基于“成分-靶点-通路”网络和分子对接技术的泻火消瘿方治疗格雷夫斯病药效物质基础和作用机制初探

崔国倩; 项艳; 曲晓洋; 相萍萍; 朱粉霞; 谢亚萍

doi:10.14148/j.issn.1672-0482.2021.0275

基于“成分-靶点-通路”网络和分子对接技术的泻火消瘿方治疗格雷夫斯病药效物质基础和作用机制初探

doi: 10.14148/j.issn.1672-0482.2021.0275

南京中医药大学附属中西医结合医院，江苏省中医药研究院国家中医药管理局中药口服释药系统重点实验室，江苏南京 210028

基金项目:

国家自然科学基金 8190414

江苏省中医药研究院院级课题 YNZJ1916

详细信息

作者简介:
崔国倩，女，硕士研究生，E-mail：cuiguoqian0813@163.com

通讯作者:
朱粉霞，女，研究员，主要从事中药药效物质基础研究，E-mail: zfxcjq@126.com

中图分类号: R285.5
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- 被引次数: 0
出版历程
- 收稿日期: 2020-11-02
- 网络出版日期: 2021-12-21
- 刊出日期: 2021-03-10
- 发布日期: 2021-03-15

A Preliminary Study on the Effective Material Basis and Mechanism of Anti-GD of Xiehuo Xiaoying Recipe Based on "Component-Target-Pathway" Network and Molecular Docking Technology

Key Laboratory of Oral Drug Delivery System, State Administration of Traditional Chinese Medicine, Jiangsu Research Institute of Traditional Chinese Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China

摘要

摘要: 目的基于网络药理学和分子对接技术研究泻火消瘿方治疗格雷夫斯病(Graves diseases，GD)的药效物质基础和作用机制。方法通过数据库收集泻火消瘿方中药材的化学成分及作用靶点集，再检索GD相关靶点集。构建泻火消瘿方治疗GD的“药材-成分-靶点”网络及靶点蛋白相互作用(PPI)网络。进行KEGG和GO富集，预测其作用机制，并进行关联性分析。最后将筛选出的活性成分与关键靶点进行分子对接。结果获得泻火消瘿方化合物92个，相应靶点227个。PPI网络筛选出了核心靶点18个。得到KEGG通路192条(P < 0.05)，GO条目2 385个(P < 0.05)，其中BP条目1 988个，CC条目255个，MF条目142个。分子对接结果显示，泻火消瘿方核心成分与潜在关键靶点具有较好的结合活性，与目前可能治疗GD药物的亲和力相近。结论泻火消瘿方相关作用靶点及代谢通路为进一步研究泻火消瘿方治疗GD的药效物质基础及作用机制提供依据。
- 网络药理学 /
- 分子对接 /
- 泻火消瘿方 /
- 格雷夫斯病 /
- 化学成分 /
- 靶点
Abstract: OBJECTIVE Based on network pharmacology and molecular docking technology to study the effective material basis and mechanism of Xiehuo Xiaoying Recipe in the treatment of Graves diseases (GD).METHODS The chemical composition and target set of Chinese medicinal materials of Xiehuo Xiaoying Recipe were collected through the database, and then the target set related to GD was searched. The "medicinal material-chemical composition-target" network and the "target protein-target protein" interaction (PPI) network of Xiehuo Xiaoying Recipe for the treatment of GD were constructed. KEGG and GO enrichment were carried out, to predict its mechanism, and conduct correlation analysis. Finally, the screened active ingredients were molecularly docked with key targets.RESULTS 92 compounds of Xiehuo Xiaoying Recipe and 227 corresponding targets were obtained. PPI network screened out 18 core targets. 192 KEGG pathways were obtained (P < 0.05), and GO function enrichment analysis yielded 2 385 GO entries (P < 0.05), including 1 988 BP entries, 255 CC entries, and 142 MF entries. The Results of molecular docking showed that the core components of Xiehuo Xiaoying Recipe had good binding activities with potential key targets, and their affinity degrees were similar to those of the current drugs that might treat GD.CONCLUSION This study reveals the relevant targets and metabolic pathways of Xiehuo Xiaoying Recipe, and provides a basis for further research on the effective material basis and mechanism of Xiehuo Xiaoying Recipe in the treatment of GD.
- network pharmacology /
- molecular docking /
- Xiehuo Xiaoying Recipe /
- Graves diseases /
- chemical composition /
- target

