Wogonoside alleviates inflammation induced by traumatic spinal cord injury by suppressing NF-κB and NLRP3 inflammasome activation

Abstract

Abstract. Wogonoside possesses anti-oxidative, anti-inflammatory, anti-allergy and anti-tumor properties. The aim of the present study was to evaluate whether wogonoside alleviates spinal cord injury (SCI)-induced inflammation via nuclear factor (NF)-κB and nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation. Sprague-Dawley rats were positioned in the jaws of a calibrated aneurysm clip with a closing pressure of 55 g. The jaws were placed on the dorsal and ventral surfaces of the spinal cord and left in place for 1 min. SCI rats were treated with 12, 25 and 50 mg/kg wogonoside. Following this, the locomotor function was assessed using the Basso Beattie Bresnahan scale. The water content of the spinal cord was measured, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 levels were assessed and western blot analysis was performed to evaluate the expressions of NF-κB and NLRP3. Wogonoside was demonstrated to significantly ameliorate the SCI-induced reduction in Basso Beattie Bresnahan score (P<0.01) and significantly reduce the water content of the spinal cord in rats with SCI-induced inflammation (P<0.01). Results also indicated that treatment with wogonoside significantly reduced the levels of IL-1β, TNF-α and IL-6 in rats with SCI-induced inflammation (P<0.01), potentially via the phosphorylation of NF-κB inhibitor α. Furthermore, treatment with wogonoside inhibited the expressions of toll-like receptor 4, NLRP3 and caspase-1 protein in SCI model rats (P<0.01). In conclusion, the results of the present study suggest that wogonoside alleviates SCI-induced inflammation by suppressing NF-κB and NLRP3 inflammasome activation.

Targeting the NLRP3 inflammasome to attenuate spinal cord injury in mice

“…Based on previous study [ 16 ], we performed qPCR of markers of the M1 phenotype microglia/macrophage (inducible nitric oxide synthase, iNOS) [ 4 , 13 , 25 ] or M2 phenotype microglia/macrophage (arginase1, Arg1) [ 4 , 13 , 25 ] and calculated the ratio of Arg1/iNOS mRNA to analyze the change of microglia/macrophage polarization 3 days post injury. We found that BAY 11-7082 ( P < 0.05) or A438079 ( P < 0.01) increased the ratio of Arg1/iNOS mRNA (Fig.…”

“…Here, we demonstrated that NLRP3 inflammasome blockade with BAY 11-7082 or A438079 decreased the number of CD68-positive cells, indicating the suppression of microglia/macrophage activation. Moreover, we analyzed microglia/macrophage polarization through investigation of the ratio of Arg1/iNOS mRNA based on previous study [ 16 ]. BAY 11-7082 or A438079 increased the ratio of Arg1/iNOS mRNA in our study.…”

“…Moreover, NLRP3 is expressed primarily in neurons and to a lesser extent in microglia and astroglia [ 13 ]. The neuroprotection of dopamine D1 receptor agonist [ 12 ], stromal cell-derived factor-1 alpha [ 13 ], d -β-hydroxybutyrate [ 15 ], wogonoside [ 16 ], quercetin [ 51 ], and asiatic acid [ 52 ] against SCI presumably depend on the inhibition of NLRP3 inflammasome activation to suppress neuroinflammation. Here, we showed that the mRNA expression of NLRP3 immediately increased within the first 6 h, further rose until at day 3 and dropped at day 7 post injury.…”

“…d -β-Hydroxybutyrate relieved pain hypersensitivity and promoted functional recovery in mice with SCI, possibly through inhibition of NLRP3 inflammasome activation [ 15 ]. Wogonoside attenuates SCI-induced neuroinflammation by inhibiting NF-κB and NLRP3 inflammasome activation [ 16 ]. No studies have demonstrated the role of NLRP3 inflammasome and the effects of NLRP3 inflammasome inhibitors in a mouse model of SCI.…”

MCC950, a Selective Inhibitor of NLRP3 Inflammasome, Reduces the Inflammatory Response and Improves Neurological Outcomes in Mice Model of Spinal Cord Injury

“…There is post-SCI activation of NLRP3 inflammasome in an animal model involving microglia and spinal cord tissue (Grace et al, 2016;Jiang et al, 2016;Zendedel et al, 2016). Further, previous studies have reported means of reducing neuroinflammation and promoting functional recovery in SCI animals by suppressing NLRP3 inflammasome activity (Qian et al, 2017;Zhu et al, 2017). Jiang et al (2017) reported that suppression of NLRP3 inflammasome activity to control neuroinflammation using the small-molecule inhibitor BAY 11-7082 or A438079 could attenuate mitochondria damage, alleviate SCI, and improve neuronal function restoration in a mouse model of SCI.…”