing phlegm was mainly through the following signal pathways: ①AGE-RAGE signaling pathway,②Malaria related pathway,③hepatitis B related pathway,④VEGF signaling pathway,⑤Cancer related pathway. CONCLUSION The treatment of hyperlipidemia with Pushen Capsule is through multiple targets and multiple pathways. The main effort is focused on reducing chronic inflammation.
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Key words:
- Pushen capsule /
- hyperlipidemia /
- disease-target network /
- network pharmacology /
- molecular mechanism
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[1] 刘晶,崔建华.高脂血症的中药治疗进展[J].天津药学,2017,29(3): 70-74. [2] 袁荣高,顾明华,古江勇.基于网络药理学研究大川芎方治疗偏头痛的作用机制[J].南京中医药大学学报,2016,32(6):571-576. [3] 马晓梅.蒲参胶囊对2型糖尿病血脂血糖的影响[J].中国临床药理学杂志,2013,29(12): 906-907,910. [4] 徐路.基于ARROWSMITH的医学非相关文献知识发现的方法探讨[J].科学技术创新,2018(2):111-113. [5] 曹美静,闫晨,郝丽娜.蒲参胶囊对大鼠心肌缺血再灌注损伤的保护作用[J].陕西医学杂志, 2018,47(7): 819-822. [6] 邵中兴, 顾宁.蒲参胶囊联合阿托伐他汀对冠心病合并血脂异常病人血脂水平的影响[J].中西医结合心脑血管病杂志, 2016, 14(3): 282-284. [7] 黄帅娟, 顾宁.中药治疗血脂异常的研究概况与展望[J].中医药导报, 2015, 21(20): 89-91. [8] LI J, ZHAO P, LI Y, et al. Systems pharmacology-based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease[J]. Sci Rep, 2015, 5: 15290. [9] WANG C, HU C, GAO D, et al. Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers[J]. Cancer Chemother Pharmacol, 2018,83(3):509-517. [10] SAHADE V, FRANCA S, BADARO R, et al. Obesity and postprandial lipemia in adolescents: risk factors for cardiovascular disease[J]. Endocrinol Nutr, 2012, 59(2): 131-139. [11] 田田,沈和荣.瑞舒伐他汀钙片与蒲参胶囊降脂疗效比较[J].临床医学研究与实践,2016, 1(19): 59-60. [12] 邵在宏.瑞舒伐他汀钙片与蒲参胶囊降脂疗效比较[J].现代中西医结合杂志,2014, 23(3): 259-261. [13] 邱宏涛,赵筱萍,李正,等.基于网络药理学的五味子木脂素类主要药效作用研究[J].中国中药杂志,2015,40(3): 522-527. [14] DLUDLA PV, NKAMBULE BB, JACK B, et al. Inflammation and oxidative stress in an obese state and the protective effects of gallic acid[J]. Nutrients, 2018, 11(1):1-8. [15] SYKES L, MACLNTYRE DA, TEOH TG, et al. Anti-inflammatory prostaglandins for the prevention of preterm labour[J]. Reproduction, 2014, 148(2): 29-40. [16] SEIJKENS T, KUSTERS P, ENGEL D, et al. CD40-CD40L: linking pancreatic, adipose tissue and vascular inflammation in type 2 diabetes and its complications[J]. Diab Vasc Dis Res, 2013, 10(2): 115-122. [17] CROFT M, BENEDICT CA, WARE CF. Clinical targeting of the TNF and TNFR superfamilies[J]. Nat Rev Drug Discov, 2013, 12(2): 147-168. [18] OLIVEIRA MC, MENEZES-GARCIA Z, HENRIQUES MC, et al. Acute and sustained inflammation and metabolic dysfunction induced by high refined carbohydrate-containing diet in mice[J]. Obesity, 2013, 21(9): 396-406. [19] ZHOU J, XU G, YAN J, et al. Rehmannia glutinosa (Gaertn.) DC. polysaccharide ameliorates hyperglycemia, hyperlipemia and vascular inflammation in streptozotocin-induced diabetic mice[J]. J Ethnopharmacol, 2015, 164: 229-238. [20] LABARRERE CA. Acute atherosis. A histopathological hallmark of immune aggression[J]. Placenta, 1988, 9(1): 95-108. [21] SPINELLA F, CAPRARA V, CIANFROCCA R, et al. The interplay between hypoxia, endothelial and melanoma cells regulates vascularization and cell motility through endothelin-1 and vascular endothelial growth factor[J]. Carcinogenesis, 2014, 35(4): 840-848. [22] 陈秋红,王晓勤,余满堂,等.血管活性物质对大鼠低氧性肺血管结构重建作用的研究[J].中国应用生理学杂志,2006,22(1):71-74. [23] ASHKENAZI A, FAIRBROTHER WJ, LEVERSON JD, et al. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors[J]. Nat Rev Drug Discov, 2017, 16(4): 273-284. [24] TSUJIMOTO Y, FINGER LR, YUNIS J, et al. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation[J]. Science, 1984, 226(4678): 1097-1099. [25] 郭艳,殷惠军,史大卓,等.心脑舒通胶囊对高脂血症大鼠心肌梗死后心肌细胞凋亡及Bax、Bcl-2蛋白表达的影响[J].中国中西医结合杂志,2006,26(6):541-544. [26] 刘永萍,杨如意.蒲参胶囊联合辛伐他汀对老年动脉粥样硬化患者临床疗效及血清VEGF、TGF-β1、TNF-α和IL-6水平的影响[J].中国地方病防治杂志,2018,33(6):685-688. [27] 张瑞斌,王淑芳,朱斌,等.蒲参胶囊对糖尿病大鼠肾脏PAI-1及MMP-9的影响[J].中国中西医结合肾病杂志,2012,13 (9):814-816. [28] GALKINA E, LEY K. Immune and inflammatory mechanisms of atherosclerosis[J]. Ann Rev Immunol, 2008,27(S1): 165-197. [29] BASTA G. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes[J]. Cardiovascul Res, 2004, 63(4):582-592.
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