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1.南京中医药大学 医学院·整合医学学院,南京 210023
2.河南中医药大学 第一附属医院,郑州 450000
林子璇,硕士,医师,从事中药药理学研究,E-mail:3356376831@qq.com
赵玉男,教授,从事中药药理学研究,E-mail:zhaoyunan-js@163.com
修回日期:2020-03-12,
网络出版日期:2020-05-27,
纸质出版日期:2020-08-05
移动端阅览
林子璇,刘飞祥,赵玉男等.人参“补气”和三七“补血”抗疲劳的共同作用机制和效用比较[J].中国实验方剂学杂志,2020,26(15):81-89.
LIN Zi-xuan,LIU Fei-xiang,ZHAO Yu-nan,et al.Anti-fatigue Analysis of Common Mechanisms of Interaction of Ginseng Radix et Rhizoma "Tonifying Qi" and Notoginseng Radix et Rhizoma "Enriching Blood"[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(15):81-89.
林子璇,刘飞祥,赵玉男等.人参“补气”和三七“补血”抗疲劳的共同作用机制和效用比较[J].中国实验方剂学杂志,2020,26(15):81-89. DOI: 10.13422/j.cnki.syfjx.20201540.
LIN Zi-xuan,LIU Fei-xiang,ZHAO Yu-nan,et al.Anti-fatigue Analysis of Common Mechanisms of Interaction of Ginseng Radix et Rhizoma "Tonifying Qi" and Notoginseng Radix et Rhizoma "Enriching Blood"[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(15):81-89. DOI: 10.13422/j.cnki.syfjx.20201540.
目的
2
基于网络药理学技术,分析人参“补气”和三七“补血”抗疲劳的共同活性成分、潜在靶基因和通路,并分别选取人参总皂苷和三七总皂苷两种化合物成分,对筛选出的关键靶基因进行体外实验验证。
方法
2
通过中药系统药理学数据库及分析平台(TCMSP),筛选人参和三七的主要有效活性成分和相关作用靶标;依靠GeneCards综合数据库和人类孟德尔遗传综合数据库(OMIM),建立疲劳基因的数据集;通过R软件获取药物和疾病的交集基因;采用Cytoscape软件建立有效活性成分-药物靶标-疲劳靶基因之间的调控网络;通过STRING 11.0软件构建交集基因的PPI网络,采用CytoHubba软件和马修斯相关系数(MCC)算法筛选核心基因。基于网络分析结果,将24只SPF级ICR雄性小鼠随机分为空白组,人参总皂苷组(0.08 g·kg
-1
)和三七总皂苷组(0.08 g·kg
-1
),并给予相应药物治疗3周,实时荧光定量PCR(Real-time PCR)检测肌肉组织中核心基因mRNA表达。
结果
2
从TCMSP共筛选出20个有效活性成分,181个药物靶标,经R软件与GeneCards和OMIM综合数据库比对,共获取33个疾病与药物的交集基因;MCC算法共筛选出芳基烃受体(AHR),雄激素受体(AR),谷胱甘肽S-转移酶P1(GSTP1),半胱氨酸蛋白酶-3(Caspase-3),细胞色素P450酶3A4(CYP3A4),细胞间黏附分子1(ICAM1)和核转录因子-
κ
B抑制剂
α
(NFKBIA)等10个核心基因。人参总皂苷和三七总皂苷对GSTP1和ICAM1基因无明显影响,但能明显抑制AHR,CYP3A4,Caspase-3,NFKBIA和AR的表达(
P
<
0.05,
P
<
0.01),且人参总皂苷和三七总皂苷组之间的抗疲劳效用没有明显差异。
结论
2
通过网络分析和实验验证,揭示了人参和三七抗疲劳的共同作用机制,可能与对AHR,CYP3A4和Caspase-3等相关基因的调节有关,且二者抗疲劳的效用没有显著差异。
Objective
2
To analyze the common active ingredients, potential target genes and pathways of Ginseng Radix et Rhizoma "Tonifying Qi" and Notoginseng Radix et Rhizoma "Enriching blood" in alleviating fatigue based on the network pharmacology technology. And the compound ingredients of total Ginsenoside Ginseng Root and Notoginseng total Saponins were selected to verify the core target genes
in vitro
.
Method
2
The main active ingredients and related targets of Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma were screened by traditional Chinese medicine systems pharmacology (TCMSP). The data of fatigue genes were established by GeneCards comprehensive database and Human Mendelian Genetic Integrated Database(OMIM). Depending, The data sets of fatigue-related genes are established based on the data bank of GeneCards and OMIM. The intersecting genes of drugs and disease were obtained by R software. Cytoscape software was used to establish the regulatory network among the active ingredients, drug targets and fatigue-related genes. PPI network of intersecting genes was constructed by STRING 11.0 software, and the core genes were screened by CytoHubba software and Matthews correlation coefficient (MCC) algorithm. Based on the results of network analysis, 24 male SPF ACR mice were randomly divided into control group, total Ginsenoside Ginseng Root group (0.08 g·kg
-1
) and Notoginseng total Saponins group (0.08 g·kg
-1
). The corresponding drugs were given for 3 weeks. The expressions of core genes in muscle tissue were detected by real-time fluorescence quantitative PCR.
Result
2
The 20 active components and 181 drug targets were screened from TCMSP. 33 intersecting genes of diseases and drugs were obtained when compared with GeneCards and OMIM comprehensive database using R software. 10 core genes including aryl hydrocarbon receptor (AHR), androgen receptor (AR), glutathione S-transferase P1 (GSTP1), cysteine proteinase-3(Caspase-3), cytochrome p450 enzyme 3A4 (CYP3A4), intercellular adhesion molecule 1 (ICAM1) and nuclear factor kappa B inhibitor alpha (NFKBIA) were screened out by the algorithm of MCC. Total Ginsenoside Ginseng Root and Notoginseng total Saponins had no significant effect on GSTP1 and ICAM1 genes, but they could significantly inhibit the expressions of AHR, CYP3A4, Caspase-3, NFKBIA and AR (
P
<
0.05,
P
<
0.01), and there were no significant difference in anti-fatigue effect between total Ginsenoside Ginseng Root and Notoginseng total Saponins groups.
Conclusion
2
The mechanism of anti-fatigue of Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma may be related to the regulation of AHR, CYP3A4 and Caspase-3 genes, and there is no significant difference in their anti-fatigue effects, through the analysis of network and experimental verification.
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