The Sixth People's Hospital of Nantong.
Biol Pharm Bull. 2023;46(7):929-938. doi: 10.1248/bpb.b23-00071.
Chlorogenic acid (CGA), derived from dicotyledons and ferns, has been demonstrated with anti-inflammatory, anti-bacterial, and free radical-scavenging effects and can be used to treat pulmonary fibrosis (PF). However, the specific mechanism by which CGA treats PF needs to be further investigated. In this study, in vivo experiment was firstly performed to evaluate the effects of CGA on epithelial-mesenchymal transition (EMT) and autophagy in bleomycin (BLM)-induced PF mice. Then, the effects of CGA on EMT and autophagy was assessed using transforming growth factor beta (TGF-β) 1-induced EMT model in vitro. Furthermore, autophagy inhibitor (3-methyladenine) was used to verify that the inhibitory mechanism of CGA on EMT was associated with activating autophagy. Our results found that 60 mg/kg of CGA treatment significantly ameliorated lung inflammation and fibrosis in mice with BLM-induced PF. Besides, CGA inhibited EMT and promoted autophagy in mice with PF. In vitro studies also demonstrated that 50 µM of CGA treatment inhibited EMT and induced autophagy related factors in TGF-β1-induced EMT cell model. Moreover, the inhibitory effect of CGA on autophagy and EMT in vitro was abolished after using autophagy inhibitor. In conclusion, CGA could inhibit EMT to treat BLM-induced PF in mice through, activating autophagy.
绿原酸（CGA）来源于双子叶植物和蕨类植物，具有抗炎、抗菌和清除自由基的作用，可用于治疗肺纤维化（PF）。然而，CGA 治疗 PF 的具体机制仍需进一步研究。在本研究中，首先进行了体内实验，评估 CGA 对博来霉素（BLM）诱导的 PF 小鼠上皮-间充质转化（EMT）和自噬的影响。然后，使用转化生长因子β（TGF-β）1诱导的 EMT 模型在体外评估 CGA 对 EMT 和自噬的影响。此外，使用自噬抑制剂（3-甲基腺嘌呤）验证 CGA 抑制 EMT 的抑制机制与激活自噬有关。我们的研究结果发现，60mg/kg 的 CGA 治疗可显著改善 BLM 诱导的 PF 小鼠的肺部炎症和纤维化。此外，CGA 抑制 EMT 并促进 PF 小鼠的自噬。体外研究还表明，50µM 的 CGA 处理可抑制 EMT 并诱导 TGF-β1 诱导的 EMT 细胞模型中的自噬相关因子。此外，在使用自噬抑制剂后，CGA 对自噬和 EMT 的体外抑制作用被消除。综上所述，CGA 可通过激活自噬抑制 EMT 来治疗 BLM 诱导的 PF 小鼠。
