Prediction of Molecular Mechanisms for LianXia NingXin Formula: A Network Pharmacology Study
Objectives: Network pharmacological methods were used to investigate the underlying molecular mechanisms of LianXia NingXin (LXNX) formula, a Chinese prescription, to treat coronary heart disease (CHD) and disease phenotypes (CHD related diseases and symptoms).Methods: The different seed gene lists...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-05-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2018.00489/full |
| _version_ | 1819298677636726784 |
|---|---|
| author | Yang Yang Kuo Yang Teng Hao Guodong Zhu Ruby Ling Xuezhong Zhou Ping Li |
| author_facet | Yang Yang Kuo Yang Teng Hao Guodong Zhu Ruby Ling Xuezhong Zhou Ping Li |
| author_sort | Yang Yang |
| collection | DOAJ |
| description | Objectives: Network pharmacological methods were used to investigate the underlying molecular mechanisms of LianXia NingXin (LXNX) formula, a Chinese prescription, to treat coronary heart disease (CHD) and disease phenotypes (CHD related diseases and symptoms).Methods: The different seed gene lists associated with the herbs of LXNX formula, the CHD co-morbid diseases and symptoms which were relieved by the LXNX formula (co-morbid diseases and symptoms) were curated manually from biomedical databases and published biomedical literatures. Module enrichment analysis was used to identify CHD-related disease modules in the protein–protein interaction (PPI) network which were also associated to the targets of LXNX formula (LXNX formula’s CHD modules). The molecular characteristics of LXNX formula’s CHD modules were investigated via functional enrichment analysis in terms of gene ontology and pathways. We performed shortest path analysis to explore the interactions between the drug targets of LXNX formula and CHD related disease phenotypes (e.g., co-morbid diseases and symptoms).Results: We identified two significant CHD related disease modules (i.e., M146 and M203), which were targeted by the herbs of LXNX formula. Pathway and GO term functional analysis results indicated that G-protein coupled receptor signaling pathways (GPCR) of M146 and cellular protein metabolic process of M203 are important functional pathways for the respective module. This is further confirmed by the shortest path analysis between the drug targets of LXNX formula and the aforementioned disease modules. In addition, corticotropin releasing hormone (CRH) and natriuretic peptide precursor A (NPPA) are the only two LXNX formula target proteins with the low shortest path length (on average shorter than 3) to their respective CHD module and co-morbid disease and symptom gene groups.Conclusion: G-protein coupled receptor signaling pathway and cellular protein metabolic process are the key LXNX formula’s pathways to treat CHD disease phenotypes, in which CRH and NPPA are the two key drug targets of LXNX formula. Further evidences from Chinese herb pharmacological databases indicate that Pinellia ternata (Banxia) has relatively strong adjustive functions on the two key targets. |
| first_indexed | 2024-12-24T05:33:42Z |
| format | Article |
| id | doaj.art-c8e74aa7df7c44d89d258ef89a4be7f3 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-24T05:33:42Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-c8e74aa7df7c44d89d258ef89a4be7f32022-12-21T17:13:06ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-05-01910.3389/fphys.2018.00489346755Prediction of Molecular Mechanisms for LianXia NingXin Formula: A Network Pharmacology StudyYang Yang0Kuo Yang1Teng Hao2Guodong Zhu3Ruby Ling4Xuezhong Zhou5Ping Li6The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, ChinaBeijing Key Lab of Traffic Data Analysis and Mining, School of Computer and Information Technology, Beijing Jiaotong University, Beijing, ChinaDepartment of Psychiatry, Beijing ChaoYang Hospital of Traditional Chinese Medicine, Beijing, ChinaDepartment of Cardiovascular, Beijing Chaoyang Integrative Medicine Emergency Medical Center, Beijing, ChinaThe Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, ChinaBeijing Key Lab of Traffic Data Analysis and Mining, School of Computer and Information Technology, Beijing Jiaotong University, Beijing, ChinaThe Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, ChinaObjectives: