Alpha lipoic acid inhibits oxidative stress-induced apoptosis by modulating of Nrf2 signalling pathway after traumatic brain injury.

Alpha lipoic acid (ALA) is a powerful antioxidant which has been widely used in the treatment of different system diseases, such as cardiovascular and cerebrovascular diseases. But, there are few studies that refer to protective effects and potential mechanisms on traumatic brain injury (TBI). This study was carried out to investigate the neuroprotective effect following TBI and illuminate the underlying mechanism. Weight drop-injured model in rats was induced by weight-drop. ALA was administrated via intraperitoneal injection after TBI. Neurologic scores were examined following several tests. Neurological score was performed to measure behavioural outcomes. Nissl staining and TUNEL were performed to evaluate the neuronal apoptosis. Western blotting was engaged to analyse the protein content of the Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream protein factors, including hemeoxygenase-1 (HO-1) and quinine oxidoreductase-1 (NQO1). ALA treatment alleviated TBI-induced neuron cell apoptosis and improved neurobehavioural function by up-regulation of Nrf2 expression and its downstream protein factors after TBI. This study presents new perspective of the mechanisms responsible for the neuronal apoptosis of ALA, with possible involvement of Nrf2 pathway.

Sinomenine Protects against Early Brain Injury by Inhibiting Microglial Inflammatory Response via Nrf2-Dependent Pathway after Subarachnoid Hemorrhage.

Microglial activation and sustained inflammation plays an important role in the processes of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Sinomenine (SIN) has been demonstrated to have neuroprotective effects in the traumatic brain injury (TBI) model. However, the role of SIN in SAH-induced EBI and its latent mechanisms remain unclear. This study was carried out to explore the role of SIN on SAH-induced EBI and its effects on the microglial inflammatory response following SAH. In this study, a model of SAH in rats was established. Modified neurological severity scores (mNSS), encephaledema, and Nissl staining were employed to determine the effects of SIN. Western blot and immunofluorescence analysis were performed to evaluate nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Nrf2-related downstream proteins, including heme oxygenase-1 (HO-1) and quinine oxidoreductase-1 (NQO-1), were detected with immunohistochemistry analyses and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). Microglia activation and associated inflammatory factors, factor-kappa B (NF-κB), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), were assessed after SAH. The results showed that SIN administration improved neurobehavior function, and attenuated neural apoptosis and brain edema after SAH. In addition, SIN inhibited microglial action and the subsequent inflammatory response after SAH through the upregulated expression of HO-1 and NQO-1 via activation of the Nrf2 pathway. These results demonstrated that SIN supplementation provided protection against SAH-induced neuronal apoptosis by microglial inflammatory response regulation and possible involvement of the Nrf2 pathway.

Sinomenine reduces neuronal cell apoptosis in mice after traumatic brain injury via its effect on mitochondrial pathway.

BACKGROUND: Sinomenine (SIN) has been shown to have protective effects against brain damage following traumatic brain injury (TBI). However, the mechanisms and its role in these effects remain unclear. This study was conducted to investigate the potential mechanisms of the protective effects of SIN. METHODS: The weight-drop model of TBI in Institute of Cancer Research (ICR) mice were treated with SIN or a vehicle via intraperitoneal administration 30 min after TBI. All mice were euthanized 24 h after TBI and after neurological scoring, a series of tests were performed, including brain water content and neuronal cell death in the cerebral cortex. RESULTS: The level of cytochrome c (Cyt c), malondialdehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase 1 (SOD) were restored to some degree following the SIN treatment. The SIN treatment significantly decreased caspase-3 expression and reduced the number of positive cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and improved the survival of neuronal cells. Additionally, the pretreatment levels of MDA were restored, while Bax translocation to mitochondria and Cyt c release into the cytosol were reduced by the SIN treatment. CONCLUSION: SIN protected neuronal cells by protecting them against apoptosis via mechanisms that involve the mitochondria following TBI.