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Fuling-Guizhi Herb Pair in Coronary Heart Disease: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation.

ABSTRACT: The Fuling (Poria cocos)-Guizhi (Cinnamomi ramulus) herb pair (FGHP) is a commonly used traditional Chinese herbal formula with coronary heart disease (CHD) treatment potential. However, the mechanism of FGHP in the treatment of CHD was still unclear. In this study, the action targets and underlying mechanism of FGHP against CHD were successfully achieved by combined network pharmacology prediction with experimental verification. 76 common targets were screened out by overlapping the chemical-protein data of FGHP and CHD-related targets. Then, two key targets were further selected for verification by using western blot analysis after analyzing PPI, GO function, and KEGG pathway. Results indicated FGHP could alleviate CHD syndromes and regulate inflammatory responses in acute myocardial ischemia rats, and the reduction of expression of TNF-? and IL-6 in myocardial tissue would be one of its possible underlying mechanisms. Our work demonstrated that network pharmacology combined with experimental verification provides a credible method to elucidate the pharmacological mechanism of FGHP against CHD.

SUBMITTER: Duan B

PROVIDER: S-EPMC7251461 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Fuling-Guizhi Herb Pair in Coronary Heart Disease: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation.

Duan Bailu B Han Lintao L Ming Shuping S Li JingJing J Wang Qiong Q Zhang Dongning D Tian Guangyu G Huang Fang F

Evidence-based complementary and alternative medicine : eCAM 20200517

The Fuling (<i>Poria cocos</i>)-Guizhi (<i>Cinnamomi ramulus</i>) herb pair (FGHP) is a commonly used traditional Chinese herbal formula with coronary heart disease (CHD) treatment potential. However, the mechanism of FGHP in the treatment of CHD was still unclear. In this study, the action targets and underlying mechanism of FGHP against CHD were successfully achieved by combined network pharmacology prediction with experimental verification. 76 common targets were screened out by overlapping t ...[more]

PMID: 32508942

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Project description:AimThis study aimed to predict the key targets and endocrine mechanisms of Guizhi Fuling Wan (GZFLW) in treating adenomyosis (AM) through network pharmacology, molecular docking, and animal experiment verification.MethodsThe related ingredients and targets of GZFLW in treating AM were screened out using TCMSP, BATMAN-TCM, SwissTargetPrediction, and PubChem Database. Then, the protein-protein interaction (PPI) analysis and the network of compound-hub targets were constructed. At the same time, the key targets were uploaded to the Metascape Database for KEGG pathway enrichment analysis. After that, the molecular docking technology of the main active components and hub targets was performed. Furthermore, animal experiments were used to verify the results of network pharmacology analysis.ResultsA total of 55 active ingredients of GZFLW and 44 overlapping targets of GZFLW in treating AM were obtained. After screening, 25 hub targets were collected, including ESR1, EGF, and EGFR. Then, the KEGG pathway enrichment analysis results indicated that the endocrine therapeutic mechanism of GZFLW against AM is mainly associated with the estrogen signaling pathway, endocrine resistance, and an EGFR tyrosine kinase signaling pathway. Then, molecular docking showed that the significant compounds of GZFLW had a strong binding ability with ERα and EGFR. More importantly, the animal experiments confirmed that the GZFLW could downregulate the abnormal infiltration of the endometrial epithelium into the myometrium and had no interference with the normal sexual cycle. This effect may be directly related to intervening the local estrogen signaling pathway of the endometrial myometrial interface (EMI). It may also be associated with the myometrium cells' estrogen resistance via GPER/EGFR signaling pathway.ConclusionThe endocrine mechanism of GZFLW in treating AM was explored based on network pharmacology, molecular docking, and animal experiments, which provided a theoretical basis for the clinical application of GZFLW.

