Z-Ligustilide ameliorates retinitis pigmentosa <italic style="font-style: italic">via</italic> inhibiting PI3K/AKT-inflammation axis: Validation based on network pharmacology and molecular docking

XIAO Weizuo; GE Lingling; A Luodan; DENG Jiaxing; HUO Shujia; XU Haiwei

doi:10.16016/j.2097-0927.202507084

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Z-Ligustilide ameliorates retinitis pigmentosa via inhibiting PI3K/AKT-inflammation axis: Validation based on network pharmacology and molecular docking

Pharmacy | 更新时间：2025-12-25

- Z-Ligustilide ameliorates retinitis pigmentosa via inhibiting PI3K/AKT-inflammation axis: Validation based on network pharmacology and molecular docking
- Journal of Army Medical University Vol. 47, Issue 20, Pages: 2569-2580(2025)
- 作者机构：
  
  1.陆军军医大学（第三军医大学）第一附属医院眼科，重庆
  2.南部战区总医院眼科，广东广州
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation of China(31930068;82271104)
- DOI：10.16016/j.2097-0927.202507084
  CLC： R285.5;R319;R774.13
- Received：25 July 2025，
  
  Revised：2025-09-28，
  
  Accepted：29 September 2025，
  
  Published：30 October 2025
- 稿件说明：
移动端阅览
肖维作，葛玲玲，阿洛丹，等.Z-藁本内酯通过抑制PI3K/AKT信号通路延缓视网膜色素变性：基于网络药理学与分子对接验证［J］.陆军军医大学学报，2025，47（20）：2569-2580.DOI：10.16016/j.2097-0927.202507084.

XIAO W Z，GE L L，A L D，et al.Z-Ligustilide ameliorates retinitis pigmentosa via inhibiting PI3K/AKT-inflammation axis： Validation based on network pharmacology and molecular docking［J］.J Army Med Univ，2025，47（20）：2569-2580.DOI：10.16016/j.2097-0927.202507084.
肖维作，葛玲玲，阿洛丹，等.Z-藁本内酯通过抑制PI3K/AKT信号通路延缓视网膜色素变性：基于网络药理学与分子对接验证［J］.陆军军医大学学报，2025，47（20）：2569-2580.DOI：10.16016/j.2097-0927.202507084. DOI：

XIAO W Z，GE L L，A L D，et al.Z-Ligustilide ameliorates retinitis pigmentosa via inhibiting PI3K/AKT-inflammation axis： Validation based on network pharmacology and molecular docking［J］.J Army Med Univ，2025，47（20）：2569-2580.DOI：10.16016/j.2097-0927.202507084. DOI：

摘要

目的

研究Z-藁本内酯（Z-ligustilide， Z-LIG）治疗视网膜色素变性（retinitis pigmentosa， RP）的作用靶点和分子机制。

方法

通过整合GeneCards、TargetNet等多数据库，筛选出RP与Z-LIG的共同靶点。利用STRING数据库构建蛋白质-蛋白质相互作用（protein-protein interaction， PPI）网络，并通过Cytoscape进行拓扑分析以识别核心靶点。利用DAVID数据库对核心靶点进行基因本体（GO）功能富集和京都基因与基因组百科全书（KEGG）路径富集分析；访问PubChem数据库进行分子对接验证Z-LIG与核心靶点的结合能力。将雄性rd10小鼠按照随机数字表法分为2组：对照组（Con组，

=5）和Z-LIG治疗组（Z-LIG组，

=5），通过视觉电生理和行为学检测验证Z-LIG对rd10小鼠视力的保护作用，并通过Western blot和RT-qPCR检测探究药物作用的分子机制。

结果

筛选得到RP和Z-LIG交叉靶点共66个，PPI网络数据分析筛选得到核心靶点55个，GO富集分析涵盖3个维度细胞组分（cellular component， CC）、分子功能（molecular function， MF）和包含炎症反应的生物过程（biological process， BP）共623个条目；包含PI3K-AKT信号通路的KEGG通路富集至124个条目。分子对接提示Z-LIG可通过氢键与RP相关核心靶点（EGFR、STAT3等）高亲和力特异性结合。动物实验表明，与对照组相比，Z-LIG组rd10小鼠在黑白箱实验中更倾向于黑暗环境（

0.05）；视网膜电图（electroretinogram， ERG）的A、B波幅值显著升高（

0.05）；外核层层数更多，凋亡数目更少，小胶质细胞活化更少（

0.05）；且视网膜中p-PI3K/PI3K和p-AKT/AKT均显著下降（

0.05）；同时促炎因子IL-1β和IL-6的mRNA表达水平显著下调（

0.05）。

结论

Z-LIG可能通过抑制PI3K/AKT-炎症轴发挥对rd10小鼠视网膜的保护作用从而延缓视网膜变性。

Abstract

Objective

To investigate the potential therapeutic targets and underlying molecular mechanisms of Z-ligustilide (Z-LIG) in treating retinitis pigmentosa (RP).

Methods

By integrating multiple databases

such as GeneCards and TargetNet

common targets for RP and Z-LIG were identified. Protein-protein interaction (PPI) network analysis of the targets was conducted using the STRING database and analyzed in Cytoscape to identify core targets. The DAVID database was employed for the functional enrichment analysis of Gene Ontology (GO) and the pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) for the core targets. The PubChem database was accessed for molecular docking verification to validate the binding affinity between Z-LIG and the core targets. Finally

male rd10 mice were randomly divided into a control group (

=5) and a Z-LIG treatment group (

=5). The protective effect of Z-LIG on the visual function in rd10 mice was verified through visual electrophysiology and behavioral tests. Western blotting and RT-qPCR were utilized to investigate the molecular mechanism of action.

Results

A total of 66 shared targets between RP and Z-LIG were identified through

the screening process. PPI network analysis identified 55 key targets. GO enrichment analysis yielded 623 terms

which covering 3 dimensions

including cellular component (CC)

molecular function (MF)

and biological process (BP)

such as inflammatory response. KEGG pathway enrichment analysis further concentrated 124 terms

which were enriched in the PI3K-Akt signaling pathway. Molecular docking suggested that Z-LIG could specifically bind with high affinity to RP-related core targets (such as EGFR and STAT3)

via

hydrogen bonds. In animal experiments

compared to the control group

the rd10 mice from the Z-LIG group showed a greater preference for the dark environment in the light/dark transition test (

0.05)

exhibited significantly higher amplitudes of A-wave and B-wave in electroretinogram (ERG) (

0.05)

greater number of outer nuclear layers

with fewer apoptotic cells and less microglial activation (

0.05)

demonstrated obviously reduced protein levels of p-PI3K/PI3K and p-AKT/AKT in the retina (

0.05)

and had notably down-regulated mRNA levels of pro-inflammatory cytokines IL-1β and IL-6 (

0.05).

Conclusion

Z-LIG may exert a protective effect on the retina of rd10 mice by inhibiting the activation of the PI3K/AKT-inflammatory axis

thereby delaying retinal degeneration.

关键词

Keywords

references

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Z-Ligustilide ameliorates retinitis pigmentosa via inhibiting PI3K/AKT-inflammation axis: Validation based on network pharmacology and molecular docking

DOI：10.16016/j.2097-0927.202507084

摘要

Abstract

关键词

Keywords

references