羟基红花黄色素A对帕金森细胞模型的保护作用及其网络药理学分析

doi:10.5246/jcps.2020.12.078

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (12): 880-895.DOI: 10.5246/jcps.2020.12.078

羟基红花黄色素A对帕金森细胞模型的保护作用及其网络药理学分析

李双¹^,³, 郭春燕¹^,²^,^*(), 李双双¹, 尤斯涵¹, 余秀娟¹

1. 河北北方学院药学系, 河北张家口 075000
2. 河北省神经药理学重点实验室, 河北张家口 075000
3. 河北师范大学生命科学学院, 河北石家庄 050024

收稿日期:2020-09-15 修回日期:2020-10-20 接受日期:2020-11-01 出版日期:2020-12-30 发布日期:2020-12-30
通讯作者: 郭春燕
作者简介:
+ Tel.: +86-18931316689, E-mail: 18931316689@163.com
基金资助:
Education Department of Hebei Province (Grant No. ZD2019107).

Protective effect of hydroxysafflor yellow A on Parkinson cell model and its network pharmacology analysis

Shuang Li¹^,³, Chunyan Guo¹^,²^,^*(), Shuangshuang Li¹, Sihan You¹, Xiujuan Yu¹

1 Department of Pharmacy, HeBei North University, Zhangjiakou 075000, China
2 Hebei Key Laboratory of Neuropharmacology, Zhangjiakou 075000, China
3 College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, China

Received:2020-09-15 Revised:2020-10-20 Accepted:2020-11-01 Online:2020-12-30 Published:2020-12-30
Contact: Chunyan Guo

About author:

Chunyan Guo, Ph.D., Professor of Chemistry of Hebei North University, Supervisor of Master Students, is currently the member of Science and Technology Branch of Academic Committee. Dr. Guo is also the Executive Director of Hebei Pharmacology Society. In 2012, Dr. Guo went to University of Manitoba as a visiting scholar. Dr. Guo's main research direction includes analysis of active components and its derived metabolites of medicinal natural products in vivo. She held Science and Technology Support Plan Projects of Hebei Province, and has won the third prize of Science and Technology Progress of Hebei Province. At present, she mainly undertakes the teaching works of Analytical Chemistry, Pharmaceutical Analysis, Biopharmaceutical Analysis and Drug Quality Testing Technology.

摘要/Abstract

摘要：

羟基红花黄色素A是中药红花的主要活性成分, 具有活血通经、散瘀止痛的功效, 同时对血瘀风动帕金森病也有着确切的治疗效果, 但当前研究多集中于单一的信号通路, 不利于药物的临床转化和推广。本研究采用鱼藤酮构建PD细胞模型, 通过细胞活力和线粒体膜电位评价HSYA对PD细胞模型的保护作用。利用TTD数据库查询PD相关治疗靶点, Swiss Target Prediction数据库查询HSYA相关靶点, STRING数据库查询共同靶点的基因相互作用关系, ClueGO对共同靶点及其相互作用靶点进行通路富集分析, 探索综合干预机制。结果表明, 鱼藤酮能成功构建PD细胞模型, HSYA对PD细胞模型有明显的保护作用。通过网络药理学分析, 查询到PD相关治疗靶点36个, HYSA相关靶点88个。PD和HSYA的共同靶标为FKBP1A、HTR1A、SLC6A4和SLC6A3, 通过REACTOME对4个共同靶标及其相互作用靶标进行富集分析, 得到8个细胞信号通路, 通过生物过程途径富集分析得到6个细胞生物过程。

关键词: 羟基红花黄色素A, 帕金森, 网络药理学

Abstract:

As an effective component of safflower, hydroxysafflor yellow A (HSYA) has the effect of promoting blood circulation, removing blood stasis, and relieving pain, and it has a certain effect on blood stasis and wind-induced Parkinson’s disease (PD). However, the current research mostly involves a single intervention mechanism, which is not conducive to the clinical transformation of this type of drugs. In the present study, rotenone was used to construct a PD cell model, and the protective effect of HSYA on the PD cell model was evaluated by cell viability and mitochondrial membrane potential. TTD database was used to query PD-related therapeutic targets, Swiss Target Prediction database to query HSYA-related targets, STRING database was used to search the gene interaction relationship of common targets, and ClueGO pathway was adopted to enrich and analyze common targets and their interaction targets, as well as to explore the comprehensive intervention mechanism. The results showed that rotenone could successfully establish the PD cell model, and HSYA had significant protective effect on PD cell model. Through the network pharmacological analysis, 36 PD-related therapeutic targets and 88 HSYA-related targets were queried. The common targets of PD and HSYA were FKBP1A, HTR1A, SLC6A4 and SLC6A3. To enrich four common targets and their interaction targets through REACTOME pathway, eight cell signal pathways were obtained, and six cell biological processes were obtained through biological process pathway enrichment.

Key words: Hydroxysafflor yellow A, Parkinson's disease, Network pharmacology

Supporting:

李双, 郭春燕, 李双双, 尤斯涵, 余秀娟. 羟基红花黄色素A对帕金森细胞模型的保护作用及其网络药理学分析[J]. 中国药学(英文版), 2020, 29(12): 880-895.

Shuang Li, Chunyan Guo, Shuangshuang Li, Sihan You, Xiujuan Yu. Protective effect of hydroxysafflor yellow A on Parkinson cell model and its network pharmacology analysis[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(12): 880-895.

图/表 11

Figure 1. MTT analysis of cell viability in SH-SY5Y cells treated with different concentrations (A) of rotenone at different time points (B). #P < 0.05, ##P < 0.01, ###P < 0.001, compared with control.

Figure 2. Determination of α-synuclein by ELISA. SH-SY5Y cells were treated with 250 nM rotenone for 24 h as a model group. #P < 0.05, ##P < 0.01, ###P < 0.001, compared with control.

Figure 3. Δψ assessed by fluorescence microscopy (× 400). SH-SY5Y cells were treated with 250 nM rotenone for 24 h as a model group.

Figure 4. MTT analysis of cell viability in SH-SY5Y cells treated with drugs for 24 h. SH-SY5Y cells were treated with 250 nM rotenone for 24 h as a model group. #P < 0.05, ##P < 0.01, ###P < 0.001, compared with control; *P < 0.05, **P < 0.01, ***P < 0.001, compared with model.

Figure 5. Δψ assessed by fluorescence microscopy (× 400). SH-SY5Y cells were treated with 250 nM rotenone for 24 h as a model group.

Table 1. PD-related therapeutic targets.

Table 2. HSYA-related therapeutic targets.

Table 3. Possible targets of HSYA intervention in PD.

Figure 6. Correlation targets network at the common target of PD and SHYA. Correlation targets network of FKBP1A (A). Correlation targets network of HTR1A (B). Correlation targets network of SLC6A4 (C). Correlation targets network of SLC6A3 (D). Correlation targets network of all related genes (E).

Figure 7. ClueGO analysis of all related target genes. REACTOME pathways of categories were generated for all related targets. GO terms are represented as nodes, and the node size represents the term enrichment significance (A). The node pie charts represent the molecular function and reactome analysis of these targets (B).

Figure 8. ClueGO analysis of all related target genes. Biological process of categories was generated for all related targets. GO terms are represented as nodes, and the node size represents the term enrichment significance (A). The node pie charts represent the molecular function and reactome analysis of these targets (B).

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羟基红花黄色素A对帕金森细胞模型的保护作用及其网络药理学分析

Protective effect of hydroxysafflor yellow A on Parkinson cell model and its network pharmacology analysis

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