Jie Liao1, Cui Hao1, Wenhua Huang2, Xin Shao1, Yangang Song2, Liangfeng Liu2, Ni Ai1, Xiaohui Fan3. 1. Department of TCM Science and Engineering, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China. 2. Limin Pharmaceutical Factory, Livzon Pharmaceutical Group Inc., Shaoguan 512028, Guangdong, China. 3. Department of TCM Science and Engineering, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China. Electronic address: fanxh@zju.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Shenqi Fuzheng (SQ) is a renowned traditional Chinese medicine extracted from Radix Codonopsis and Radix Astragali. Although SQ is widely used to treat myocardial ischemia-reperfusion (I/R) injury, the molecular mechanisms supporting its clinical application remain elusive. AIM OF THE STUDY: The purpose of current study was to understand its cardioprotective effects at the molecular level using network pharmacology approach. MATERIALS AND METHOD: In an I/R injury animal model, the beneficial pharmacological activities of SQ were confirmed by decreased infarct range observed on drug treated rats versus control group. Additionally, several serum biochemical indicators were in concord with this observation. Subsequently, a microarray experiment was performed to reveal the influence on injured heart at the gene expression level by this TCM injection. We then proposed a network analysis algorithm NTRA to discover the key nodes based on both disease network structure and transcriptomics. Using NRIODN, a method developed by our group previously, the holistic changes on the gene network induced by for I/R injury and SQ treatment were evaluated. RESULTS: Pathway enrichment analysis of highly ranked genes by NTRA showed that PPAR and apoptosis pathways were highly related to I/R injury. Finally, western blot results showed increased level of the PPARα and BAX protein in the heart after injection treatment which confirmed the hypothesis. CONCLUSION: In conclusion, our results suggest that SQ injection exerts protective effect against myocardial ischemia-reperfusion injury through multiple pathways, including myocardial energy metabolism improvement, cell adhesion inhibition, inflammatory reaction perturbation, myocardial apoptosis reduction and ventricular remodeling avoidance.
ETHNOPHARMACOLOGICAL RELEVANCE: Shenqi Fuzheng (SQ) is a renowned traditional Chinese medicine extracted from Radix Codonopsis and Radix Astragali. Although SQ is widely used to treat myocardial ischemia-reperfusion (I/R) injury, the molecular mechanisms supporting its clinical application remain elusive. AIM OF THE STUDY: The purpose of current study was to understand its cardioprotective effects at the molecular level using network pharmacology approach. MATERIALS AND METHOD: In an I/R injury animal model, the beneficial pharmacological activities of SQ were confirmed by decreased infarct range observed on drug treated rats versus control group. Additionally, several serum biochemical indicators were in concord with this observation. Subsequently, a microarray experiment was performed to reveal the influence on injured heart at the gene expression level by this TCM injection. We then proposed a network analysis algorithm NTRA to discover the key nodes based on both disease network structure and transcriptomics. Using NRIODN, a method developed by our group previously, the holistic changes on the gene network induced by for I/R injury and SQ treatment were evaluated. RESULTS: Pathway enrichment analysis of highly ranked genes by NTRA showed that PPAR and apoptosis pathways were highly related to I/R injury. Finally, western blot results showed increased level of the PPARα and BAX protein in the heart after injection treatment which confirmed the hypothesis. CONCLUSION: In conclusion, our results suggest that SQ injection exerts protective effect against myocardial ischemia-reperfusion injury through multiple pathways, including myocardial energy metabolism improvement, cell adhesion inhibition, inflammatory reaction perturbation, myocardial apoptosis reduction and ventricular remodeling avoidance.