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图 1 研究思路

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图 2 泻火消瘿方中化学成分的主要结构类型

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图 3 泻火消瘿方反向找靶及治疗GD潜在作用靶点研究

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图 4 泻火消瘿方“药材-成分-靶点”网络图

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图 5 泻火消瘿方干预GD的PPI网络图

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图 6 PPI模块分析

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图 7 PPI网络

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图 8 KEGG富集分析气泡图

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图 9 泻火消瘿方成分-靶点-通路网络图

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图 10 GO分析结果

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图 11 泻火消瘿方与疾病的关联分析

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图 12 泻火消瘿方与细胞、组织的关联分析

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图 13 靶点对接模型

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表 1 靶点信息

靶点	晶体结构	解析度/Å	RMSD/Å	X轴	Y轴	Z轴	口袋大小	结合位点
SRC	2BDF	2.10	0.775 9	-0.774 9	35.143 1	21.325 3	9.000 000	-0.774 9，35.143 1，21.325 3，11.400 0
JUN	2P33	2.10	0.568 4	19.351 1	17.059 2	31.193 0	16.299 999	19.351 1，17.059 2，31.193 0，16.300 0
HSP90AA1	4BQG	1.90	0.562 4	4.308 4	13.652 2	24.145 7	14.700 000	4.308 4，13.652 2，24.145 7，14.700 0
ESR1	5FQR	1.94	0.856 8	16.229 5	26.250 0	65.115 1	15.800 000	16.229 5，26.250 0，65.115 0，15.800 0
HSPA1A	4WV5	2.04	0.776 2	13.455 6	-5.086 0	16.928 9	16.600 000	13.456 6，-5.806 0, 16.928 9, 16.600 0
MAPK14	1OZ1	2.10	0.512 0	20.882 1	23.582 6	22.689 6	11.300 000	20.882 1，23.582 6，22.689 6，11.300 0
PIK3R1	4WAF	2.39	0.641 0	-22.138 2	17.782 7	-42.147 0	37.799 999	-22.138 2，17.782 7，-42.147 0，37.800 0
PARP1	5WRY	2.30	1.210 2	-9.232 4	-9.278 3	12.476 2	22.500 000	-9.232 4，-9.278 3，12.476 2，22.500 0
ESR2	2JJ3	2.28	0.624 4	90.033 4	30.425 1	46.026 3	15.200 000	90.033 4，30.425 1，46.026 3，15.200 0
IGF1R	3NW6	2.20	0.660 4	-13.195 3	-0.588 8	13.437 8	14.600 000	-13.195 3，-0.588 8，13.437 8，1.000 0
PIK3CG	4HVB	2.35	0.524 6	47.223 2	-1.637 7	21.765 2	29.100 000	47.223 2，-1.637 7，21.765 2，29.100 0
TOP2A	5NNE	1.15	0.727 8	49.932 2	12.609 4	15.941 2	11.100 000	49.932 2，12.604 9，15.941 2，11.100 0
F2	3K65	1.85	0.669 1	16.526 2	10.504 1	-26.169 3	11.100 000	16.526 2，10.504 1，-26.169 3，11.100 0
MET	4EEV	1.80	1.070 5	10.207 9	-1.495 2	47.351 7	14.000 000	10.207 9，-1.495 2，47.351 7，14.000 0

