Related Experiment Video
Updated: Jul 9, 2025
A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Orientin Reduces the Effects of Repeated Procedural Neonatal Pain in Adulthood: Network Pharmacology Analysis,
Dong-Dong Guo1, Hai-Yan Huang2, Hai-E Liu1
1Department of Anesthesiology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai 201102, China.
Insights
Orientin effectively reduces neonatal pain and associated hyperalgesia and cognitive impairment in mice. This flavonoid targets the mitogen-activated protein kinase (MAPK) signaling pathway, offering a potential therapeutic strategy for neonatal pain.
Area of Science:
- Pharmacology
- Neuroscience
- Biochemistry
Background:
- Premature infants experience repeated procedural pain, leading to hyperalgesia and cognitive deficits later in life.
- Current treatments for neonatal pain are limited, necessitating the exploration of novel therapeutic agents.
- Orientin, a flavonoid, exhibits known pharmacological effects and is investigated for its potential in managing neonatal pain.
Purpose of the Study:
- To systematically investigate the effects of orientin on repeated procedural neonatal pain.
- To elucidate the underlying molecular mechanisms of orientin's action using network pharmacology and molecular docking.
- To validate the therapeutic potential of orientin through experimental studies in a mouse model.
Main Methods:
- Network pharmacology identified 286 proteins targeted by orientin and involved in neonatal pain.
- Protein-protein interaction network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses explored mechanisms.
- Molecular docking assessed orientin's binding affinity to key proteins; experimental validation used a mouse model of neonatal pain and cognitive tests.
Main Results:
- Orientin demonstrated significant inhibition of hyperalgesia in neonate and adult mice and ameliorated cognitive impairment in adults.
- The mitogen-activated protein kinase (MAPK) signaling pathway was identified as a key mechanism via KEGG analysis.
- Orientin reduced phosphorylated MAPK1 (p-ERK) levels in the hippocampus and spinal dorsal horn, indicating pathway modulation.
Conclusions:
- Orientin effectively alleviates neonatal pain, hyperalgesia, and associated cognitive impairment.
- The therapeutic effects of orientin are mediated through the modulation of the MAPK signaling pathway.
- Orientin presents a promising therapeutic candidate for managing neonatal pain and its long-term consequences.
Background:
Premature infants often undergo painful procedures and consequently experience repeated procedural neonatal pain. This can elicit hyperalgesia and cognitive impairment in adulthood. Treatments for neonatal pain are limited. Orientin is a flavonoid C-glycoside that has repeatedly been shown to have pharmacological effects in the past decades. The aim of this study was to systematically explore the effect of orientin on repeated procedural neonatal pain using network pharmacology, molecular docking analysis, and experimental validation.
Methods:
Several compound-protein databases and disease-protein databases were employed to identify proteins that were both predicted targets of orientin and involved in neonatal pain. A protein-protein interaction (PPI) network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential mechanism of action. Molecular docking analysis was employed to calculate the binding energy and visualize the interactions between orientin and potential target proteins. Finally, a mouse model of repeated procedural neonatal pain was established and orientin was administered for 6 days. The mechanical and thermal pain thresholds were assessed in neonates and adult mice. A Morris water maze was employed to investigate cognitive impairment in adult mice.
Results:
A total of 286 proteins that were both predicted targets of orientin and involved in neonatal pain were identified. The hub proteins were SRC, HSP90AA1, MAPK1, RHOA, EGFR, AKT1, PTPN11, ESR1, RXRA, and HRAS. GO analysis indicated that the primary biological process (BP), molecular function (MF), and cellular component (CC) were protein phosphorylation, protein kinase activity, and vesicle lumen, respectively. KEGG analysis revealed that the mitogen-activated protein kinase (MAPK) signaling pathway may be the key to the mechanism of action. Molecular docking analysis showed the high binding affinities of orientin for MAPK1, MAPK8, and MAPK14. In mice, orientin inhibited the hyperalgesia in the pain threshold tests in neonates and adult mice and cognitive impairment in adult mice. Immunofluorescence showed that phosphorylated MAPK1 (p-ERK) protein levels in the hippocampus and spinal dorsal horn were downregulated by orientin.
Conclusion:
The findings suggested that orientin alleviates neonatal pain, and the MAPK signaling pathway is involved.
