Mechanism of Action of Trichosanthis Fructus-Allii Macrostemonis Bulbus Herb Pairs Against Hyperlipidemia Based on Network Pharmacology

Hua ZHONG; Jing-wen QIU; Hong-fei WU; He XU; Peng ZHANG; Cheng-jiao XUE; Peng-cheng JIA

doi:10.13422/j.cnki.syfjx.20201603

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Mechanism of Action of Trichosanthis Fructus-Allii Macrostemonis Bulbus Herb Pairs Against Hyperlipidemia Based on Network Pharmacology

Data Mining | 更新时间：2020-09-09

- Mechanism of Action of Trichosanthis Fructus-Allii Macrostemonis Bulbus Herb Pairs Against Hyperlipidemia Based on Network Pharmacology
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 18, Pages: 154-165(2020)
- 作者机构：
  
  安徽中医药大学药学院，合肥230000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20201603
  CLC： R2-0;R22;R285.5
- Received：17 December 2019，
  
  Published Online：09 June 2020，
  
  Published：20 September 2020
- 稿件说明：
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钟华,仇静文,吴鸿飞等.基于网络药理学研究瓜蒌-薤白药对抗高脂血症作用机制[J].中国实验方剂学杂志,2020,26(18):154-165.

ZHONG Hua,QIU Jing-wen,WU Hong-fei,et al.Mechanism of Action of Trichosanthis Fructus-Allii Macrostemonis Bulbus Herb Pairs Against Hyperlipidemia Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(18):154-165.
钟华,仇静文,吴鸿飞等.基于网络药理学研究瓜蒌-薤白药对抗高脂血症作用机制[J].中国实验方剂学杂志,2020,26(18):154-165. DOI： 10.13422/j.cnki.syfjx.20201603.

ZHONG Hua,QIU Jing-wen,WU Hong-fei,et al.Mechanism of Action of Trichosanthis Fructus-Allii Macrostemonis Bulbus Herb Pairs Against Hyperlipidemia Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(18):154-165. DOI： 10.13422/j.cnki.syfjx.20201603.

摘要

目的

基于高脂血症大鼠模型和网络药理学技术分析瓜蒌-薤白药对抗高脂血症的作用机制。

方法

通过瓜蒌-薤白药对低、中、高剂量（1，2，4 g·kg

-1

·d

-1

）预防性给药高脂血症大鼠，检测血脂和炎症因子水平。采用中药系统药理学数据库和分析平台（TCMSP）和文本挖掘筛选瓜蒌-薤白药对活性成分，Swiss Target Prediction，Similarity ensemble approach（SEA），DrugBank数据库筛选与活性成分对应的作用靶点；通过Therapeutic Target Database（TTD），Online Mendelian Inheritance in Man（OMIM），DrugBank和DisGeNET数据库收集疾病靶点。整合交集活性成分的作用靶点和疾病靶点，并通过拓扑学参数筛选，获得瓜蒌-薤白药对抗高脂血症的主要候选靶点。通过ClueGO进行京都基因与基因组百科全书（KEGG）通路富集，the Database for Annotation，Visualization and Integrated Discovery（DAVID）数据库进行基因本体（GO）功能富集分析。通过Cytoscape构建中药-成分-靶点网络模型、靶点-通路网络模型，并分析其串扰靶点和信号通路。

结果

动物实验表明，瓜蒌-薤白药对预防性给药可明显降低高脂血症大鼠血清中总胆固醇（TC），甘油三酯（TG），低密度脂蛋白胆固醇（LDL-C）水平，升高高密度脂蛋白胆固醇（HDL-C）水平，抑制白细胞介素-6（IL-6），肿瘤坏死因子-

（TNF-

）表达（

0.05，

0.01）。亚油酸乙酯，香叶木素，

-菠菜甾醇等27个活性成分可能是“瓜蒌-薤白”药对主要药效成分，16个串扰靶点和10条信号通路可能是其主要药效靶点和通路；药对主要靶向载脂蛋白A1（APOA1），载脂蛋白A2（APOA2），载脂蛋白C3（APOC3），脂蛋白脂肪酶（LPL），低密度脂蛋白受体（LDLR）等串扰靶点影响胆固醇代谢、胆汁分泌、过氧化物酶体增殖物激活型受体（PPAR）信号通路调节脂质水平；靶向肿瘤坏死因子（TNF），IL-6，IL-1B，丝裂原活化蛋白激酶1（MAPK1），C-C基序趋化因子2（CCL2）等串扰靶点影响TNF信号通路，Toll样受体信号通路，白细胞介素-17（IL-17）信号通路，缺氧诱导因子（HIF）信号通路调节炎症因子水平。DAVID数据库进行GO富集分析，表明药对主要通过炎症反应、脂质定位、储存和脂质代谢等生物学过程治疗高脂血症。

结论

通过这些发现可预测瓜蒌-薤白药对干扰高脂血症的作用机制，为瓜蒌-薤白药对的物质基础和临床应用提供理论基础。

Abstract

Objective

Based on the hyperlipidemia rat model and network pharmacology technology

the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia was analyzed.

