Rosmarinic acid attenuates inflammatory responses through inhibiting HMGB1/TLR4/NF-κB signaling pathway in a mouse model of Parkinson's disease
Rosmarinic acid attenuates inflammatory responses through inhibiting HMGB1/TLR4/NF-κB signaling pathway in a mouse model of Parkinson's disease
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DOI：
10.1016/j.lfs.2019.03.030
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发表时间：
2019-04-15
期刊：
影响因子：
6.1
通讯作者：
Zhang, Lixin
中科院分区：
文献类型：
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作者：
Lv, Runxiao;Du, Lili;Zhang, Lixin
炎症有助于PD患者和动物模型的病理过程。迷迭香酸（RA）已被证明可以保护PD模型中的神经元。本研究旨在评价RA对PD的抗炎作用并揭示其可能的药理机制。采用1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）腹腔注射建立小鼠PD模型。采用1-甲基-4-苯基吡啶（MPP+）和α-突触核蛋白（alpha-synuclein，alpha-synuclein）诱导BV-2细胞建立PD模型。结果表明，RA剂量依赖性地改善PD小鼠的运动功能，增加酪氨酸羟化酶阳性细胞的数量，减少促炎细胞因子的产生，并抑制腹侧中脑小胶质细胞的激活。在细胞研究中，RA还减少MPP+或α-突触核蛋白诱导的促炎细胞因子的分泌。此外，RA治疗下调HMGB 1，TLR 4和Myd 88的表达水平，并抑制NF-κ B B核表达在PD动物和细胞模型。提示RA可能通过抑制HMGB 1/TLR 4/NF-κ B信号通路减轻炎症反应，这可能是其抗PD作用的机制之一。
Inflammation contributes to the pathological processes in patients and animal models of PD. Rosmarinic acid (RA) has been demonstrated to protect neurons in PD models. The present study aimed to evaluate the anti-inflammatory effect of RA on PD and reveal possible pharmacological mechanisms. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) was injected to mice to establish PD model in vivo. BV-2 cells were exposed to 1-methyl-4-phenylpyridinium (MPP+) and alpha-synuclein to establish PD model in vitro. Results showed that treatment with RA dose-dependently improved motor function of PD mice, increased the number of tyrosine hydroxylase-positive cells, reduced production of pro-inflammatory cytokines, and inhibited microglia activation in ventral midbrain. In cell study, RA also decreased MPP+ or alpha-synuclein-induced secretion of pro-inflammatory cytokines. Furthermore, RA treatment downregulated the expression levels of HMGB1, TLR4 and Myd88 and inhibited NF-kappa B nuclear expression both in PD animal and cell models. These findings indicated that RA could attenuate inflammatory responses through suppressing HMGB1/TLR4/NF-kappa B signaling pathway, which may contribute to its anti-PD activity.