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Purpose <p>Hydrocephalus, a debilitating neurological condition characterized by the accumulation of cerebrospinal fluid (CSF) in the brain’s ventricles, causes neuroinflammation, oxidative stress, and cognitive impairments. Despite advancements in surgical interventions, the lack of effective pharmacological therapies requires the exploration of alternative therapeutic approaches. The present study investigated the potential therapeutic effects of diosmin, a bioflavonoid glycoside, on hydrocephalus via network pharmacology, molecular docking and dynamic simulations. Diosmin was chosen because of emerging evidence of neuroprotective potential and its well established vascular- protective and anti-inflammatory properties.</p> Methods <p>A computational framework integrating target identification and molecular interaction analysis was used. Between diosmin and hydrocephalus common protein targets were screened, ranked, and evaluated for pathway involvement. Molecular docking was performed to predict diosmin–protein interactions, and the highest-affinity complex was further analyzed using a 100 nanoseconds (ns) molecular dynamics simulation.</p> Results <p>Thirty-four common proteins were identified, with EGFR, TNF, TP53, PTGS2 GSK3B and MMP9 highlighted as key regulators of neuroinflammatory and ECM-related pathways. The KEGG pathway enrichment analysis highlighted significant pathways, such as the PI3-Akt signaling pathway and proteoglycans in cancer, which corelates with hydrocephalus pathophysiology. Diosmin exhibited strong predicted binding affinity towards these targets. The diosmin–GSK3B, –PTGS2, –MMP9 complexes showed notable stability in molecular dynamics simulations, with consistent RMSD, stable radius of gyration, and sustained hydrogen bonding throughout the trajectory.</p> Conclusion <p>With the computational insights, this study demonstrates that diosmin may have a multitarget therapeutic potential in hydrocephalus by modulating neuroinflammation and ECM remodeling. These findings provide a foundation for further preclinical validation and drug development efforts.</p> Graphical Abstract <p></p>

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Diosmin as a Multitarget Therapeutic for Hydrocephalus: Insights from Network Pharmacology, Docking, and MD Simulation

  • 期刊论文

  • 发表日期：

    2026年5月20日

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  • Davood Ahmad Sheergojree,
  • Ajay Singh Kushwah,
  • Atul Kabra,
  • Hassan A. Madkhali,
  • Mohd Nazam Ansari,
  • Yassine Riadi

摘要

Purpose

Hydrocephalus, a debilitating neurological condition characterized by the accumulation of cerebrospinal fluid (CSF) in the brain’s ventricles, causes neuroinflammation, oxidative stress, and cognitive impairments. Despite advancements in surgical interventions, the lack of effective pharmacological therapies requires the exploration of alternative therapeutic approaches. The present study investigated the potential therapeutic effects of diosmin, a bioflavonoid glycoside, on hydrocephalus via network pharmacology, molecular docking and dynamic simulations. Diosmin was chosen because of emerging evidence of neuroprotective potential and its well established vascular- protective and anti-inflammatory properties.

Methods

A computational framework integrating target identification and molecular interaction analysis was used. Between diosmin and hydrocephalus common protein targets were screened, ranked, and evaluated for pathway involvement. Molecular docking was performed to predict diosmin–protein interactions, and the highest-affinity complex was further analyzed using a 100 nanoseconds (ns) molecular dynamics simulation.

Results

Thirty-four common proteins were identified, with EGFR, TNF, TP53, PTGS2 GSK3B and MMP9 highlighted as key regulators of neuroinflammatory and ECM-related pathways. The KEGG pathway enrichment analysis highlighted significant pathways, such as the PI3-Akt signaling pathway and proteoglycans in cancer, which corelates with hydrocephalus pathophysiology. Diosmin exhibited strong predicted binding affinity towards these targets. The diosmin–GSK3B, –PTGS2, –MMP9 complexes showed notable stability in molecular dynamics simulations, with consistent RMSD, stable radius of gyration, and sustained hydrogen bonding throughout the trajectory.

Conclusion

With the computational insights, this study demonstrates that diosmin may have a multitarget therapeutic potential in hydrocephalus by modulating neuroinflammation and ECM remodeling. These findings provide a foundation for further preclinical validation and drug development efforts.

Graphical Abstract