Method

The levels of blood lipids and inflammatory factors were measured through prophylactic administration of low

medium and high-dose Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs in hyperlipidemia rats. The active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs were screened out through Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and text mining. The targets of active ingredients screened through the Swiss Target Prediction

Similarity ensemble approach (SEA)

DrugBank database. The disease targets were collected through Therapeutic Target Database (TTD)

Online Mendelian Inheritance in Man (OMIM)

DrugBank

DisGeNET database. The targets of active ingredients and disease target were integrated

and screened through topological parameters to gain the main candidate targets of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and the gene ontology (GO) functional enrichment analysis were conducted through ClueGO and Database for Annotation

Visualization and Integrated Discovery (DAVID)

respectively. The traditional Chinese medicine-chemical ingredient-target network model

and the target-pathway network model were constructed through Cytoscape

and their crosstalk target and signal pathway were analyzed.

Result

Animal experiments showed that the prophylactic administration of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs significantly reduced the levels of total cholesterol (TC)

triglycerides (TG)

low-density lipoprotein cholesterol (LDL-C) in serum of rats with hyperlipidemia

increased high-density lipoprotein (HDL-C) levels

and inhibited the expressions of interleukin-6 (IL-6) and tumor necrosis factor-

(TNF-

). According to the findings

27 active ingredients

such as mandenol

diosmetin and

-spinasterol

might be the main active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs

16 crosstalk targets and 10 signal pathways might be the main therapeutic targets and pathways

main targeting apolipoprotein A1 (APOA1)

apolipoprotein A2 (APOA2)

apolipoprotein C3 (APOC3)

lipoprotein lipase (LPL)

low-density lipoprotein receptor (LDLR) and other crosstalk targets affected cholesterol metabolism

bile secretion

peroxisome proliferator activated receptor (PPAR) signaling pathway in regulating the lipid level

targeting tumor necrosis factor (TNF)

IL-6

interleukin-1

(IL-1

)

mitogen-activated protein kinase 1 (MAPK1)

C-C motif chemokine 2 (CCL2) and other crosstalk targets affected tumor necrosis factor (TNF) signaling pathway

Toll-like receptor signaling pathway

interleukin-17 (IL-17) signaling pathway

and hypoxia inducible factor (HIF) signaling pathway in regulating the inflammatory factor level. The DAVID database for GO enrichment analysis showed that the hyperlipidemia was treated mainly through biological processes

such as inflammation

lipid localization

storage and lipid metabolism.

Conclusion

These findings can predict the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia

and provide a theoretical basis for the material basis and clinical application of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs.

关键词

Keywords

references

梁伟 , 何家振 , 韩林涛 , 等 . 瓜蒌-薤白药对治疗胸痹作用机制的研究 [J]. 时珍国医国药 , 2015 , 26 ( 2 ): 414 - 416 .

张仲景 . 金匮要略方略 [M]. 北京 : 人民卫生出版社 , 1978 : 27 - 28 ．

张沛然，郭改会 . 高脂血症的发病机制及分类 [J]. 中国临床医生 , 2012 , 40 ( 3 ): 18 - 20 .

AL-TAMIMI H , AL-DAWOOD A , AWAISHESH S . Resveratrol mitigates hypercholesterolemia exacerbated hyperthermia in chronically heat-stressed rats [J]. Vet World , 2019 , 12 ( 2 ): 337 - 344 .

王宏 , 江茜 , 康利 , 等 . 基于微生物16S rDNA测序技术研究高脂血症豚鼠肠道菌群的变化 [J]. 中国动脉硬化杂志 , 2018 , 26 ( 10 ): 1011 - 1015 .

ZHANG H M , TANG D L , TONG L , et al . Gualou xiebai banxia decoction inhibits NF-kappa B-dependent inflammation in myocardial ischemia-reperfusion injury in rats [J]. J Tradit Chin Med , 2011 , 31 ( 4 ): 338 - 343 .

ZHANG B Y , ZHENG Y F , PANG X C , et al . Network Pharmacology-based Study of the Active Constituenof Chinese Medicinal Formulae for Antitumor Mechanism [J]. World J Tradit Chin Med , 2018 , 4 ( 2 ): 43 - 53 .

李梢，张博 . 中药网络药理学：理论、方法与应用 [J]. 中国天然药物 , 2013 , 11 ( 2 ): 110 - 120 .

ZHENG J , WU M , WANG H , et al . Network pharmacology to unveil the biological basis of health-strengthening herbal medicine in cancer treatment [J]. Cancers , 2018 , 10 ( 11 ): 461 - 484 .

赵帅 , 吴东雪 , 陈茜 , 等 . 基于网络药理学的豨莶草治疗缺血性脑卒中作用机制研究 [J]. 中国中药杂志 , 2019 , 44 ( 13 ): 2727 - 2735 .

蒋跃平 , 陈章义 , 莫芳 , 等 . 基于网络药理学的莲子心中生物碱类成分发挥传统安神功效的药理机制研究 [J]. 中国中药杂志 , 2019 , 44 ( 19 ): 4225 - 4233 .

DING Y F , PENG Y R , LI J , et al . Gualou Xiebai Decoction prevents myocardial fibrosis by blocking TGF-beta/Smad signalling [J]. J Pharm Pharmacol , 2013 , 65 ( 9 ): 1373 - 1381 .

焦宏 , 马建伟 , 陈彦静 , 等 . 桂枝汤对高脂血症心肌缺血大鼠炎性细胞因子的影响 [J]. 中国中药杂志 , 2012 , 37 ( 11 ): 1634 - 1637 .

LI T B , ZHANG J J , LIU B , et al . Dysfunction of endothelial progenitor cells in hyperlipidemic rats involves the increase of NADPH oxidase derived reactive oxygen species production [J]. Can J Physiol Pharmacol , 2017 , 95 ( 5 ): 474 - 480 .

YAN L L , ZHANG W Y , WEI X H , et al . Gualou Xiebai decoction,a traditional Chinese medicine,prevents cardiac reperfusion injury of hyperlipidemia rat via energy modulation [J]. Front Physicol , 2018 , 9 : 296 - 311 .

YUE S J , LIU J , FENG W W , et al . System pharmacology-based dissection of the synergistic mechanism of Huangqi and Huanglian for diabetes mellitus [J]. Front Pharmacol , 2019 , 8 : 694 - 711 .

LI F , DUAN J , ZHAO M , et al . A network pharmacology approach to reveal the protective mechanism of Salvia miltiorrhiza-Dalbergia odorifera coupled-herbs on coronary heart disease [J]. Sci Rep-Uk , 2019 , 9 ( 1 ): 19343 - 19354 .

ZHAO J , LV C , WU Q , et al . Computational systems pharmacology reveals an antiplatelet and neuroprotective mechanism of Deng-Zhan-Xi-Xin injection in the treatment of ischemic stroke [J]. Pharmacol Res , 2019 , 147 : 104365-104413 .

CHEN Z , WANG X , LI Y , et al . Comparative network pharmacology analysis of classical TCM prescriptions for chronic liver disease [J]. Front Pharmacol , 2019 , 10 : 1353 - 1400 .

HAO D , DANBIN W , MAOJUAN G , et al . Ethanol extracts of Danlou tablet attenuate atherosclerosis via inhibiting inflammation and promoting lipid effluent [J]. Pharmacol Res , 2019 , 146 : 104306-104330 .

阮美丹 , 曾祥法 , 韩林涛 , 等 . 液质法测定瓜蒌-薤白药对活性成分槲皮素的含量 [J]. 湖北中医药大学学报 , 2018 , 20 ( 5 ): 36 - 38 .

LI C , ZHANG W Y , YU Y , et al . Discovery of the mechanisms and major bioactive compounds responsible for the protective effects of Gualou Xiebai Decoction on coronary heart disease by network pharmacology analysis [J]. Phytomedicine , 2019 , 56 : 261 - 268 .

孙晓业，吴红华，张鹏 . 瓜蒌薤白类方的化学成分及药理活性研究进展 [J]. 中国药房 , 2013 , 24 ( 11 ): 1044 - 1046 .

滕勇荣，张永清 . 瓜蒌化学成分研究进展 [J]. 山东中医药大学学报 , 2011 , 35 ( 1 ): 85 - 86 .

