Tenuigenin protects dopaminergic neurons from inflammation via suppressing NLRP3 inflammasome activation in microglia
Abstract Background Emerging evidence indicates that nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome-induced inflammation plays a crucial role in the pathogenesis of Parkinson’s disease (PD). Thus, inhibition of NLRP3 inflammasome activation may offer a therapeutic benefit i...
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doaj-4d61adbd9e884c0896d41e137d651cf22020-11-24T21:40:07ZengBMCJournal of Neuroinflammation1742-20942017-12-0114111210.1186/s12974-017-1036-xTenuigenin protects dopaminergic neurons from inflammation via suppressing NLRP3 inflammasome activation in microgliaZheng Fan0Zhigang Liang1Hui Yang2Yuting Pan3Yan Zheng4Xiaomin Wang5Department of Pharmacology, School of Basic Medical Sciences, Capital Medical UniversityDepartment of Neurology, Yantai Yuhuangding Hospital Affiliated to Qingdao UniversityCore Facility Center, Capital Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Capital Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Capital Medical UniversityDepartment of Neurobiology, School of Basic Medical Sciences, Capital Medical UniversityAbstract Background Emerging evidence indicates that nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome-induced inflammation plays a crucial role in the pathogenesis of Parkinson’s disease (PD). Thus, inhibition of NLRP3 inflammasome activation may offer a therapeutic benefit in the treatment of PD. Tenuigenin, a major active component of Polygala tenuifolia, has been shown to have potential anti-inflammatory activity, but the underlying mechanisms remain obscure. Methods In the present study, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was established to explore the effect of tenuigenin on dopaminergic neurons in substantia nigra. We next activated NLRP3 inflammasome in both BV2 microglia cells and adult mice to investigate the mechanisms for the neuroprotective effect of tenuigenin. Results We demonstrated that treatment with tenuigenin increased striatal dopaminergic levels and improved motor impairment induced by MPTP. Also, tenuigenin significantly ameliorated the degeneration of dopaminergic neurons and inhibited NLRP3 inflammasome activation in substantia nigra of MPTP mouse model. We further found that tenuigenin reduced intracellular reactive oxygen species (ROS) production and suppressed NLRP3 inflammasome activation, subsequent caspase-1 cleavage, and interleukin-1β secretion in BV2 microglia cells. These data indicate that tenuigenin inhibits the activation of NLRP3 inflammasome via downregulating ROS. Correspondingly, in vivo data showed that tenuigenin attenuates microglia activation induced by lipopolysaccharide (LPS) in substantia nigra via suppressing NLRP3 inflammasome. Conclusions Our findings reveal that tenuigenin protects dopaminergic neurons from inflammation partly through inhibition of NLRP3 inflammasome activation in microglia, and suggest the promising clinical use of tenuigenin for PD therapy.http://link.springer.com/article/10.1186/s12974-017-1036-xParkinson’s diseaseTenuigeninNLRP3 inflammasomeMicrogliaInflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zheng Fan Zhigang Liang Hui Yang Yuting Pan Yan Zheng Xiaomin Wang |
spellingShingle |
Zheng Fan Zhigang Liang Hui Yang Yuting Pan Yan Zheng Xiaomin Wang Tenuigenin protects dopaminergic neurons from inflammation via suppressing NLRP3 inflammasome activation in microglia Journal of Neuroinflammation Parkinson’s disease Tenuigenin NLRP3 inflammasome Microglia Inflammation |
author_facet |
Zheng Fan Zhigang Liang Hui Yang Yuting Pan Yan Zheng Xiaomin Wang |
author_sort |
Zheng Fan |
title |
Tenuigenin protects dopaminergic neurons from inflammation via suppressing NLRP3 inflammasome activation in microglia |
title_short |
Tenuigenin protects dopaminergic neurons from inflammation via suppressing NLRP3 inflammasome activation in microglia |
title_full |
Tenuigenin protects dopaminergic neurons from inflammation via suppressing NLRP3 inflammasome activation in microglia |
title_fullStr |
Tenuigenin protects dopaminergic neurons from inflammation via suppressing NLRP3 inflammasome activation in microglia |
title_full_unstemmed |
Tenuigenin protects dopaminergic neurons from inflammation via suppressing NLRP3 inflammasome activation in microglia |
title_sort |
tenuigenin protects dopaminergic neurons from inflammation via suppressing nlrp3 inflammasome activation in microglia |
publisher |
BMC |
series |
Journal of Neuroinflammation |
issn |
1742-2094 |
publishDate |
2017-12-01 |
description |
Abstract Background Emerging evidence indicates that nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome-induced inflammation plays a crucial role in the pathogenesis of Parkinson’s disease (PD). Thus, inhibition of NLRP3 inflammasome activation may offer a therapeutic benefit in the treatment of PD. Tenuigenin, a major active component of Polygala tenuifolia, has been shown to have potential anti-inflammatory activity, but the underlying mechanisms remain obscure. Methods In the present study, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was established to explore the effect of tenuigenin on dopaminergic neurons in substantia nigra. We next activated NLRP3 inflammasome in both BV2 microglia cells and adult mice to investigate the mechanisms for the neuroprotective effect of tenuigenin. Results We demonstrated that treatment with tenuigenin increased striatal dopaminergic levels and improved motor impairment induced by MPTP. Also, tenuigenin significantly ameliorated the degeneration of dopaminergic neurons and inhibited NLRP3 inflammasome activation in substantia nigra of MPTP mouse model. We further found that tenuigenin reduced intracellular reactive oxygen species (ROS) production and suppressed NLRP3 inflammasome activation, subsequent caspase-1 cleavage, and interleukin-1β secretion in BV2 microglia cells. These data indicate that tenuigenin inhibits the activation of NLRP3 inflammasome via downregulating ROS. Correspondingly, in vivo data showed that tenuigenin attenuates microglia activation induced by lipopolysaccharide (LPS) in substantia nigra via suppressing NLRP3 inflammasome. Conclusions Our findings reveal that tenuigenin protects dopaminergic neurons from inflammation partly through inhibition of NLRP3 inflammasome activation in microglia, and suggest the promising clinical use of tenuigenin for PD therapy. |
topic |
Parkinson’s disease Tenuigenin NLRP3 inflammasome Microglia Inflammation |
url |
http://link.springer.com/article/10.1186/s12974-017-1036-x |
work_keys_str_mv |
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