An integrated pathway interaction network for the combination of four effective compounds from ShengMai preparations in the treatment of cardio-cerebral ischemic diseases

Li, Fang; Lv, Yanni; Tan, Yisha; Shen, Kai; Zhai, Kefeng; Chen, Hong‐Lin; Kou, Junping; Yu, Boyang

doi:10.1038/aps.2015.70

Cited by 22 publications

(13 citation statements)

References 45 publications

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“…As reported in our previous studies ( Tan et al, 2014 ; Li F. et al, 2015 ), the protein database was composed of two parts. Figure 1A depicts the process of this study.…”

Section: Methodsmentioning

confidence: 99%

“…The second part consisted the novel proteins related to the compounds with high affinity, which obtained from the PharmMapper database 3 ( Liu et al, 2010 ). Structures of the three components were established by Sybyl 6.9, and then were employed to all hydrogens and Gastiger-Huckel charges in Sybyl 6.9 in the Tripos force field in an implicit solvent condition ( Li F. et al, 2015 ). The minimization steps included 1000 cycles of steepest descent until meeting convergent threshold of 0.05 kal-1Å-1 ( Tan et al, 2014 ).…”

Section: Methodsmentioning

confidence: 99%

“…The most fundamental feature of the node was its degree, which showed how many links the node with other nodes. The betweenness and the degree were the node topological and centric indexes ( Huang et al, 2009a ; Li F. et al, 2015 ). Higher degree and larger betweenness nodes are most significant ( Barabasi and Oltvai, 2004 ; Opsahl et al, 2010 ).…”

Section: Methodsmentioning

confidence: 99%

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The Combination of Three Components Derived from Sheng MaiSan Protects Myocardial Ischemic Diseases and Inhibits Oxidative Stress via Modulating MAPKs and JAK2-STAT3 Signaling Pathways Based on Bioinformatics Approach

Zeng

Xia

et al. 2017

Front. Pharmacol.

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GRS is a drug combination of three components including ginsenoside Rb1, ruscogenin and schisandrin. It derived from the well-known TCM formula Sheng MaiSan, a widely used traditional Chinese medicine for the treatment of cardiovascular diseases in clinic. The present study illuminates its underlying mechanisms against myocardial ischemic diseases based on the combined methods of bioinformatic prediction and experimental verification. A protein database was established through constructing the drug-protein network. And the target-pathway interaction network clustered the potential signaling pathways and targets of GRS in treatment of myocardial ischemic diseases. Several target proteins, such as NFKB1, STAT3 and MAPK14, were identified as the candidate key proteins, and MAPKs and JAK-STAT signaling pathway were suggested as the most related pathways, which were in accordance with the gene ontology analysis. Then, the predictive results were further validated and we found that GRS treatment alleviated hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury via suppression of MDA levels and ROS generation, and potential mechanisms might related to the suppression of activation of MAPKs and JAK2-STAT3 signaling pathways. Conclusively, our results offer the evidence that GRS attenuates myocardial ischemia injury via regulating oxidative stress and MAPKs and JAK2-STAT3 signaling pathways, which supplied some new insights for its prevention and treatment of myocardial ischemia diseases.

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“…As reported in our previous studies ( Tan et al, 2014 ; Li F. et al, 2015 ), the protein database was composed of two parts. Figure 1A depicts the process of this study.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The Combination of Three Components Derived from Sheng MaiSan Protects Myocardial Ischemic Diseases and Inhibits Oxidative Stress via Modulating MAPKs and JAK2-STAT3 Signaling Pathways Based on Bioinformatics Approach

Zeng

Xia

et al. 2017

Front. Pharmacol.

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“…Network pharmacology has been proven to be a dominant paradigm to decipher the complex pharmacological mechanism of action of effective substances of various herbs, herbal pairs, as well as TCM formulae, by incorporating bioinformatics, cheminformatics, and network biology 68 – 71 . The mystery of herbal pairs and TCM formulae for CVDs is beginning to be revealed with increasing number of studies using network-based approaches, such as compound Danshen formula 72 , compound Saffron formula 73 , Radix Curcumae formula 74 , Shexiang Baoxin pill 75 , QiShenYiQi dropping pill 76 , Huanglian-Jie-Du decoction 77 , ShengMai preparations 78 , Wenxin Keli 79 , Danggui-Honghua pairs 80 and Danshen-Chuanxiong-Honghua pairs 81 . In addition, an integrated network pharmacology approach is employed to unveil the common and distinct molecular mechanism on several highly correlated diseases, such as CVD-gastrointestinal disorders 82 , psoriasis-rheumatoid arthritis 83 , rheumatoid arthritis-CAD 84 and stroke-CAD 16 , 85 , as well as certain TCM subjective theories like Qi-Blood syndrome 86 , Cold-Hot syndrome 87 – 89 .…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology exploration reveals endothelial inflammation as a common mechanism for stroke and coronary artery disease treatment of Danhong injection

