Tabersonine Alleviates Cerebral Ischemia/Reperfusion Injury Partly via Repressing the SLC6A2/NF-κB Signalling Pathway

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Cerebral ischemia/reperfusion (I/R) injury poses a significant threat to neural health.
• Understanding the mechanisms of neuroprotection is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the neuroprotective effects of Tabersonine in cerebral I/R injury.
• To elucidate the underlying regulatory mechanisms involving solute carrier family 6 member 2 (SLC6A2) and the NF-κB pathway.

Main Methods:

• Utilized oxygen-glucose deprivation/reoxygenation (OGD/R) in neural cells and a MCAO/R rat model.
• Employed cell counting kit 8 (CCK8) assay, ELISA, flow cytometry, molecular docking, and Western blotting.
• Assessed cell viability, inflammatory cytokines, apoptosis, reactive oxygen species (ROS), and superoxide dismutase (SOD) levels.

Main Results:

• Tabersonine enhanced neural cell viability, reduced apoptosis, and decreased inflammatory cytokine release (IL-1β, IL-6, TNF-α) under OGD/R stress.
• Tabersonine lowered ROS levels and increased SOD expression, with SLC6A2 identified as a key target.
• Tabersonine inactivated the NF-κB pathway partially via SLC6A2, demonstrating efficacy in vivo with reduced brain edema and inflammation.

Conclusions:

• Tabersonine exhibits significant neuroprotective properties against cerebral I/R injury.
• The mechanism involves the inactivation of the NF-κB pathway mediated by SLC6A2.
• Tabersonine represents a potential therapeutic agent for stroke and related neurological conditions.