Xuming Zhusan Decoction Attenuates Post-Stroke via Modulating TLR4/MYD88/NF-κB Pathway in Mice

Area of Science:

• Neuroscience
• Pharmacology
• Traditional Chinese Medicine

Background:

• Ischemic stroke triggers neuroinflammation, worsening brain damage.
• The Chinese medicine Xuming Zhusan (XMZS) shows potential for stroke treatment, but its mechanism is not fully understood.

Purpose of the Study:

• To investigate XMZS's effects on microglial-mediated neuroinflammation in ischemic stroke.
• To identify the molecular targets of XMZS in the context of neuroinflammation.

Main Methods:

• In vivo studies utilized a middle cerebral artery occlusion (MCAO) mouse model of cerebral ischemia-reperfusion injury.
• In vitro studies used primary microglia and cortical neurons subjected to oxygen-glucose deprivation/reoxygenation (OGD/R).
• Techniques included behavioral assessments, histology, Western blotting, co-immunoprecipitation, confocal microscopy, and ELISA to analyze the TLR4/MYD88/NF-κB pathway.

Main Results:

• High-dose XMZS improved neurological function, reduced infarct volume, and decreased brain edema in MCAO mice.
• XMZS suppressed microglial activation and lowered pro-inflammatory cytokines (IL-1β, IL-6, TNF-α).
• XMZS downregulated key pathway components: TLR4, MYD88, and phosphorylated p65, while enhancing neuronal viability.

Conclusions:

• XMZS demonstrates neuroprotective effects against cerebral ischemia-reperfusion injury.
• XMZS attenuates neuroinflammation by modulating the TLR4/MYD88/NF-κB signaling pathway.
• XMZS treatment of microglia enhances neuronal survival, suggesting a protective role in the neuroinflammatory cascade.