Adverse Drug Reaction Monitoring Center, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, P. R. China.
Department of Pneumology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, P. R. China.
Biosci Biotechnol Biochem. 2020 Jun;84(6):1131-1138. doi: 10.1080/09168451.2020.1721263. Epub 2020 Feb 5.
As a respiratory disease with high morbidity and mortality, pulmonary fibrosis (PF) has been a serious threat to people's health. Hederagenin (HDG) is a pentacyclic triterpenoid saponin widely distributed in various plants. This study explored the role of HDG in Bleomycin (BLM)-induced PF and the molecular mechanism. The results showed that HDG reduced BLM-induced pulmonary dysfunction, pathological damage in a dose-dependent manner. Besides, HDG reduced BLM-induced collagen deposition by decreasing the levels of α-SMA, Collagen I and hydroxproline. Furthermore, HDG reduced the levels of inflammatory cytokines (TNF-α and IL-6), TGF-β1 and connective tissue growth factor (CTGF) in bronchoalveolar lavage fluid (BALF) or serum. Further mechanism analysis indicated that HDG inhibited the expression of Ras and phosphorylation of JNK and NFAT4 in a dose-dependent manner. However, the JNK pathway activator Anisomycin reversed this inhibitory effect. In conclusion, these findings suggest that HDG may be a potential target drug for PF therapy.
作为一种发病率和死亡率都很高的呼吸系统疾病，肺纤维化（PF）一直严重威胁着人们的健康。当药苷元（HDG）是一种广泛分布于各种植物中的五环三萜皂苷。本研究探讨了 HDG 在博来霉素（BLM）诱导的 PF 中的作用及其分子机制。结果表明，HDG 可降低 BLM 诱导的肺功能障碍和病理损伤，呈剂量依赖性。此外，HDG 通过降低 α-SMA、I 型胶原和羟脯氨酸的水平来减少 BLM 诱导的胶原沉积。此外，HDG 还降低了支气管肺泡灌洗液（BALF）或血清中炎症细胞因子（TNF-α和 IL-6）、TGF-β1 和结缔组织生长因子（CTGF）的水平。进一步的机制分析表明，HDG 可抑制 Ras 的表达和 JNK 及 NFAT4 的磷酸化，呈剂量依赖性。然而，JNK 通路激活剂 Anisomycin 逆转了这种抑制作用。综上所述，这些发现表明 HDG 可能是 PF 治疗的潜在靶向药物。