YANG Z , LIU G , YIN J , et al . The fucoidan A2 from the brown seaweed Ascophyllum nodosum lowers lipid by improving reverse cholesterol transport in C57BL/6J mice fed a high-fat diet [J]. J Agr Food Chem , 2019 , 67 ( 20 ): 5782 - 5791 .

陈国良，刘立伟，谢爽 , 等 . 高密度脂蛋白胆固醇代谢及其对冠心病影响的研究进展 [J]. 心血管病学进展 , 2010 , 31 ( 3 ): 360 - 363 .

吴建良 , 郝聪俐 , 宋晓华 , 等 . 药用亚油酸乙酯的研制 [J]. 浙江化工 , 2004 , 35 ( 5 ): 5 - 14 .

万丽娟 , 卢金清 , 许俊洁 , 等 . 瓜蒌子化学成分和药理作用的研究进展 [J]. 中国药房 , 2015 , 26 ( 31 ): 4440 - 4443 .

周重楚 , 孙晓波 , 刘建勇 , 等 . α -菠菜甾醇的抗炎作用 [J]. 药学学报 , 1985 , 20 ( 4 ): 257 - 261 .

杨蕾磊 , 陈科力 . 香叶木素的检测方法与生物活性及其机制研究进展 [J]. 中国药房 , 2017 , 28 ( 10 ): 1426 - 1429 .

王毅 . 羟基芫花素配伍芹菜素体外协同抗胶质瘤作用及其机制研究 [D]. 大连 : 大连医科大学 , 2014 : 1 - 44 .

白庆云 , 梁辉 , 袁功文 , 等 . 香叶木素-7- O - β - D -葡萄糖苷的抗炎作用研究 [J]. 药学学报 , 2015 , 37 ( 12 ): 15 - 17 .

刘金娜 , 温春秀 , 刘铭 , 等 . 瓜蒌的化学成分和药理活性研究进展 [J]. 中药材 , 2013 , 36 ( 5 ): 843 - 848 .

肖志彬 , 贾韩学 , 刘小雷 . β -谷甾醇药理活性的研究现状 [J]. 世界最新医学信息文摘 , 2015 , 15 ( 8 ): 66 - 68 .

程斌 , 赵春宝 , 张骥 . 槲皮素对高脂血症大鼠的降脂作用 [J]. 中外健康文摘 , 2011 , 8 ( 21 ): 259 - 260 .

翟云鹏 , 汪建云 , 刘耀武 , 等 . 槲皮素对大鼠实验性高血压，高血糖合并高脂血症作用的研究 [J]. 徐州医学院学报 , 2012 , 32 ( 11 ): 719 - 724 .

XIE W , ZHANG Y , WANG N , et al . Novel effects of macrostemonoside A,a compound from Allium macrostemon Bung,on hyperglycemia,hyperlipidemia,and visceral obesity in high-fat diet-fed C57BL/6 mice [J]. Eur J Pharmacol , 2008 , 599 ( 1/3 ): 159 - 165 .

马柳安 , 邱惠 , 玲李荔 , 等 . miRNA通过PPAR和AMPK/SREBPs信号通路调控脂质代谢 [J]. 生命的化学 , 2017 , 37 ( 6 ): 1017 - 1029 .

DAI X , DING M , ZHANG W , et al . Anti-inflammatory effects of different elution fractions of Er-Miao-San on acute inflammation induced by carrageenan in rat paw tissue [J]. Med Sci Monit , 2019 , 25 : 7958 - 7965 .

YANG Q , YU X J , SU Q , et al . Blockade of c-Src within the paraventricular nucleus attenuates inflammatory cytokines and oxidative stress in the mechanism of the TLR4 signal pathway in salt-induced hypertension [J]. Neurosci Bull , 2019 , doi: 10.1007/s12264-019-00435-z http://dx.doi.org/10.1007/s12264-019-00435-z .

MAO D , LI H , ZHANG L , et al . Bilobalide alleviates IL-17-induced inflammatory injury in ATDC5 cells by downregulation of microRNA-125a [J]. J Biochem Mol Toxicol , 2019 , 33 ( 12 ): 1 - 7 .

杨梦思 , 周娜 , 王志钢 , 等 . 转录因子HIF-1 α 及其信号通路在疾病发生中的作用研究进展 [J]. 生物技术通报 , 2016 , 32 ( 8 ): 8 - 13 .

陈艳敏 . 分泌性中耳炎中耳积液中花生四烯酸及其代谢产物和细菌学的研究 [D]. 福州 : 福建医科大学 , 2018 .

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