Background: Acute spinal cord injury (SCI) leads to permanent disabilities. This study evaluated the neuroprotective effect of puerarin, a natural extract, in a rat model of SCI. Methods: Acute SCI models were established in rats using a modified Allen's method. Locomotor function was evaluated using the BBB test. The histological changes in the spinal cord were observed by H&E staining. Neuron survival and glial cells activation were evaluated by immunostaining. ELISA and realtime PCR were used to measure secretion and gene expression of cytokines. TUNEL staining was used to examine cell apoptosis and western blot analysis was used to detect protein expression. Results: Puerarin significantly increased BBB score in SCI rats, attenuated histological injury of spinal cord, decreased neuron loss, inhibited glial cells activation, alleviated inflammation, and inhibited cell apoptosis in the injured spinal cords. In addition, the downregulated PI3K and phospho-Akt protein expression were restored by puerarin. Conclusion: Puerarin accelerated locomotor function recovery and tissue repair of SCI rats, which is associated with its neuroprotection, glial cell activation suppression, anti-inflammatory and anti-apoptosis effects. These effects may be associated with the activation of PI3K/Akt signaling pathway.
Our previous studies demonstrated that the multifunctional agent TBN, a derivative of tetramethylpyrazine armed with a nitrone moiety, displayed high therapeutic efficacy in experimental ischemic stroke models. However, its molecular mechanisms of action underlying the neuroprotective effect need further exploration. In the present study, we found that TBN had significant activities scavenging free radicals such as OH, O and ONOO, inhibiting Ca overload, maintaining mitochondrial function and preventing neuronal damage in primary cortical cultures. Further, TBN was effective in reducing brain infarction and ameliorating impairment of behavioral functions in the permanent middle cerebral artery occlusion (p-MCAo) rat model. TBN down-regulated the expression of pro-apoptotic factors Bax, while up-regulated the expression of anti-apoptotic factor Bcl-2 and increased the expression of pro-survival factors including p-Akt and p-GSK3β in the peri-infarct cortex of p-MCAo rats. In addition, LY-294002 (a PI3K inhibitor) and MK2206 (an Akt inhibitor) significantly blocked the protective effect of TBN against OGD-induced death of cortical neurons. Taken together, the multifunctional mechanisms including scavenging free radicals, blocking calcium overload, maintaining mitochondrial function and activating the PI3K/Akt/p-GSK3β cell survival pathway were possibly involved in the neuroprotective effects of TBN, making it a promising clinical candidate for the treatment of ischemic stroke.
Punicalagin, a bioactive ellagitannin isolated from pomegranate, has been reported to have anti-inflammatory property. In the present study, we analyzed the role of punicalagin against acute respiratory distress syndrome (ARDS) induced by lipopolysaccharide (LPS) in mice. Male BALB/c mice with ARDS, induced by intranasal instillation of LPS, were treated with punicalagin 1 h prior to LPS exposure. The effects of punicalagin on pro-inflammatory cytokines, myeloperoxidase activity, nuclear factor kappa B (NF-κB) activation, and the histopathological changes were evaluated. The results showed that punicalagin treatment attenuated LPS-induced lung edema, elevating TNF-α, IL-6, and IL-1β levels in the bronchoalveolar lavage fluid (BALF). Meanwhile, punicalagin significantly inhibited LPS-induced increases in the macrophage and neutrophil infiltration of lung tissues and myeloperoxidase activity. Furthermore, punicalagin inhibits Toll-like receptor 4 (TLR4) expression and NF-κB activation induced by LPS. In conclusion, this is the first study to demonstrate that punicalagin protects against LPS-induced ARDS in mice. The underlying mechanisms may include inhibition of TLR4-mediated NF-κB signaling pathways.
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