Karacoline is a compound found in the plant Aconitum kusnezoffii Reichb. Although Aconitum kusnezoffii Reichb is widely used for the treatment of pain, very few studies have been carried out on the use of karacoline due to its potential toxicity. In this study, we selected key matrix metalloproteinases (MMPs), collagen II, and aggrecan as targets due to their association with intervertebral disc degeneration (IDD). Using these targets, we then used network pharmacology to predict a series of molecules that might exert therapeutic effects on IDD. Of these molecules, karacoline was predicted to have the best effect. Tumor necrosis factor (TNF)-α is known to promote the degeneration of the extracellular matrix in IDD. We therefore applied different concentrations of karacoline (0, 1.25, or 12.88 μM) along with 100 ng/mL TNF-α to rat nucleus pulposus cells and found that karacoline reduced the expression of MMP-14 in IDD by inhibiting the nuclear factor (NF)-κB pathway, while collagen II and aggrecan expression was increased. This suggested that extracellular matrix degradation was inhibited by karacoline (P < 0.05). Our data therefore reveal a new clinical application of karacoline and provide support for the use of network pharmacology in predicting novel drugs.

Karacoline是在植物乌头（Aconitum kusnezoffii Reichb）中发现的化合物。虽然乌头乌头Reichb被广泛用于治疗疼痛，由于其潜在的毒性，很少有人对其使用karacoline进行过研究。在这项研究中，我们选择了关键基质金属蛋白酶（MMP），胶原蛋白II和聚集蛋白聚糖作为靶标，因为它们与椎间盘退变（IDD）相关。然后，使用这些靶标，我们使用网络药理学来预测一系列可能对IDD产生治疗作用的分子。在这些分子中，据推测，karacoline具有最佳效果。已知肿瘤坏死因子（TNF）-α促进IDD中细胞外基质的变性。因此，我们应用了不同浓度的盐酸考拉林（0、1.25或12）。88μM）与100 ng / mLTNF-α一起作用于大鼠髓核细胞，发现karacoline通过抑制核因子（NF）-κB途径降低了IDD中MMP-14的表达，同时增加了II型胶原和蛋白聚糖的表达。这表明karacoline抑制了细胞外基质的降解（P  <0.05）。因此，我们的数据揭示了karacoline的新临床应用，并为预测新药的网络药理学使用提供了支持。