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

The study aimed to investigate the neuroprotective functions and the underlying regulatory mechanisms of Tabersonine in cerebral ischemia/reperfusion (I/R) injury. Oxygen-glucose deprivation/reoxygenation (OGD/R)-treated neural cells were used as a cell model under I/R context. Cell counting kit 8 (CCK8) assay and enzyme-linked immunosorbent assay (ELISA) were used to assess the cell viability and the release levels of inflammatory cytokines (interleukin-1β (IL-1β), IL-6 and tumour necrosis factor α (TNF-α)) of treated neural cells. The apoptotic proportions of treated neural cells were analysed by flow cytometry, and the intracellular levels of reactive oxygen species (ROS) and superoxide dismutase (SOD) were quantified by corresponding kits. In this study, molecular docking analysis identified solute carrier family 6 member 2 (SLC6A2) as a potential target of Tabersonine in cerebral infarction, demonstrating a high binding affinity of -7.4 kcal/mol. Tabersonine treatment increased neural cell viability, repressed apoptosis and reduced the release levels of IL-1β, IL-6 and TNF-α under OGD/R stress. Moreover, Tabersonine treatment reduced ROS levels and increased SOD expression in neural cells under OGD/R treatment. In contrast to the protective effect of SLC6A2 knockdown, its overexpression counteracted the neuroprotection conferred by Tabersonine. Tabersonine also inactivated the NF-κB pathway partially via SLC6A2. Furthermore, Tabersonine pretreatment demonstrated significant neuroprotective effects in MCAO/R rats, as evidenced by reduced brain edema and attenuated neural inflammation and apoptosis. In conclusion, Tabersonine can alleviate neural impairment in cerebral I/R injury partially by inactivating the NF-κB pathway through SLC6A2.