Fuwai Hospital, State Key Laboratory of Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Changping District Hospital of Traditional Chinese Medicine, Beijing, China; Graduate School of China Academy of Chinese Medical Sciences, Beijing, China.
Biochem Biophys Res Commun. 2023 Oct 15;677:38-44. doi: 10.1016/j.bbrc.2023.07.059. Epub 2023 Aug 1.
Myocardial fibrosis (MF) is the manifestation of a variety of cardiovascular diseases. Salidroside (SAL) has been proved to have a certain effect on anti-fibrosis in various organs. However, the mechanism of SAL in the treatment of MF remains unclear. Network pharmacology showed that there were 1228 SAL-related target genes and 2793 MF-related target genes. The intersection of these genes resulted in 271 drug-disease interactions, and 15 core active targets were filtered from protein-protein interaction mapping. The top 20 Gene ontology biological processes analysis showed that the involved processes were close to the pathogenesis of MF. Among the top 20 enriched KEGG pathways, Wnt/β-catenin and TGF-β1/Smad3 signaling pathways were identified. In vivo, MI rats exhibited thinning of the myocardial region and the formation of fibrous scars, the expression of smad3 and β-catenin were increased. After SAL treatment, there was a significant reduction in collagen area and a decrease in the ratio of collagen type I to type III. The expression of smad3 and β-catenin was suppressed and positively correlated with the dosage of SAL. SAL may contribute to the progression of MF through the TGF-β1/Smad3 and Wnt/β-catenin signaling pathways.
心肌纤维化（MF）是多种心血管疾病的表现。红景天苷（SAL）已被证明在各种器官的抗纤维化方面具有一定的作用。然而，SAL 治疗 MF 的机制尚不清楚。网络药理学显示，有 1228 个与 SAL 相关的靶基因和 2793 个与 MF 相关的靶基因。这些基因的交集导致 271 种药物-疾病相互作用，并从蛋白质-蛋白质相互作用映射中筛选出 15 个核心活性靶标。GO 生物过程分析的前 20 个显示，所涉及的过程接近 MF 的发病机制。在 20 个富集的 KEGG 通路中，鉴定出 Wnt/β-catenin 和 TGF-β1/Smad3 信号通路。在体内，MI 大鼠表现出心肌区域变薄和纤维瘢痕形成，smad3 和 β-catenin 的表达增加。经 SAL 治疗后，胶原面积显著减少，I 型胶原与 III 型胶原的比例降低。smad3 和 β-catenin 的表达受到抑制，并与 SAL 的剂量呈正相关。SAL 可能通过 TGF-β1/Smad3 和 Wnt/β-catenin 信号通路促进 MF 的进展。
