Molecular Chinese Medicine Laboratory, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Neuropharmacology. 2011 May;60(6):823-31. doi: 10.1016/j.neuropharm.2010.12.002. Epub 2010 Dec 10.
Stroke is the third most common cause of death worldwide. Recent findings showed that the severity of cerebrovascular diseases including ischemic stroke correlates with inflammation mediated responses in the neural cells. During ischemia, inflammatory mediators including tumor necrosis factor-alpha (TNF-α) and nitric oxide are produced by microglia, which play a central role in the pathogenesis of the disease. Ligusticum chuanxiong (LCX) is a commonly used traditional Chinese medicine (TCM) for empiric treatment of cerebrovascular and cardiovascular diseases for many centuries. By applying a bioactivity-guided fractionation scheme, two compounds with inhibition on neuroinflammation were isolated from LCX. Using chromatographic and spectrometric methods, they were identified to be senkyunolide A and Z-ligustilide. They could inhibit the production of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells and human peripheral blood monocyte derived macrophages. In addition, both compounds protected Neuro-2a cells from neuroinflammatory toxicity induced by the conditioned culture media produced by LPS-stimulated BV-2 cells. The underlying mechanisms of action of senkyunolide A were further delineated. Its inhibitory effects were shown to be independent of the phosphorylation of mitogen-activated protein kinases (MAPK) and translocation of nuclear factor kappa B (NF-κB). However, senkyunolide A could increase the degradation of TNF-α mRNA and reduce its half life by 43%. In conclusion, bioactivity-guided fractionation is an effective way of isolating bioactive compounds from medicinal herbs. In addition, senkyunolide A and Z-ligustilide isolated from LCX may be considered as potential complementary drug candidates for treating inflammatory processes associated with cerebrovascular diseases.
中风是全球第三大致死原因。最近的研究结果表明，包括缺血性中风在内的脑血管疾病的严重程度与神经细胞中的炎症介导反应有关。在缺血期间，小胶质细胞产生炎症介质，包括肿瘤坏死因子-α（TNF-α）和一氧化氮，它们在疾病的发病机制中发挥核心作用。川芎（LCX）是一种常用于治疗脑血管和心血管疾病的传统中药（TCM），已有数百年的经验。通过应用生物活性导向的分级方案，从 LCX 中分离出两种具有神经炎症抑制作用的化合物。通过色谱和光谱方法，它们被鉴定为藁本内酯 A 和 Z-川芎内酯。它们可以抑制脂多糖（LPS）刺激的鼠 BV-2 小胶质细胞和人外周血单核细胞衍生的巨噬细胞中促炎介质的产生。此外，这两种化合物都能保护神经-2a 细胞免受 LPS 刺激的 BV-2 细胞产生的条件培养基诱导的神经炎症毒性。进一步阐明了藁本内酯 A 的作用机制。其抑制作用与丝裂原活化蛋白激酶（MAPK）的磷酸化和核因子 kappa B（NF-κB）的易位无关。然而，藁本内酯 A 可以通过增加 TNF-α mRNA 的降解并将其半衰期缩短 43%来减少其表达。总之，生物活性导向的分级是从草药中分离生物活性化合物的有效方法。此外，从 LCX 中分离出的藁本内酯 A 和 Z-川芎内酯可能被认为是治疗与脑血管疾病相关的炎症过程的潜在互补药物候选物。
