Cistanche deserticola polysaccharide alleviates spinal cord injury in mice by inhibiting NLRP3 inflammasome activation
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BACKGROUND/OBJECTIVES: Spinal cord injury (SCI) is a severe trauma in the central nervous system (CNS) that not only affects human health but also imposes a significant burden on families. Several herbal extracts have been ascertained to regulate SCI progression. Cistanche deserticola polysaccharide (CDP), extracted from C. deserticola, exhibits beneficial effects in a variety of diseases. However, the regulatory roles and associated pathways of CDP in the SCI progression remains unclear. MATERIALS/METHODS: The SCI animal model was successfully established. The Basso- Beattie-Bresnahan scores were determined through locomotion recovery assessment. Histopathological changes in spinal cord tissues were confirmed through hematoxylin eosin staining, while the number of Nissl bodies in ventral horn of spinal cord was verified through Nissl staining. The levels of malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase were quantified using commercial assay kits. The expression of ionized calcium- binding adapter molecule 1 (Iba-1) or nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated through immunofluorescence assay, and the protein expressions were inspected through western blot analysis. RESULTS: CDP treatment significantly improved the histopathological damage of spinal cord tissues following SCI. Additionally, CDP alleviated oxidative stress in spinal cord tissue. It also alleviated microglia activation by reducing Iba-1 expression. Mechanistically, CDP triggered the Nrf2 signaling pathway, which in turn suppressed NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, as proved through rescue assays. CONCLUSION: CDP alleviates SCI in mice by inhibiting NLRP3 inflammasome activation via the Nrf2 pathway. This finding suggested that CDP may serve as a promising drug for ameliorating SCI.
Abstract
BACKGROUND/OBJECTIVES: Spinal cord injury (SCI) is a severe trauma in the central nervous system (CNS) that not only affects human health but also imposes a significant burden on families. Several herbal extracts have been ascertained to regulate SCI progression. Cistanche deserticola polysaccharide (CDP), extracted from C. deserticola, exhibits beneficial effects in a variety of diseases. However, the regulatory roles and associated pathways of CDP in the SCI progression remains unclear. MATERIALS/METHODS: The SCI animal model was successfully established. The Basso- Beattie-Bresnahan scores were determined through locomotion recovery assessment. Histopathological changes in spinal cord tissues were confirmed through hematoxylin eosin staining, while the number of Nissl bodies in ventral horn of spinal cord was verified through Nissl staining. The levels of malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase were quantified using commercial assay kits. The expression of ionized calcium- binding adapter molecule 1 (Iba-1) or nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated through immunofluorescence assay, and the protein expressions were inspected through western blot analysis. RESULTS: CDP treatment significantly improved the histopathological damage of spinal cord tissues following SCI. Additionally, CDP alleviated oxidative stress in spinal cord tissue. It also alleviated microglia activation by reducing Iba-1 expression. Mechanistically, CDP triggered the Nrf2 signaling pathway, which in turn suppressed NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, as proved through rescue assays. CONCLUSION: CDP alleviates SCI in mice by inhibiting NLRP3 inflammasome activation via the Nrf2 pathway. This finding suggested that CDP may serve as a promising drug for ameliorating SCI.