Berberine Protects Against NLRP3 Inflammasome via Ameliorating Autophagic Impairment in MPTP-Induced Parkinson's Disease Model.
Berberine Protects Against NLRP3 Inflammasome via Ameliorating Autophagic Impairment in MPTP-Induced Parkinson's Disease Model.
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小檗碱通过改善 MPTP 诱导的帕金森病模型中的自噬损伤来预防 NLRP3 炎症小体
DOI：
10.3389/fphar.2020.618787
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发表时间：
2020
影响因子：
5.6
通讯作者：
Lu L
中科院分区：
文献类型：
--
作者：
Huang S;Liu H;Lin Y;Liu M;Li Y;Mao H;Zhang Z;Zhang Y;Ye P;Ding L;Zhu Z;Yang X;Chen C;Zhu X;Huang X;Guo W;Xu P;Lu L
NLR家族pyrin domain containing 3（NLRP 3）炎性小体在帕金森病（PD）的炎症过程中受到自噬的调控并被激活。小檗碱（BBR）被广泛研究，在促进抗炎反应中发挥重要作用，介导自噬活性。然而，小檗碱对PD中NLRP 3炎性小体的影响及其潜在机制尚不清楚。因此，在本研究中，我们研究了BBR对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的PD小鼠的影响，通过评估其行为学变化、多巴胺（DA）能神经元损失、神经炎症、NLRP 3炎性小体和自噬活性。BBR还应用于用1-甲基-4-苯基-吡啶（MPP+）处理的BV2细胞中。应用自噬抑制剂3-甲基腺嘌呤（3-MA）在体内和体外阻断自噬活性。在我们的体内研究中，与MPTP组相比，MPTP + BBR组中的小鼠显示出行为障碍的显著改善，神经毒性和NLRP 3相关的神经炎症的减轻，黑质（SN）中自噬过程的增强。与MPP+组相比，BBR可通过增强自噬活性，降低NLRP 3炎性小体的表达，包括NLRP 3、PYD和CARD结构域（PYCARD）、半胱天冬酶1（CASP 1）和成熟白细胞介素1 β（IL 1B）的表达。此外，BBR处理增加MPP+处理的BV2细胞中自噬体的形成。总之，我们的数据表明，BBR阻止NLRP 3炎性小体激活并恢复自噬活性，以保护DA神经元免受体内和体外变性，这表明BBR可能是治疗PD的潜在治疗剂。
The NLR family pyrin domain containing 3 (NLRP3) inflammasome was reported to be regulated by autophagy and activated during inflammatory procession of Parkinson’s disease (PD). Berberine (BBR) is well-studied to play an important role in promoting anti-inflammatory response to mediate the autophagy activity. However, the effect of Berberine on NLRP3 inflammasome in PD and its potential mechanisms remain unclear. Hence, in this study, we investigated the effects of BBR on 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice, by evaluating their behavioral changes, dopaminergic (DA) neurons loss, neuroinflammation, NLRP3 inflammasome and autophagic activity. BBR was also applied in BV2 cells treated with 1-methyl-4-pehnyl-pyridine (MPP+). The autophagy inhibitor 3-Methyladenine (3-MA) was administrated to block autophagy activity both in vivo and in vitro. In our in vivo studies, compared to MPTP group, mice in MPTP + BBR group showed significant amelioration of behavioral disorders, mitigation of neurotoxicity and NLRP3-associated neuroinflammation, enhancement of the autophagic process in substantia nigra (SN). In vitro, compared to MPP+ group, BBR significantly decreased the level of NLRP3 inflammasome including the expressions of NLRP3, PYD and CARD domain containing (PYCARD), cleaved caspase 1 (CASP1), and mature interleukin 1 beta (IL1B), via enhancing autophagic activity. Furthermore, BBR treatment increased the formation of autophagosomes in MPP+-treated BV2 cells. Taken together, our data indicated that BBR prevents NLRP3 inflammasome activation and restores autophagic activity to protect DA neurons against degeneration in vivo and in vitro, suggesting that BBR may be a potential therapeutic to treat PD.
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影响因子：
11
作者：
Kim HJ;Cho MH;Shim WH;Kim JK;Jeon EY;Kim DH;Yoon SY
通讯作者：
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影响因子：
10.3
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
5.5
作者：
Liu, Hui;You, Leiming;Hao, Yu
通讯作者：
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