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表 2 对接结果

名称	ID	SRC	JUN	HSP90AA1	ESR1	HSPA1A	MAPK14	PIK3R1	PARP1	ESR2	IGF1R	PIK3CG	TOP2A	F2	MET
植物甾醇	E1	-48.343 8	-43.664 0	-101.770 7	-286.003 0	-	-	-85.286 8	-36.289 3	-	-	-40.680 4	-	-	-50.038 4
西托糖苷	D1	-	-	-	-	-	-	-573.425 0	-41.409 8	-	-	-130.756 0	-	-	-
β-谷甾醇	B1	-40.896 8	-23.763 0	-92.737 2	-214.870 0	-	-	-61.613 6	-30.737 8	-	-	-28.913 7	-	-	-44.471 1
豆甾醇葡萄糖苷	F1	-	-67.246 0	-	-	-	-	-214.282 0	-53.857 2	-	-	-	-	-	-
山柰酚	C1	30.697 8	32.781 5	31.885 5	28.987 0	-39.239 5	33.280 3	35.031 6	27.405 8	31.052 7	29.583 2	30.334 3	31.813 0	-69.946 7	33.650 7
齐墩果酸	A1	-110.590 0	-	-	-	-	-	-124.025 0	-	-	-	-51.496 8	-	-	-156.966 0
异荭草素	A2	36.127 9	36.891 7	36.358 1	34.755 2	-43.724 1	35.221 2	37.397 0	31.499 3	35.455 0	34.090 4	33.776 3	34.797 1	-	36.504 5
异牡荆素	LD7	17.846 9	23.381 2	20.149 4	-238.402 0	-	9.197 5	19.829 6	17.665 6	-425.655 0	6.929 9	23.447 0	-	-	23.044 9
熊果酸	XKC16	-105.991 0	-	-	-	-	-	-112.272 0	-	-	-	-49.071 9	-	-	-105.175 0
汉黄芩苷	HQ36	12.504 8	22.111 5	16.598 6	-213.509 0	-	7.292 3	12.484 3	12.117 7	-64.904 9	-20.163 9	19.385 6	-	-	22.603 4
红景天苷	SDH4	17.201 4	18.297 5	16.984 5	14.854 3	-52.447 7	17.658 4	17.181 5	11.513 0	14.553 0	8.913 5	11.835 3	21.608 4	-	16.654 9
Gentirigeoside A	LD12	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Mangiferolic acid	ZM2	-45.185 4	-32.292 0	-129.994 0	-171.121 0	-	-	-82.564 5	-29.799 1	-190.683 0	-	-27.296 2	-	-	-41.908 1
知母皂苷B	ZM15	-	-	-	-	-	-	-	-82.265 2	-	-	-301.189 0	-	-	-
薯蓣皂苷	CSL3	-	-	-	-	-	-	-	-80.159 9	-	-	-	-	-	-
当药苦苷	LD10	-11.129 3	-12.720 0	-13.955 7	-11.554 6	-234.950 0	-14.914 8	-10.045 3	-14.744 8	-28.467 3	-31.201 8	-5.388 9	-	-	-14.256 4
Gentisein	LD16	31.147 0	26.711 7	27.237 4	32.068 1	-17.256 6	28.122 1	24.654 9	23.428 6	32.822 5	30.042 6	24.671 8	30.232 2	-94.370 8	28.525 4
迷迭香酸	XKC15	45.955 2	50.065 2	50.740 5	46109 0	3.536 3	50.256 1	43.563 8	41.679 5	43.943 0	41.884 3	49.809 7	31.035 3	-	50.473 6
日当药黄素	LD3	19.843 0	26.570 3	18.850 5	-230.013 0	-	-	23.391 8	17.876 8	-	0.229 3	19.874 8	-	-	23.849 8
表小檗碱	HQ29	-	-	-	-	-	-	-	-	-	-	-	-	-	-
豨莶苷	BH7	-	-76.902 0	-	-	-	-	-	-59.458 9	-	-	-69.755 0	-	-	-
Gentirigenic acid	LD2	-	-	-	-	-	-	-305.722 0	-	-	-	-57.984 4	-	-	-175.569 0
