Target Identification of Active Constituents of Shen Qi Wan to Treat Kidney Yang Deficiency Using Computational Target Fishing and Network Pharmacology

Zhang, Jie Ying; Hong, Chunlan; Chen, Hong Shu; Zhang, Xiao; Zhang, Yu Jia; Efferth, Thomas; Yang, Yuan; Li, Chang Yu

doi:10.3389/fphar.2019.00650

Cited by 34 publications

(20 citation statements)

References 70 publications

(45 reference statements)

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“…This flowchart really solves the molecular mechanism of some formulas of TCM in treating complex diseases. Such as: Hua Yu Qiang Shen Tong Bi formula treats rheumatoid arthritis ( Wang et al., 2019 ), Shen Qi Wan treats kidney yang deficiency syndrome ( Zhang et al., 2019 ), and Huo Xiang Zheng Qi formula treats functional dyspepsia ( Zhao et al., 2018 ). However, there still exists some problems, such as false positive and noise in the predicted targets of components.…”

Section: Discussionmentioning

confidence: 99%

A Novel Network Pharmacology Strategy to Decode Mechanism of Lang Chuang Wan in Treating Systemic Lupus Erythematosus

Gao

Wang

et al. 2020

Front. Pharmacol.

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Complex disease is a cascade process which is associated with functional abnormalities in multiple proteins and protein-protein interaction (PPI) networks. One drug one target has not been able to perfectly intervene complex diseases. Increasing evidences show that Chinese herb formula usually treats complex diseases in the form of multi-components and multi-targets. The key step to elucidate the underlying mechanism of formula in traditional Chinese medicine (TCM) is to optimize and capture the important components in the formula. At present, there are several formula optimization models based on network pharmacology has been proposed. Most of these models focus on the 2D/3D similarity of chemical structure of drug components and ignore the functional optimization space based on relationship between pathogenetic genes and drug targets. How to select the key group of effective components (KGEC) from the formula of TCM based on the optimal space which link pathogenic genes and drug targets is a bottleneck problem in network pharmacology. To address this issue, we designed a novel network pharmacological model, which takes Lang Chuang Wan (LCW) treatment of systemic lupus erythematosus (SLE) as the case. We used the weighted gene regulatory network and active components targets network to construct disease-targets-components network, after filtering through the network attribute degree, the optimization space and effective proteins were obtained. And then the KGEC was selected by using contribution index (CI) model based on knapsack algorithm. The results show that the enriched pathways of effective proteins we selected can cover 96% of the pathogenetic genes enriched pathways. After reverse analysis of effective proteins and optimization with CI index model, KGEC with 82 components were obtained, and 105 enriched pathways of KGEC targets were consistent with enriched pathways of pathogenic genes (80.15%). Finally, the key components in KGEC of LCW were evaluated by in vitro experiments. These results indicate that the proposed model with good accuracy in screening the KGEC in the formula of TCM, which provides reference for the optimization and mechanism analysis of the formula in TCM.

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Section: Discussionmentioning

confidence: 99%

A Novel Network Pharmacology Strategy to Decode Mechanism of Lang Chuang Wan in Treating Systemic Lupus Erythematosus

Gao

Wang

et al. 2020

Front. Pharmacol.

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“…Besides, DHG treatment not only inhibited the fat accumulation in the liver, but also inversed the increase of body weight gain, liver index, and related adipose tissue weight in hyperlipidemic hamsters, which further confirmed that the DHG had a beneficial lipidlowering effect. Systems pharmacology has gradually become an effective method to study the active components and mechanisms of action of TCM (Zhou et al, 2019;Zhang et al, 2019). Different from most of the previous studies that usually consider ingredients from herbal databases, we take the compounds that are detected in the hamster blood as the compound source to carry out systems pharmacology research.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the Lipid-Lowering Mechanisms and Active Ingredients of Danhe Granule on Hyperlipidemia Based on Systems Pharmacology

Chen

Yan

et al. 2020

Front. Pharmacol.

