肝纤维化是指多种因素引起的复杂炎症反应，是导致肝硬化甚至肝癌的已知原因。藏红花作为名贵药食同源草本植物，在世界范围内得到广泛应用。藏红花常用于治疗肝脏相关疾病，具有丰富的治疗和保健功效。治疗效果令人满意，但其机制尚不清楚。为了阐明这些问题，我们计划通过网络药理学分析结合体内验证实验来确定藏红花提取物预防和治疗肝纤维化的药理作用和机制。通过UPLC-Q-Exactive-MS分析，共鉴定出56种营养素和活性成分，并筛选其中9种来预测其肝纤维化的治疗靶点。然后，应用网络药理学分析确定了藏红花提取物缓解肝纤维化的 321 个靶点。功能和通路富集分析表明，藏红花治疗肝纤维化的假定靶点主要涉及钙信号通路、HIF-1信号通路、内分泌抵抗、PI3K/Akt信号通路、脂质和动脉粥样硬化以及cAMP 信号通路。基于CCl4诱导的肝纤维化小鼠模型，我们通过实验证实藏红花提取物可以减轻肝纤维化进展过程中的严重程度和病理变化。 RT-PCR和Western blotting分析证实藏红花治疗可以阻止CCl4诱导的HIF-1α、VEGFA、AKT和PI3K上调，表明藏红花可能调节AKT/HIF-1α/VEGF并减轻肝纤维化。

Liver fibrosis refers to a complex inflammatory response caused by multiple factors, which is a known cause of liver cirrhosis and even liver cancer. As a valuable medicine food homology herb, saffron has been widely used in the world. Saffron is commonly used in liver-related diseases and has rich therapeutic and health benefits. The therapeutic effect is satisfactory, but its mechanism is still unclear. In order to clarify these problems, we planned to determine the pharmacological effects and mechanisms of saffron extract in preventing and treating liver fibrosis through network pharmacology analysis combined with in vivo validation experiments. Through UPLC-Q-Exactive-MS analysis, a total of fifty-six nutrients and active ingredients were identified, and nine of them were screened to predict their therapeutic targets for liver fibrosis. Then, network pharmacology analysis was applied to identify 321 targets for saffron extract to alleviate liver fibrosis. Functional and pathway enrichment analysis showed that the putative targets of saffron for the treatment of hepatic fibrosis are mainly involved in the calcium signaling pathway, the HIF-1 signaling pathway, endocrine resistance, the PI3K/Akt signaling pathway, lipid and atherosclerosis, and the cAMP signaling pathway. Based on the CCl4-induced liver fibrosis mice model, we experimentally confirmed that saffron extract can alleviate the severity and pathological changes during the progression of liver fibrosis. RT-PCR and Western blotting analysis confirmed that saffron treatment can prevent the CCl4-induced upregulation of HIF-1α, VEGFA, AKT, and PI3K, suggesting that saffron may regulate AKT/HIF-1α/VEGF and alleviate liver fibrosis.