龙胆苦苷	LD11	-16.080 5	-5.570 3	-19.011 3	-24.511 6	-147.124 0	-16.792 4	-16.732 8	-21.297 3	-21.061 8	-27.305 9	-17.546 9	-321.938 0	-	-16.9158 6
当药宁	LD14	29.424 2	28.056 3	29.1126 4	33.232 6	-37.190 5	29.217 5	22.693 9	26.937 9	34.872 4	28.326 9	25.263 9	28.052 0	-266.929 0	30.839 7
α-菠菜甾醇	XKC5	-55.010 4	-42.509 0	-205.220 0	-199.604 0	-	-	-71.792 2	-41.943 3	-283.189 0	-205.271 0	-35.029 1	-	-	-54.022 0
Stigmast-7-entol	XKC11	16.533 5	-39.402 0	-159.965 0	-180.631 0	-	-	-38.108 8	-38.352 1	-	-197.057 0	-30.470 2	-	-254.492 0	-47.605 8
黄芩新素	HQ13	16.533 5	16.903 8	20.344 2	-7.992 5	-120.109 0	-120.109 0	27.774 4	12.195 3	4.073 4	3.892 9	20.107 3	-	-	18.054 3
异海松酸	BH1	-31.667 6	-21.546 0	-27.422 0	-41.838 4	-466.387 0	-466.387 0	-19.897 9	-24.212 6	-42.018 4	-86.181 3	-26.912 1	-	-	-29.974 3
红花素	HQ7	35.639 0	34.549 9	37.892 7	38.326 0	-23.810 5	-23.810 5	41.546 1	29.040 4	42.951 0	31.730 1	32.688 2	34.567 0	-152.678 0	39.945 5
甲亢平	Y1	2.809 9	2.428 4	3.600 4	4.257 8	-8.554 8	-8.554 8	-2.777 7	-0.109 9	5.173 2	3.547 5	1.633 6	6.007 1	-11.885 5	3.079 8
丙硫氧嘧啶	Y2	18.158 8	17.712 5	18.151 6	17.517 6	3.338 1	3.338 1	13.504 3	10.578 3	15.628 0	17.043 1	18.645 3	20.882 4	16.945 1	17.003 1
甲巯咪唑	Y3	-4.320 8	-4.686 1	-4.910 3	-2.619 2	-5.288 9	-5.288 9	-4.9534	-7.567 8	-3.681 3	-4.237 1	-7.554 6	-1.715 2	0.138 7	-4.436 3
成功比例		0.724 138	0.724 140	0.655 172	0.655 172	0.379 310	0.379 3	0.827 586	0.827 586	0.517 241	0.551 724	0.862 069	0.275 862	0.172 414	0.758 621
大于Y1的个数		11	11	11	7	1	10	12	11	7	9	11	7	0	11
大于Y2的个数		7	10	9	6	1	7	10	11	6	6	10	7	0	10
大于Y3的个数		11	11	11	7	1	10	11	11	8	10	12	7	0	11
大于Y1/%		0.379 310	0.379 310	0.379 310	0.241 379	0.034 481	0.344 828	0.413 793	0.379 310	0.241 379	0.310 345	0.379 310	0.2471 379	0.000 000	0.379 310
大于Y2/%		0.241 379	0.344 828	0.310 345	0.206 897	0.034 481	0.241 379	0.344 828	0.379 310	0.206 897	0.206 897	0.344 828	0.2471 379	0.000 000	0.344 828
大于Y2/%		0.379 310	0.379 310	0.379 310	0.241 379	0.034 481	0.344 828	0.379 310	0.379 310	0.275 862	0.344 282	0.413 793	0.2471 379	0.000 000	0.379 310
原配体		15.524 1	31.773 1	19.827 0	49.536 1	10.521 2	1.378 4	2.738 190	-2.013 430	28.278 4	-31.680 1	4.484 9	11.259 7	21.437 8	-22.202 5
优于原配体		0.476 190	0.190 480	0.421 053	0	0	0.769 231	0.333 333	0.458 333	0.400 000	0.812 5	0.440 000	0.875 000	0.000 000	0.590 909

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