Department of Neurology, Lanzhou University Second Hospital, Lanzhou, China.
Institute of Genetics, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
Clin Exp Pharmacol Physiol. 2023 Aug;50(8):647-663. doi: 10.1111/1440-1681.13784. Epub 2023 Jun 12.
Ligustilide, a natural phthalide mainly derived from chuanxiong rhizomes and Angelica Sinensis roots, possesses anti-inflammatory activity, particularly in the context of the nervous system. However, its application is limited because of its unstable chemical properties. To overcome this limitation, ligusticum cycloprolactam (LIGc) was synthesized through structural modification of ligustilide. In this study, we combined network pharmacological methods with experimental verification to investigate the anti-neuroinflammatory effects and mechanisms of ligustilide and LIGc. Based on our network pharmacology analysis, we identified four key targets of ligustilide involved in exerting an anti-inflammatory effect, with the nuclear factor (NF)-κB signal pathway suggested as the main signalling pathway. To verify these results, we examined the expression of inflammatory cytokines and inflammation-related proteins, analysed the phosphorylation level of NF-κB, inhibitor of κBα (IκBα) and inhibitor of κB kinase α and β (IKKα+β), and evaluated the effect of BV2 cell-conditioned medium on HT22 cells in vitro. Our results, demonstrate for the first time that LIGc can downregulate the activation of the NF-κB signal pathway in BV2 cells induced by lipopolysaccharide, suppress the production of inflammatory cytokines and reduce nerve injury in HT22 cells mediated by BV2 cells. These findings suggest that LIGc inhibits the neuroinflammatory response mediated by BV2 cells, providing strong scientific support for the development of anti-inflammatory drugs based on natural ligustilide or its derivatives. However, there are some limitations to our current study. In the future, further experiments using in vivo models may provide additional evidence to support our findings.
藁本内酯，一种主要从川芎根茎和当归根中提取的天然苯酞，具有抗炎活性，尤其是在神经系统方面。然而，由于其化学性质不稳定，其应用受到限制。为了克服这一限制，通过对藁本内酯进行结构修饰合成了川芎环肽（LIGc）。在这项研究中，我们结合网络药理学方法和实验验证来研究藁本内酯和 LIGc 的抗炎作用及其机制。基于我们的网络药理学分析，我们确定了藁本内酯发挥抗炎作用的四个关键靶点，其中核因子（NF）-κB 信号通路被认为是主要的信号通路。为了验证这些结果，我们检测了炎症细胞因子和炎症相关蛋白的表达，分析了 NF-κB、κB 抑制物α（IκBα）和κB 激酶α和β（IKKα+β）的磷酸化水平，并评估了 BV2 细胞条件培养基对体外 HT22 细胞的影响。我们的结果首次表明，LIGc 可以下调脂多糖诱导的 BV2 细胞中 NF-κB 信号通路的激活，抑制炎症细胞因子的产生，并减轻由 BV2 细胞介导的 HT22 细胞的神经损伤。这些发现表明，LIGc 抑制由 BV2 细胞介导的神经炎症反应，为基于天然藁本内酯或其衍生物开发抗炎药物提供了强有力的科学支持。然而，我们目前的研究存在一些局限性。在未来，使用体内模型的进一步实验可能会提供额外的证据来支持我们的发现。