Network pharmacological methods were used to investigate the underlying molecular mechanisms of LianXia NingXin (LXNX) formula, a Chinese prescription, to treat coronary heart disease (CHD) and disease phenotypes (CHD related diseases and symptoms).Methods: The different seed gene lists associated with the herbs of LXNX formula, the CHD co-morbid diseases and symptoms which were relieved by the LXNX formula (co-morbid diseases and symptoms) were curated manually from biomedical databases and published biomedical literatures. Module enrichment analysis was used to identify CHD-related disease modules in the protein–protein interaction (PPI) network which were also associated to the targets of LXNX formula (LXNX formula’s CHD modules). The molecular characteristics of LXNX formula’s CHD modules were investigated via functional enrichment analysis in terms of gene ontology and pathways. We performed shortest path analysis to explore the interactions between the drug targets of LXNX formula and CHD related disease phenotypes (e.g., co-morbid diseases and symptoms).Results: We identified two significant CHD related disease modules (i.e., M146 and M203), which were targeted by the herbs of LXNX formula. Pathway and GO term functional analysis results indicated that G-protein coupled receptor signaling pathways (GPCR) of M146 and cellular protein metabolic process of M203 are important functional pathways for the respective module. This is further confirmed by the shortest path analysis between the drug targets of LXNX formula and the aforementioned disease modules. In addition, corticotropin releasing hormone (CRH) and natriuretic peptide precursor A (NPPA) are the only two LXNX formula target proteins with the low shortest path length (on average shorter than 3) to their respective CHD module and co-morbid disease and symptom gene groups.Conclusion: G-protein coupled receptor signaling pathway and cellular protein metabolic process are the key LXNX formula’s pathways to treat CHD disease phenotypes, in which CRH and NPPA are the two key drug targets of LXNX formula. Further evidences from Chinese herb pharmacological databases indicate that Pinellia ternata (Banxia) has relatively strong adjustive functions on the two key targets.http://journal.frontiersin.org/article/10.3389/fphys.2018.00489/fullNPPACRHnetwork pharmacologycoronary heart diseaseLianXia NingXin formulapharmacological target |
| spellingShingle | Yang Yang Kuo Yang Teng Hao Guodong Zhu Ruby Ling Xuezhong Zhou Ping Li Prediction of Molecular Mechanisms for LianXia NingXin Formula: A Network Pharmacology Study Frontiers in Physiology NPPA CRH network pharmacology coronary heart disease LianXia NingXin formula pharmacological target |
| title | Prediction of Molecular Mechanisms for LianXia NingXin Formula: A Network Pharmacology Study |
| title_full | Prediction of Molecular Mechanisms for LianXia NingXin Formula: A Network Pharmacology Study |
| title_fullStr | Prediction of Molecular Mechanisms for LianXia NingXin Formula: A Network Pharmacology Study |
| title_full_unstemmed | Prediction of Molecular Mechanisms for LianXia NingXin Formula: A Network Pharmacology Study |
| title_short | Prediction of Molecular Mechanisms for LianXia NingXin Formula: A Network Pharmacology Study |
| title_sort | prediction of molecular mechanisms for lianxia ningxin formula a network pharmacology study |
| topic | NPPA CRH network pharmacology coronary heart disease LianXia NingXin formula pharmacological target |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2018.00489/full |
| work_keys_str_mv | AT yangyang predictionofmolecularmechanismsforlianxianingxinformulaanetworkpharmacologystudy AT kuoyang predictionofmolecularmechanismsforlianxianingxinformulaanetworkpharmacologystudy AT tenghao predictionofmolecularmechanismsforlianxianingxinformulaanetworkpharmacologystudy AT guodongzhu predictionofmolecularmechanismsforlianxianingxinformulaanetworkpharmacologystudy AT rubyling predictionofmolecularmechanismsforlianxianingxinformulaanetworkpharmacologystudy AT xuezhongzhou predictionofmolecularmechanismsforlianxianingxinformulaanetworkpharmacologystudy AT pingli predictionofmolecularmechanismsforlianxianingxinformulaanetworkpharmacologystudy |