Panaxadiol Attenuates Neuronal Oxidative Stress and Apoptosis in Cerebral Ischemia/Reperfusion Injury via Regulation of the JAK3/STAT3/HIF-1α Signaling Pathway.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101473265 Publication Model: Print Cited Medium: Internet ISSN: 1755-5949 (Electronic) Linking ISSN: 17555930 NLM ISO Abbreviation: CNS Neurosci Ther Subsets: MEDLINE

Original Publication: Oxford, UK : Wiley-Blackwell, c2008-

Ginsenosides*/pharmacology ; Oxidative Stress*/drug effects ; Reperfusion Injury*/drug therapy ; Reperfusion Injury*/metabolism ; Apoptosis*/drug effects ; Signal Transduction*/drug effects ; Hypoxia-Inducible Factor 1, alpha Subunit*/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit*/drug effects ; Neuroprotective Agents*/pharmacology ; STAT3 Transcription Factor*/metabolism ; STAT3 Transcription Factor*/drug effects ; Neurons*/drug effects ; Neurons*/metabolism; Animals ; Mice ; Male ; Mice, Inbred C57BL ; Brain Ischemia/drug therapy ; Brain Ischemia/metabolism ; Molecular Docking Simulation ; Infarction, Middle Cerebral Artery/drug therapy

Background: Cerebral ischemic stroke (CIS) is a debilitating neurological condition lacking specific treatments. Cerebral ischemia/reperfusion injury (CIRI) is a critical pathological process in CIS.
Purpose: This study aimed to explore the protective effects of panaxadiol (PD) against oxidative stress-induced neuronal apoptosis in CIS/CIRI and its underlying mechanisms.
Method: An MCAO mouse model was established to investigate the therapeutic effects of PD in vivo. Network pharmacology and molecular docking techniques were used to predict PD's anti-CIS targets. The protective effects of PD were further validated in vitro using oxygen-glucose deprivation/reoxygenation (OGD/R)-treated HT22 cells. Finally, core targets were verified through combined in vivo and in vitro experiments to elucidate the mechanisms of PD in treating CIS.
Result: PD exhibited significant neuroprotective activity, demonstrated by restoration of behavioral performance, reduced infarct volume, and decreased neuronal apoptosis in mice. Network pharmacology analysis identified 24 overlapping target genes between PD and CIS-related targets. The hub genes, PTGS2, SERPINE1, ICAM-1, STAT3, MMP3, HMOX1, and NOS3, were associated with the HIF-1α pathway, which may play a crucial role in PD's anti-CIS effects. Molecular docking confirmed the stable binding of PD to these hub genes. Both in vitro and in vivo experiments further confirmed that PD significantly mitigates neuronal apoptosis and oxidative stress induced by CIS/CIRI.
Conclusion: PD significantly counteracts CIS/CIRI by modulating the JAK3/STAT3/HIF-1α signaling pathway, making it a promising therapeutic agent for treating CIS/CIRI.
(© 2025 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

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ZY2023Q009 Research Project of Traditional Chinese Medicine in Hubei Provincial Administration of traditional Chinese Medicine; 2024AFB522 Hubei Provincial Natural Science Foundation Youth Project

Keywords: apoptosis; cerebral ischemic stroke; network pharmacology; oxidative stress; panaxadiol

0 (Ginsenosides)
0 (Hypoxia-Inducible Factor 1, alpha Subunit)
0 (Hif1a protein, mouse)
0 (Neuroprotective Agents)
0 (STAT3 Transcription Factor)
19666-76-3 (panaxadiol)
0 (Stat3 protein, mouse)

Date Created: 20250217 Date Completed: 20250217 Latest Revision: 20250219

20250219

PMC11831195

10.1111/cns.70233

39957706