Lyu

Yan

Liu

et al. 2017

Sci Rep

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Although Danhong injection (DHI) is the most widely prescribed Chinese medicine for both stroke and coronary artery disease (CAD), its underlying common molecular mechanisms remain unclear. An integrated network pharmacology and experimental verification approach was used to decipher common pharmacological mechanisms of DHI on stroke and CAD treatment. A compound-target-disease & function-pathway network was constructed and analyzed, indicating that 37 ingredients derived from DH (Salvia miltiorrhiza Bge., Flos Carthami tinctorii and DHI) modulated 68 common targets shared by stroke and CAD. In-depth network analysis results of the top diseases, functions, pathways and upstream regulators implied that a common underlying mechanism linking DHI’s role in stroke and CAD treatment was inflammatory response in the process of atherosclerosis. Experimentally, DHI exerted comprehensive anti-inflammatory effects on LPS, ox-LDL or cholesterol crystal-induced NF-κB, c-jun and p38 activation, as well as IL-1β, TNF-α, and IL-10 secretion in vascular endothelial cells. Ten of 14 predicted ingredients were verified to have significant anti-inflammatory activities on LPS-induced endothelial inflammation. DHI exerts pharmacological efficacies on both stroke and CAD through multi-ingredient, multi-target, multi-function and multi-pathway mode. Anti-endothelial inflammation therapy serves as a common underlying mechanism. This study provides a new understanding of DHI in clinical application on cardiovascular and cerebrovascular diseases.

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“…To investigate the targets and potential pathways of active components derived from SMS (ginsenoside Rg1, ginsenoside Rb1, schisandrin, etc. ), Li et al used a target-pathway interaction network approach and found that the three main signaling pathways were the nuclear factor (NF)-κB, oxidative stress, and cytokine network pathways [23]. PGC-1α is a central regulator of mitochondrial biogenesis and metabolic regulation [24,25].…”

Section: Discussionmentioning

confidence: 99%

Shengmai San Alleviates Diabetic Cardiomyopathy Through Improvement of Mitochondrial Lipid Metabolic Disorder

Tian¹,

Tang²,

Xu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Shengmai San (SMS), prepared from Panax ginseng, Ophiopogon japonicus, and Schisandra chinensisin, has been widely used to treat ischemic disease. In this study, we investigated whether SMS may exert a beneficial effect in diabetic cardiomyopathy through improvement of mitochondrial lipid metabolism. Methods: A leptin receptor-deficient db/db mouse model was utilized, and lean age-matched C57BLKS mice served as non-diabetic controls. Glucose and lipid profiles, myocardial structure, dimension, and function, and heart weight to tibial length ratio were determined. Myocardial ultrastructural morphology was observed with transmission electron microscopy. Protein expression and activity of oxidative phosphorylation (OXPHOS) complex were assessed using western blotting and microplate assay kits. We also observed cellular viability, mitochondrial membrane potential, OXPHOS complex activity, and cellular ATP level in palmitic acid-stimulated H9C2 cardiomyocytes. Changes in the sirtuin (SIRT1)/AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) pathway and mitochondrial uncoupling signaling were assessed using western blotting and quantitative real-time PCR. Results: Leptin receptor-deficient db/db mice exhibit obesity, hyperglycemia, and hyperlipidemia, accompanied by distinct myocardial hypertrophy and diastolic dysfunction. SMS at a dose of 3 g/kg body weight contributed to a recovery of diabetes-induced myocardial hypertrophy and diastolic dysfunction. SMS administration led to an effective restoration of mitochondrial structure and function both in vivo and in vitro. Furthermore, SMS markedly enhanced SIRT1 and p-AMPKα protein levels and decreased the expression of acetylated-PGC-1α and uncoupling protein 2 protein. SMS also restored the depletion of NRF1 and TFAM levels in diabetic hearts and H9C2 cardiomyocytes. Conclusion: The results indicate that SMS may alleviate diabetes-induced myocardial hypertrophy and diastolic dysfunction by improving mitochondrial lipid metabolism.

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An integrated pathway interaction network for the combination of four effective compounds from ShengMai preparations in the treatment of cardio-cerebral ischemic diseases

Abstract: NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases.

Cited by 22 publications

References 45 publications

The Combination of Three Components Derived from Sheng MaiSan Protects Myocardial Ischemic Diseases and Inhibits Oxidative Stress via Modulating MAPKs and JAK2-STAT3 Signaling Pathways Based on Bioinformatics Approach

The Combination of Three Components Derived from Sheng MaiSan Protects Myocardial Ischemic Diseases and Inhibits Oxidative Stress via Modulating MAPKs and JAK2-STAT3 Signaling Pathways Based on Bioinformatics Approach

Network pharmacology exploration reveals endothelial inflammation as a common mechanism for stroke and coronary artery disease treatment of Danhong injection

Shengmai San Alleviates Diabetic Cardiomyopathy Through Improvement of Mitochondrial Lipid Metabolic Disorder

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