Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Guangdong Pharmaceutical University, Guangzhou 510006, China.
Int Immunopharmacol. 2017 Sep;50:38-47. doi: 10.1016/j.intimp.2017.06.007. Epub 2017 Jun 15.
Baicalein, a major bioactive flavone constituent isolated from Scutellaria baicalensis Georgi, has been shown to be neuroprotective in several Parkinson's disease (PD) animal models. Since neuroinflammation has been known to play a critical role in the pathogenesis of PD, potential explanation for the neuroprotective action of anti-PD compounds involves among others reduced inflammation. Our study investigated that one of the mechanisms of protection afforded by baicalein in rotenone-induced parkinsonian rats was associated with anti-inflammatory action and explored its underlying mechanism in vivo and in vitro. The results showed that baicalein treatment improved motor impairments, attenuated brain damage, suppressed the production of proinflammatory cytokines (tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6)), modulated the astrocytes and microglia activation, and blocked the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signals in rotenone-induced rats of PD. Furthermore, treatment of baicalein prominently suppressed the generation of nitric oxide (NO) and the expression of inducible NO synthase (iNOS) protein by blocking LPS-induced IκBα phosphorylation and NF-κB translocation, and downregulated the Toll-like receptor 4 (TLR4) which functions in the upstream of NF-κB signal in the activated BV microglia. In conclusion, our studies suggest that baicalein may be effective in the treatment of PD through anti-neuroinflammation.
黄芩素是从黄芩中分离得到的主要生物活性黄酮类成分，已被证明在几种帕金森病 (PD) 动物模型中具有神经保护作用。由于神经炎症已被认为在 PD 的发病机制中起关键作用，因此抗 PD 化合物的神经保护作用的潜在解释涉及减少炎症等。我们的研究调查了黄芩素在鱼藤酮诱导的帕金森病大鼠中提供的保护机制之一与抗炎作用有关，并在体内和体外探索了其潜在机制。结果表明，黄芩素治疗可改善运动障碍，减轻脑损伤，抑制促炎细胞因子（肿瘤坏死因子 α (TNF-α) 和白细胞介素 6 (IL-6)）的产生，调节星形胶质细胞和小胶质细胞的激活，并阻断核因子-κB (NF-κB) 和丝裂原激活蛋白激酶 (MAPK) 在鱼藤酮诱导的 PD 大鼠中的信号转导。此外，黄芩素通过阻断 LPS 诱导的 IκBα 磷酸化和 NF-κB 易位，显著抑制一氧化氮 (NO) 的产生和诱导型一氧化氮合酶 (iNOS) 蛋白的表达，从而抑制 TLR4 的产生，TLR4 在 NF-κB 信号的上游在激活的 BV 小胶质细胞中起作用。总之，我们的研究表明，黄芩素通过抗神经炎症可能对 PD 的治疗有效。
