Exploring the mechanism and function of Xiasangju in the treatment of xerophthalmia based on network pharmacology and experimental validation

LI Jinliang; HU Shuangfei; MENG Fenzhao; LI Peibo; WU Hao; PENG Wei; SU Weiwei; WANG Yonggang; SUN Weiguang

doi:10.13471/j.cnki.acta.snus.2023E038

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Exploring the mechanism and function of Xiasangju in the treatment of xerophthalmia based on network pharmacology and experimental validation

Research articles | 更新时间：2024-01-25

- Exploring the mechanism and function of Xiasangju in the treatment of xerophthalmia based on network pharmacology and experimental validation
- Acta Scientiarum Naturalium Universitatis Sunyatseni Vol. 63, Issue 1, Pages: 56-65(2024)
- 作者机构：
  
  1.中山大学生命科学学院 / 广东省中药上市后质量与药效再评价工程技术研究中心 / 广东省热带亚热带植物资源重点实验室，广东广州 510275
  2.广州白云山星群（药业）股份有限公司，广东广州 510288
- 作者简介：
- 基金信息：
- DOI：10.13471/j.cnki.acta.snus.2023E038
  CLC： R285.5
- Published：25 January 2024，
  
  Published Online：23 October 2023，
  
  Received：11 July 2023，
  
  Accepted：07 August 2023
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李进良,胡双飞,蒙奋兆等.夏桑菊防治干眼症的网络药理学机制及实验验证[J].中山大学学报(自然科学版)(中英文),2024,63(01):56-65.

LI Jinliang,HU Shuangfei,MENG Fenzhao,et al.Exploring the mechanism and function of Xiasangju in the treatment of xerophthalmia based on network pharmacology and experimental validation[J].Acta Scientiarum Naturalium Universitatis Sunyatseni,2024,63(01):56-65.
李进良,胡双飞,蒙奋兆等.夏桑菊防治干眼症的网络药理学机制及实验验证[J].中山大学学报(自然科学版)(中英文),2024,63(01):56-65. DOI： 10.13471/j.cnki.acta.snus.2023E038.

LI Jinliang,HU Shuangfei,MENG Fenzhao,et al.Exploring the mechanism and function of Xiasangju in the treatment of xerophthalmia based on network pharmacology and experimental validation[J].Acta Scientiarum Naturalium Universitatis Sunyatseni,2024,63(01):56-65. DOI： 10.13471/j.cnki.acta.snus.2023E038.

摘要

采用网络药理学、分子对接及细胞实验探究了夏桑菊防治干眼症的作用机制。通过超快速高效液相色谱串联三重四极杆飞行时间质谱（UFLC-Triple-TOF-MS/MS）分析夏桑菊的化学成分，借助网络药理学相关数据库与分析平台预测夏桑菊有效成分靶点及检索疾病相关靶点，并利用cytoscape软件及STRING平台构建网络。采用DAVID数据库进行GO和KEGG通路富集分析，将关键靶点前4位与其对应活性成分进行分子对接。体外构建干眼症高渗模型验证核心靶点。共鉴定出61种化学成分，筛选得到24种有效成分可能与干眼症相关的315个潜在的靶点蛋白具有相互作用；筛选出夏桑菊作用的关键活性成分迷迭香酸、蒙花苷及绿原酸等和关键靶点为

TNF-α、Caspase1、IL-6

以及

IL-1β

；富集结果表明，夏桑菊治疗干眼症靶点主要集中在AGE-RAGE、TNF等多个信号通路。3种有效成分在细胞实验中不仅显著抑制人角膜上皮细胞活性降低，提升高渗下细胞的移行能力，而且有效抑制高渗诱导下人角膜上皮细胞中

Caspase1、IL-1β

基因的表达及 TNF-α 蛋白分泌水平。结果表明夏桑菊中的迷迭香酸、蒙花苷及绿原酸3种主要的活性成分，发挥了高渗诱导下对人角膜上皮细胞保护及修复作用，降低了细胞TNF-α蛋白水平

及Caspase1

、

IL-1β

mRNA的相对表达。

Abstract

The study was to explore the mechanism of action of Xiasangju in the treatment of xerophthalmia by using network pharmacology， molecular docking method and cell experiments. The chemical components of Xiasangju were analyzed by ultra-fast high performance liquid chromatography tandem triple quadrupole time-of-flight mass spectrometry （UFLC-Triple-TOF-MS/MS）. Targets of active components were predicted and disease related targets were retrieved with the help of network pharmacologic database and analysis platform. The network was built using cytoscape software and STRING platform. GO and KEGG pathway enrichment analysis was performed using the DAVID database， and the top 4 key targets were matched with their corresponding active component molecules. A hypertonic model of dry eye was constructed in vitro to verify the core target. A total of 61 chemical components were identified， and 24 effective components potentially related to xerophthalmia were selected for further screening. These 24 components were found to interact with 315 potential target proteins. Among them， the key active components of Xiasangju were identified as rosmarinic acid， linarin and chlorogenic acid， which targeted

TNF-α

，

Caspase1

，

IL-6

， and

IL-1β

. Enrichment analysis revealed that the therapeutic targets of Xiasangju for xerophthalmia were concentrated in multiple biological processes， including the AGE-RAGE signaling pathway， TNF signaling pathway， and others. In cell experiments， these three active components not only significantly inhibited cell viability reduction but also enhanced the migration ability of high osmolarity-induced corneal epithelial cells. They effectively suppressed the expression of

Caspase1

and

IL-1β

genes， as well as the secretion level of TNF-α protein in high osmolarity-induced human corneal epithelial cells. The main active components， rosmarinic acid， linarin and chlorogenic acid， in Xiasangju exerted protective and reparative effects on human corneal epithelial cells under high osmolarity conditions. They reduced the protein level of TNF-α and the relative expression of

Caspase1

and

IL-1β

mRNA.

关键词

夏桑菊干眼症网络药理学分子对接实验验证

Keywords

Xiasangjuxerophthalmianetwork pharmacologymolecular dockingexperimental validation

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Related Institution

Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-marketed TCM， Guangdong Key Laboratory of Plant Resources， School of Life Sciences， Sun Yat-sen University

School of Life Sciences,Sun Yat-sen University

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College of Pharmacy,Jinan University

Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-marketed TCM / Guangdong Key Laboratory of Plant Resources / School of Life Sciences， Sun Yat-sen University

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