Research Studio of Integration of Traditional and Western Medicine, First Hospital, Peking University, Beijing, China.
Phytomedicine. 2012 Jan 15;19(2):122-9. doi: 10.1016/j.phymed.2011.08.003. Epub 2011 Sep 3.
Neuroinflammation plays an important role in several neurodegenerative diseases. In this study, we investigated the anti-inflammatory properties of modified Wu-Zi-Yan-Zong prescription (MWP), a traditional Chinese polyherbal formula, in primary cultured rat astrocytes treated with lipopolysaccharide (LPS). The results showed that MWP significantly inhibited release of nitric oxide (NO) and prostaglandin E (PGE), as well as expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in LPS-induced rat astrocytes. Mechanism study indicated that MWP significantly inhibited nuclear factor-kappa B (NF-κB) inflammatory signaling pathway through attenuating inhibitor of nuclear factor-κB (IκB) degradation and down-regulating IκB kinases (IKKs) phosphorylation level. Moreover, MWP also decreased c-Jun NH(2)-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) phosphorylation, which play an important role in the induction of proinflammatory gene expressions. At last, MWP protected neurons from LPS-activated astrocytes in neuron-astrocyte co-culture system. Taken together, our results suggest that MWP may act to suppress neuroinflammatory response in LPS-stimulated rat astrocytes via NF-κB and JNK/p38 MAPK signaling cascades, and MWP may be a useful agent for prevention and treatment of neuroinflammatory disease.
神经炎症在几种神经退行性疾病中起着重要作用。在这项研究中，我们研究了改良五子衍宗方（MWP），一种传统的中药复方，在脂多糖（LPS）处理的原代培养大鼠星形胶质细胞中的抗炎特性。结果表明，MWP 显著抑制了 LPS 诱导的大鼠星形胶质细胞中一氧化氮（NO）和前列腺素 E（PGE）的释放，以及诱导型一氧化氮合酶（iNOS）和环氧化酶（COX）-2 的表达。机制研究表明，MWP 通过抑制核因子-κB（NF-κB）抑制因子（IκB）的降解和下调 IκB 激酶（IKKs）的磷酸化水平，显著抑制 NF-κB 炎症信号通路。此外，MWP 还降低了 c-Jun NH2-末端激酶（JNK）/丝裂原激活蛋白激酶（MAPK）的磷酸化，这在诱导促炎基因表达中起着重要作用。最后，MWP 在神经元-星形胶质细胞共培养系统中保护神经元免受 LPS 激活的星形胶质细胞的侵害。总之，我们的结果表明，MWP 可能通过 NF-κB 和 JNK/p38 MAPK 信号通路抑制 LPS 刺激的大鼠星形胶质细胞中的神经炎症反应，MWP 可能是预防和治疗神经炎症性疾病的有用药物。
