QiShenYiQi Pills® ameliorates ischemia/reperfusion-induced myocardial fibrosis involving RP S19-mediated TGFβ1/Smads signaling pathway.

Abstract

QiShenYiQi Pills (QSYQ) is a compound Chinese medicine widely used in China for treatment of cardiovascular disease. However, limited data are available regarding the anti-fibrotic role of QSYQ after ischemia/reperfusion (I/R) injury. This study aimed to investigate the effect of post-treatment with QSYQ on myocardial fibrosis after I/R-induced myocardium injury, and the role of different compounds of QSYQ, focusing especially on the involvement of chemokine ribosomal protein S19 (RP S19) dimer and monocyte migration. Male Sprague-Dawley rats were subjected to left anterior descending coronary artery occlusion for 30 min followed by reperfusion with or without administration of QSYQ (0.6, 1.2, or 1.8 g/kg) once daily by gavage for 6 days. Post-treatment with QSYQ diminished I/R-induced infarct size, alleviated myocardium injury, attenuated myocardial fibrosis after 6 days of reperfusion, and restored heart function and myocardial blood flow after I/R. In addition, the drug significantly inhibited monocyte infiltration and macrophage polarization towards M2, which was attributable to chemokine RP S19 dimer. Moreover, Western blots revealed that QSYQ blocked I/R-induced increase in TGFβ1 and TGFβRⅡ and reversed its relevant gene expression, such as Smad3,4,6,7, and inhibited the increase of MMP 2,9 expression. As the major components of QSYQ, astragaloside IV (AsIV), 3,4-dihydroxy-phenyl lactic acid (DLA), and notoginsenoside R1 (R1) were assessed as to the contribution of each of them to the expression of the proteins concerned. The results showed that the effect of AsIV was similar to QSYQ, while DLA and R1 only partly simulated the effect of QSYQ. The results provide evidence for the potential role of QSYQ in treating myocardial fibrosis following I/R injury. This effect may be associated with QSYQ's inhibition effect on monocyte chemotaxis and TGFβ1/Smads signaling pathway with different component targeting distinct link (s) of the signaling.

• Authors: Qian-Ning Zheng, Xiao-Hong Wei, Chun-Shui Pan, Quan Li, Yu-Ying Liu, Jing-Yu Fan, Jing-Yan Han
• Journal: Pharmacological research (Pharmacol Res) Vol. 146 Pg. 104272 (08 2019) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 31085230 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Cardiotonic Agents
• Drugs, Chinese Herbal
• RNA, Small Interfering
• Ribosomal Proteins
• Smad Proteins
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• qishen yiqi
• ribosomal protein S19

Topics

• Animals
• Cardiotonic Agents (pharmacology, therapeutic use)
• Cell Line
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Fibrosis
• Macrophages (drug effects)
• Male
• Myocardial Reperfusion Injury (drug therapy, metabolism, pathology)
• Myocardium (metabolism, pathology)
• RNA, Small Interfering (genetics)
• Rats, Sprague-Dawley
• Ribosomal Proteins (genetics, metabolism)
• Signal Transduction (drug effects)
• Smad Proteins (metabolism)
• Transforming Growth Factor beta1 (metabolism)