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Objective: Investigate the active ingredients and underlying hypolipidemic mechanisms of Danhe granule (DHG). Methods: The lipid-lowering effect of DHG was evaluated in hyperlipidemic hamsters induced by a high-fat diet. The ingredients absorbed into the blood after oral administration of DHG in hamsters were identified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). A systems pharmacology approach incorporating target prediction and network construction, gene ontology (GO) enrichment and pathway analysis was performed to predict the active compounds and map the compounds-targets-disease network. Real-time polymerase chain reaction (RT-PCR) and Western blot were utilized to analyze the mRNA and protein expression levels of predicted targets. Results: DHG remarkably lowered the levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and arteriosclerosis index (AI), at the same time, elevated the levels of serum high-density lipoprotein cholesterol (HDL-c) and HDL-c/TC ratio in hyperlipidemic hamsters. Sixteen ingredients absorbed into blood after oral administration of DHG were identified as the possible components interacted with targets. Moreover, 65 potential targets were predicted after targets intersection and compounds-targets-disease network mapping. Then, compounds-targets-pathways network mapping revealed that six active compounds (emodin, naringenin, etc.) compounds could interact with 10 targets such as sterol regulatory element binding protein (SREBP) 1c, SREBP-2 and peroxisome proliferation-activated receptor (PPAR) a, regulate three lipid metabolism-related pathways including SREBP control of lipid synthesis pathway, PPAR signaling pathway and nuclear receptors in lipid metabolism and toxicity pathway, and further affect lipid metabolic processes including fatty acid biosynthesis, low-density lipoprotein receptor (LDLR)-mediated cholesterol uptake, bile acid biosynthesis, and cholesterol efflux. Experimental results indicated that DHG significantly increased SREBP-2, LDLR, PPARa, liver X receptor alpha (LXRa),

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“…Applications of network pharmacology to investigate mechanism of TCM have become an indispensable method for development of TCM [7]. In many previous studies, network pharmacology has successfully predicted potential targets and pathways of TCM [8][9][10]. erefore, network pharmacology has been proved to be an effective method to explore potential targets and pathways of TCM by analyzing network of biological systems.…”

Section: Introductionmentioning

confidence: 99%

Systematic Elucidation of the Potential Mechanism of Erzhi Pill against Drug‐Induced Liver Injury via Network Pharmacology Approach

Huang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. e purpose of this work was to investigate the bioactive compounds, core genes, and pharmacological mechanisms and to provide a further research orientation of Erzhi pill (EZP) on drug-induced liver injury (DILI). Methods. At first, we collected information of bioactive compounds of EZP from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and previous studies. And then, the targets related to bioactive compounds and DILI were obtained from 4 public databases. At last, Cytoscape was used to establish a visual network. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and network analysis were performed to investigate potential mechanism of EZP against DILI. Results. A total of 23 bioactive compounds and 89 major proteins of EZP were screened out as potential players against DILI. Association for bioactive compounds, core targets, and related pathways was analyzed, implying that core targets related to these pathways are ALB, AKT1, MAPK1, EGFR, SRC, MAPK8, IGF1, CASP3, HSP90AA1, and MMP9, and potential mechanisms of EZP acting on DILI are closely related to negative regulation of apoptosis process, improvement of lipid metabolism, and positive regulation of liver regeneration process. Conclusion. is study demonstrated the multicompound, multitarget, and multichannel characteristics of EZP, which provided a novel approach for further research the mechanism of EZP in the treatment of DILI.

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Target Identification of Active Constituents of Shen Qi Wan to Treat Kidney Yang Deficiency Using Computational Target Fishing and Network Pharmacology

Cited by 34 publications

References 70 publications

A Novel Network Pharmacology Strategy to Decode Mechanism of Lang Chuang Wan in Treating Systemic Lupus Erythematosus

A Novel Network Pharmacology Strategy to Decode Mechanism of Lang Chuang Wan in Treating Systemic Lupus Erythematosus

Investigation of the Lipid-Lowering Mechanisms and Active Ingredients of Danhe Granule on Hyperlipidemia Based on Systems Pharmacology

Systematic Elucidation of the Potential Mechanism of Erzhi Pill against Drug‐Induced Liver Injury via Network Pharmacology Approach

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