Department of Emergency, Huaihe Hospital, Henan University, Kaifeng, 475000, People's Republic of China.
Department of Cardiology, Huaihe Hospital, Henan University, Kaifeng, 475000, People's Republic of China.
Biochem Biophys Res Commun. 2018 Sep 10;503(3):1949-1954. doi: 10.1016/j.bbrc.2018.07.140. Epub 2018 Jul 30.
Glaucocalyxin A (GLA) is a natural ent-Kaurane diterpenoid that possesses cardioprotective effect. Recently, it has been reported that GLA inhibits liver and pulmonary fibrosis, whereas its role in cardiac fibrosis remains unknown. In the present study, we evaluated the effect of GLA on the pathogenesis of cardiac fibrosis in vitro. The results showed that GLA inhibited angiotensin II (Ang II)-induced proliferation and migration in cardiac fibroblasts (CFs). GLA reduced the expression of alpha-smooth muscle actin (α-SMA) in Ang II-induced CFs, suggesting that GLA prevented the differentiation of CFs to myofibroblasts. Furthermore, the production of extracellular matrix (ECM) components including type I collagen (Col-I) and fibronectin, as well as the matrix metalloproteinases (MMPs) including MMP-2 and MMP-9 were reduced by GLA in Ang II-induced CFs. In addition, GLA prevented the Ang II-induced activation of transforming growth factor beta 1 (TGF-β1)/Smad3 pathway in CFs. Collectively, our results demonstrated that GLA acted as an anti-fibrotic agent in cardiac fibrosis, which might be mediated by the regulation of TGF-β1/Smad3 pathway. GLA might be an attractive candidate for improving the prognosis of acute myocardial infarction (AMI) by controlling the cardiac fibrosis.
白杨素 A（GLA）是一种天然的 ent-Kaurane 二萜，具有心脏保护作用。最近有报道称，GLA 可抑制肝肺纤维化，但其在心脏纤维化中的作用尚不清楚。在本研究中，我们评估了 GLA 对心脏纤维化发病机制的影响。结果表明，GLA 抑制了血管紧张素 II（Ang II）诱导的心肌成纤维细胞（CFs）的增殖和迁移。GLA 降低了 Ang II 诱导的 CFs 中α-平滑肌肌动蛋白（α-SMA）的表达，表明 GLA 阻止了 CFs 向肌成纤维细胞的分化。此外，GLA 减少了 Ang II 诱导的 CFs 中细胞外基质（ECM）成分包括 I 型胶原（Col-I）和纤维连接蛋白的产生，以及基质金属蛋白酶（MMPs）包括 MMP-2 和 MMP-9 的产生。此外，GLA 可预防 Ang II 诱导的 CFs 中转化生长因子β1（TGF-β1）/Smad3 通路的激活。综上所述，我们的研究结果表明，GLA 作为一种抗纤维化剂在心脏纤维化中发挥作用，这可能是通过调节 TGF-β1/Smad3 通路来实现的。GLA 可能是通过控制心脏纤维化来改善急性心肌梗死（AMI）预后的有吸引力的候选药物。
