Shutao Gao1, Tao Xu2, Hailong Guo3, Qiang Deng4, Chuanhui Xun5, Weidong Liang6, Weibin Sheng7. 1. Department of Spine Surgery, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, 830054, China. Electronic address: gaoshutoo@126.com. 2. Department of Spine Surgery, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, 830054, China. Electronic address: xt0005@sina.com. 3. Department of Spine Surgery, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, 830054, China. Electronic address: guohailong@tom.com. 4. Department of Spine Surgery, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, 830054, China. Electronic address: 1714250017@qq.com. 5. Department of Spine Surgery, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, 830054, China. Electronic address: xunchuanhui@126.com. 6. Department of Spine Surgery, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, 830054, China. Electronic address: guxiaoliang06@sina.com. 7. Department of Spine Surgery, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, 830054, China. Electronic address: wbsheng@vip.sina.com.
Abstract
AIMS: The activation of NLRP3 inflammasome, which initiates an inflammatory cascade and triggers inflammatory death, plays a crucial role in the pathogenesis of spinal cord injury (SCI). Echinacoside (ECH) is a phenylethanoid glycoside possessing prominent anti-inflammatory effects and various neuroprotective properties in the central nervous system, but the effect of ECH on SCI was rarely studied. Therefore, the purpose of this experiment was to look into the therapeutic effects of ECH on SCI and the underlying mechanisms. MAIN METHODS: Basso-Beattie-Bresnahan (BBB) locomotion scale, Nissl staining, and hematoxylin-eosin (HE) staining was employed to examine the therapeutic effects of ECH on SCI. In addition, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) in BV-2 cells stimulated with lipopolysaccharides and adenosine 5'-triphosphate were examined. The expression levels of proteins involving NLRP3 inflammasome-related pathway were measured. KEY FINDINGS: The in vivo experiment indicated that administration of ECH significantly enhanced the BBB scores, reduced the neuron loss, and ameliorated the tissue architecture after SCI. Additionally, ECH dramatically inhibited NLRP3 inflammasome activation in the rat SCI model. In vitro study indicated that ECH significantly reduced ROS level, improved the MMP, blocked activation of NF-κB, and inhibited the NLRP3 inflammasome signaling pathway. The effect of ECH on inhibition of NLRP3 inflammasome signaling pathway was partially governed by suppression of the generation of ROS and activation of NF-κB. SIGNIFICANCE: ECH can accelerate motor function recovery in rats following SCI by inhibiting NLRP3 inflammasome-related signaling pathway, suggesting that ECH may serve as a potential therapeutic agent for treating SCI.
AIMS: The activation of NLRP3 inflammasome, which initiates an inflammatory cascade and triggers inflammatory death, plays a crucial role in the pathogenesis of spinal cord injury (SCI). Echinacoside (ECH) is a phenylethanoid glycoside possessing prominent anti-inflammatory effects and various neuroprotective properties in the central nervous system, but the effect of ECH on SCI was rarely studied. Therefore, the purpose of this experiment was to look into the therapeutic effects of ECH on SCI and the underlying mechanisms. MAIN METHODS: Basso-Beattie-Bresnahan (BBB) locomotion scale, Nissl staining, and hematoxylin-eosin (HE) staining was employed to examine the therapeutic effects of ECH on SCI. In addition, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) in BV-2 cells stimulated with lipopolysaccharides and adenosine 5'-triphosphate were examined. The expression levels of proteins involving NLRP3 inflammasome-related pathway were measured. KEY FINDINGS: The in vivo experiment indicated that administration of ECH significantly enhanced the BBB scores, reduced the neuron loss, and ameliorated the tissue architecture after SCI. Additionally, ECH dramatically inhibited NLRP3 inflammasome activation in the ratSCI model. In vitro study indicated that ECH significantly reduced ROS level, improved the MMP, blocked activation of NF-κB, and inhibited the NLRP3 inflammasome signaling pathway. The effect of ECH on inhibition of NLRP3 inflammasome signaling pathway was partially governed by suppression of the generation of ROS and activation of NF-κB. SIGNIFICANCE: ECH can accelerate motor function recovery in rats following SCI by inhibiting NLRP3 inflammasome-related signaling pathway, suggesting that ECH may serve as a potential therapeutic agent for treating SCI.