Dataset Information

Neuroprotective Effect of Oridonin on Traumatic Brain Injury via Inhibiting NLRP3 Inflammasome in Experimental Mice.

ABSTRACT: NLRP3 inflammasome has been considered as an important contributor to inflammation and neuronal death after traumatic brain injury (TBI). Oridonin (Ori), the major active ingredient of Chinese herbal medicine Rabdosia rubescens, has been proved to be a covalent NLRP3 inhibitor with strong anti-inflammation activity. The purpose of this study was to investigate the effect of Ori on inflammation and brain injury induced by TBI. Adult male C57BL/6 mice were subjected to closed-head injury using Hall's weight-dropping method. Ori was injected directly intraperitoneally at a dose of 10 mg/kg within 30 min after TBI and injected once daily until the experiments ended. Our results showed that NLRP3 inflammasome was activated within 24 h post-TBI. The expression of NLRP3 inflammasome components (NLRP3, ASC, and caspase-1) was significantly decreased after treatment with Ori. Besides, the secretion of IL-1? and IL-18, downstream inflammatory factors of activated caspase-1, was reduced by Ori treatment. Importantly, Ori administration further protected the blood-brain barrier, alleviated brain edema, reduced cortical lesion volume, decreased cell death, and attenuated neurological deficits after TBI. Our findings indicate that NLRP3 inflammasome participated in the secondary injury after TBI and the application of Ori may provide neuroprotection via inhibiting NLRP3 inflammasome in animal models, suggesting that Ori might be a promising candidate for patients with TBI.

SUBMITTER: Yan C

PROVIDER: S-EPMC7691250 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neuroprotective Effect of Oridonin on Traumatic Brain Injury via Inhibiting NLRP3 Inflammasome in Experimental Mice.

Yan Chaolong C Yan Huiying H Mao Jiannan J Liu Yutong Y Xu Li L Zhao Hongting H Shen Jiaqi J Cao Yan Y Gao Yongyue Y Li Kuanyu K Jin Wei W

Frontiers in neuroscience 20201113

NLRP3 inflammasome has been considered as an important contributor to inflammation and neuronal death after traumatic brain injury (TBI). Oridonin (Ori), the major active ingredient of Chinese herbal medicine <i>Rabdosia rubescens</i>, has been proved to be a covalent NLRP3 inhibitor with strong anti-inflammation activity. The purpose of this study was to investigate the effect of Ori on inflammation and brain injury induced by TBI. Adult male C57BL/6 mice were subjected to closed-head injury us ...[more]

PMID: 33281541

Similar Datasets

Project description:Traumatic brain injuries (TBI) are an important public health challenge. In addition, subsequent events at TBI can compromise the quality of life of these patients. In fact, TBI is associated with several complications for both long and short term, some evidence shows how TBI is associated with a decline in cognitive functions such as the risk of developing dementia, cerebral atrophy, and Parkinson disease. After the direct damage from TBI, a key role in TBI injury is played by the inflammatory response and oxidative stress, that contributes to tissue damage and to neurodegenerative processes, typical of secondary injury, after TBI. Given the complex series of events that are involved after TBI injury, a multitarget pharmacological approach is needed. Artesunate is a more stable derivative of its precursor artemisin, a sesquiterpene lactone obtained from a Chinese plant Artemisia annua, a plant used for centuries in traditional Chinese medicine. artesunate has been shown to be a pluripotent agent with different pharmacological actions. therefore, in this experimental model of TBI we evaluated whether the treatment with artesunate at the dose of 30 mg\Kg, had an efficacy in reducing the neuroinflammatory process after TBI injury, and in inhibiting the NLRP3 inflammasome pathway, which plays a key role in the inflammatory process. We also assessed whether treatment with artesunate was able to exert a neuroprotective action by modulating the release of neurotrophic factors. our results show that artesunate was able to reduce the TBI-induced lesion, it also showed an anti-inflammatory action through the inhibition of Nf-kb, release of proinflammatory cytokines IL-1? and TNF-? and through the inhibition NLRP3 inflammasome complex, furthermore was able to reduce the activation of astrocytes and microglia (GFAP, Iba-1). Finally, our results show that the protective effects of artesunate also occur through the modulation of neurotrophic factors (BDNF, GDNF, NT-3) that play a key role in neuronal survival.

Dataset Information

Neuroprotective Effect of Oridonin on Traumatic Brain Injury via Inhibiting NLRP3 Inflammasome in Experimental Mice.

Publications

Neuroprotective Effect of Oridonin on Traumatic Brain Injury via Inhibiting NLRP3 Inflammasome in Experimental Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure