Sodium houttuyfonate attenuates neurological defects after traumatic brain injury in mice via inhibiting NLRP3 inflammasomes. Issue 9 (17th August 2021)

• Record Type: Journal Article
• Authors: Yao, Xiaolong; Wang, Shengbo; Chen, Yingchun; Sheng, Liuqing; Li, Huanhuan; You, Huichao; Ye, Jianfeng; Zhang, Qing; Li, Jun
• Is Part Of: Journal of biochemical and molecular toxicology. Volume 35:Issue 9(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-17
• Subjects: HMGB1 -- IL4 -- NF‐κB -- NLRP3 inflammasome -- sodium houttuyfonate -- traumatic brain injury; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Toxicology -- Periodicals; 574
• DOI: 10.1002/jbt.22850
• Languages: English
• ISSNs: 1095-6670

Abstract

Abstract: Sodium houttuyfonate (SH) is a chemical compound synthesized by houttuynin and sodium bisulfite. As it has antinflammatory effects, SH has been widely used to treat autoimmune diseases, including post events following traumatic brain injury (TBI). Meanwhile, NOD‐like receptor with pyrin domain containing‐3 (NLRP3) inflammasomes in microglia may play a central role in TBI. But to date, the intracellular mechanisms involved in the anti‐inflammatory effects of SH in TBI remain unknown, especially whether regulating NLRP3. To gain an insight into this possibility, we conducted cell culture and biochemical studies on the effect of SH on NLRP3 inflammasome in microglia. The results showed that SH inhibited TLR4 and NLRP3 inflammasome activation in the microglia cell. In parallel, phosphorylation of ERK and NF‐κB p65, which play a key role in NLRP3 inflammasome formation, was decreased. Intraperitoneal injection of SH into TBI mice significantly reduced the modified neurological severity score (mNSS), as well as the degree of microglia apoptosis post‐controlled cortical impact (CCI). Immunohistochemistry, Western blot analysis, and reverse‐transcription polymerase chain reaction (RT‐PCR) revealed that SH markedly reduced NLRP3 inflammasome activation, TLR4 activity, phosphorylation of ERK and NF‐κB. Moreover, SH significantly inhibited microglia activation post‐CCI, but effectively promoted the astrocyte activation and angiopoiesis. Taken together, our research provides evidence that SH attenuated neurological deficits post TBI through inhibiting NLRP3 inflammasome activation, via influencing the TLR4/NF‐κB signaling pathway. These findings explain the intracellular mechanism of the anti‐inflammatory activity caused by SH treatment following TBI.