Project description:BackgroundCoronary heart disease (CHD) seriously affects human health, and its pathogenesis is closely related to atherosclerosis. The Huzhang (the root of Polygonum cuspidatum)-Shanzha (the fruit of Crataegus sp.), a classic herb pair, has been widely used for the treatment of CHD. In recent years, Huzhang-Shanzha herb pair (HSHP) was found to have a wide range of effects in CHD; however, its therapeutic specific mechanisms remain to be further explored. The aim of this study was to elucidate the molecular mechanism of HSHP in the treatment of CHD using a network pharmacology analysis approach.MethodsThe Batman-TCM database was used to explore bioactive compounds and corresponding targets of HSHP. CHD disease targets were extracted from Genecards, OMIM, PharmGkb, TTD, and DrugBank databases. Then, the protein-protein interaction (PPI) network was constructed using the STRING web platform and Cytoscape software. GO functional and KEGG pathway enrichment analyses were carried out on the Metascape web platform. Finally, molecular docking of the active components was assessed to verify the potential targets of HSHP to treat CHD by the AutoDock Vina and PyMOL software.ResultsTotally, 243 active components and 2459 corresponding targets of LDP were screened out. Eighty-five common targets of HSHP and CHD were identified. The results of the network analysis showed that resveratrol, anthranone, emodin, and ursolic acid could be defined as four therapeutic components. TNF, ESR1, NFКB1, PPARG, INS, TP53, NFКBIA, AR, PIK3R1, PIK3CA, PTGS2, and NR3C1 might be the 12 key targets. These targets were mainly involved in the regulation of biological processes, such as inflammatory responses and lipid metabolism. Enrichment analysis showed that the identified genes were mainly involved in fluid shear force, insulin resistance (IR), inflammation, and lipid metabolism pathways to contribute to CHD. This suggests that resveratrol, anthranone, emodin, and ursolic acid from HSHP can be the main therapeutic components of atherosclerosis.ConclusionUsing network pharmacology, we provide new clues on the potential mechanism of action of HSHP in the treatment of CHD, which may be closely related to the fluid shear force, lipid metabolism, and inflammatory response.

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Project description:BackgroundGuizhi Fuling Wan (GZFLW) is a widely used classical Chinese herbal formulae prescribed for the treatment of endometriosis (EMs). This study aimed to predict the key targets and mechanisms of GZFLW in the treatment of EMs by network pharmacology and molecular docking.MethodsFirstly, related compounds and targets of GZFLW were identified through the TCMSP, BATMAN-TCM and CASC database. Then, the EMs target database was built by GeneCards. The overlapping targets between GZFLW and EMs were screened out, and then data of the PPI network was obtained by the STRING Database to analyze the interrelationship of these targets. Furthermore, a topological analysis was performed to screen the hub targets. After that, molecular docking technology was used to confirm the binding degree of the main active compounds and hub targets. Finally, the DAVID database and Metascape database were used for GO and KEGG enrichment analysis.ResultsA total of 89 GZFLW compounds and 284 targets were collected. One hundred one matching targets were picked out as the correlative targets of GZFLW in treating EMs. Among these, 25 significant hub targets were recognized by the PPI network. Coincidently, molecular docking simulation indicated that the hub targets had a good bonding activity with most active compounds (69.71%). Furthermore, 116 items, including the inflammatory reaction, RNA polymerase, DNA transcription, growth factor activity, and steroid-binding, were selected by GO enrichment analysis. Moreover, the KEGG enrichment analysis results included 100 pathways focused on the AGE-RAGE pathway, HIF pathway, PI3K Akt pathway, MAPK pathway, and TP53 pathway, which exposed the potential mechanisms of GZFLW in treating EMs. Also, the MTT colorimetric assay indicated that the cell proliferation could be inhibited by GZFLW. Compared with the control group, the protein levels of P53, BAX, and caspase3 in the drug groups were all increased in Western blotting results. The results of flow cytometry showed that the percentage of apoptotic cells in the GZFLW group was significantly higher than that in the control group.ConclusionThrough the exploration of network pharmacology and molecular docking technology, GZFLW has a therapeutic effect on EMs through multi-target mechanism. This study provided a good foundation for further experimental research.

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Dataset Information

Fuling-Guizhi Herb Pair in Coronary Heart Disease: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation.

Publications

Fuling-Guizhi Herb Pair in Coronary Heart Disease: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation.

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