The Small Molecule Compound Eupalinolide B Ameliorates Depressive Behaviors and Neuropathic Pain in Mice With Spared Nerve Injury: Integrating Network Pharmacology, Molecular Docking, Bioinformatics, Molecular Dynamics Simulation and Experimental Verification.

Overview

1. Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2. Institute of Anesthesiology & Pain (IAP), Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, China
3. Department of Anesthesiology, Wenchang People's Hospital, Wenchang, China

Abstract

Background: Neuropathic pain (NP) frequently co‐occurs with depression (DP), exhibiting complex pathogenesis and limited clinical treatment options. This study aims to investigate the efficacy of Eupalinolide B (EB) in alleviating NP co‐occurring with DP and its potential molecular mechanisms.

Methods: Combining network pharmacology, molecular docking, and molecular dynamics simulations to screen potential targets for EB, validated through transcriptomic data. Using a sciatic nerve branch‐preserving injury (SNI) mouse model, we assessed pain and depression‐like behaviors through von Frey testing, hot plate testing, tail suspension testing, forced swimming testing, and open field testing. Concurrently, Western blotting, immunofluorescence, and Nissl staining were employed to analyze relevant molecules and neuropathological alterations.

Results: Network pharmacology and bioinformatics analysis identified EGFR, PTGS2, and JUN as the key targets for EB in treating NP combined with DP. Behavioral studies showed that 20 mg/kg of EB significantly alleviated pain in SNI mice and improved depressive‐like behaviors. Mechanism research indicated that EB downregulated the expression of EGFR and PTGS2, inhibited the activation of microglia and astrocytes, and reduced neuronal damage. Additionally, EB could upregulate the expression of synaptic proteins (PSD95, SYN1, and BDNF) in the hippocampus.

Conclusion: EB alleviates neuroinflammation by reducing EGFR and PTGS2 protein expression, modulates synaptic plasticity, and improves pain‐depression comorbidity. EB may represent a promising therapeutic approach for pain‐related depression.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE81672 — at NCBI GEO; found in the text, “Acquisition and Target Validation of a…”
• uniprot.org/uniprot/o14757 — at UniProt; found in the resources table
• uniprot.org/uniprot/p00374 — at UniProt; found in the resources table
• uniprot.org/uniprot/p00533 — at UniProt; found in the resources table
• uniprot.org/uniprot/p03372 — at UniProt; found in the resources table
• uniprot.org/uniprot/p04035 — at UniProt; found in the resources table
• uniprot.org/uniprot/p05412 — at UniProt; found in the resources table
• uniprot.org/uniprot/p06401 — at UniProt; found in the resources table
• uniprot.org/uniprot/p08069 — at UniProt; found in the resources table
• uniprot.org/uniprot/p10275 — at UniProt; found in the resources table
• uniprot.org/uniprot/p11142 — at UniProt; found in the resources table
• uniprot.org/uniprot/p11511 — at UniProt; found in the resources table
• uniprot.org/uniprot/p12931 — at UniProt; found in the resources table
• uniprot.org/uniprot/p17252 — at UniProt; found in the resources table
• uniprot.org/uniprot/p20248 — at UniProt; found in the resources table
• uniprot.org/uniprot/p24941 — at UniProt; found in the resources table
• uniprot.org/uniprot/p29474 — at UniProt; found in the resources table
• uniprot.org/uniprot/p35354 — at UniProt; found in the resources table
• uniprot.org/uniprot/p37231 — at UniProt; found in the resources table
• uniprot.org/uniprot/p42574 — at UniProt; found in the resources table
• uniprot.org/uniprot/p45983 — at UniProt; found in the resources table
• uniprot.org/uniprot/q16539 — at UniProt; found in the resources table
• uniprot.org/uniprot/q92731 — at UniProt; found in the resources table
• uniprot.org/uniprotkb/p01584 — at UniProt; found in the resources table

Other data links

• ncbi.nlm.nih.gov/geo — NCBI; found in the text, “Acquisition and Target Validation of a…”

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 6 keywords, 11 MeSH terms, 2 funders, 54 references.

Cite

This paper

Yang, X., Jiang, F., Wu, Y., Chen, K., & Xiang, H. (2026). The Small Molecule Compound Eupalinolide B Ameliorates Depressive Behaviors and Neuropathic Pain in Mice With Spared Nerve Injury: Integrating Network Pharmacology, Molecular Docking, Bioinformatics, Molecular Dynamics Simulation and Experimental Verification. CNS neuroscience & therapeutics, 32(4), e70872. https://doi.org/10.1002/cns.70872

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