Screening of the key response component groups and mechanism verification of Huangqi-Guizhi-Wuwu-Decoction in treating rheumatoid arthritis based on a novel computational pharmacological model
Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the destruction of synovial tissue and articular cartilage. Huangqi-Guizhi-Wuwu-Decoction (HGWD), a formula of Traditional Chinese Medicine (TCM), has shown promising clinical efficacy in the treatment of...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Complementary Medicine and Therapies |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12906-023-04315-y |
| _version_ | 1797363631948562432 |
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| author | Qinwen Liu Qian Luo Qiling Fan Yi Li Aiping Lu Daogang Guan |
| author_facet | Qinwen Liu Qian Luo Qiling Fan Yi Li Aiping Lu Daogang Guan |
| author_sort | Qinwen Liu |
| collection | DOAJ |
| description | Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the destruction of synovial tissue and articular cartilage. Huangqi-Guizhi-Wuwu-Decoction (HGWD), a formula of Traditional Chinese Medicine (TCM), has shown promising clinical efficacy in the treatment of RA. However, the synergistic effects of key response components group (KRCG) in the treatment of RA have not been well studied. Methods The components and potential targets of HGWD were extracted from published databases. A novel node influence calculation model that considers both the node control force and node bridging force was designed to construct the core response space (CRS) and obtain key effector proteins. An increasing coverage coefficient (ICC) model was employed to select the KRCG. The effectiveness and potential mechanism of action of KRCG were confirmed using CCK-8, qPCR, and western blotting. Results A total of 796 key effector proteins were identified in CRS. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses confirmed their effectiveness and reliability. In addition, 59 components were defined as KRCG, which contributed to 85.05% of the target coverage of effective proteins. Of these, 677 targets were considered key reaction proteins, and their enriched KEGG pathways accounted for 84.89% of the pathogenic genes and 87.94% of the target genes. Finally, four components (moupinamide, 6-Paradol, hydrocinnamic acid, and protocatechuic acid) were shown to inhibit the inflammatory response in RA by synergistically targeting the cAMP, PI3K-Akt, and HIF-1α pathways. Conclusions We have introduced a novel model that aims to optimize and analyze the mechanisms behind herbal formulas. The model revealed the KRCG of HGWD for the treatment of RA and proposed that KRCG inhibits the inflammatory response by synergistically targeting cAMP, PI3K-Akt, and HIF-1α pathways. Overall, the novel model is plausible and reliable, offering a valuable reference for the secondary development of herbal formulas. |
| first_indexed | 2024-03-08T16:23:57Z |
| format | Article |
| id | doaj.art-089cd597da88430dba952fd1ec348360 |
| institution | Directory Open Access Journal |
| issn | 2662-7671 |
| language | English |
| last_indexed | 2024-03-08T16:23:57Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Complementary Medicine and Therapies |
| spelling | doaj.art-089cd597da88430dba952fd1ec3483602024-01-07T12:11:01ZengBMCBMC Complementary Medicine and Therapies2662-76712024-01-0124111510.1186/s12906-023-04315-yScreening of the key response component groups and mechanism verification of Huangqi-Guizhi-Wuwu-Decoction in treating rheumatoid arthritis based on a novel computational pharmacological modelQinwen Liu0Qian Luo1Qiling Fan2Yi Li3Aiping Lu4Daogang Guan5Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical UniversityInstitute of Integrated Bioinformedicine and Translational Science, Hong Kong Baptist UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical UniversityAbstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the destruction of synovial tissue and articular cartilage. Huangqi-Guizhi-Wuwu-Decoction (HGWD), a formula of Traditional Chinese Medicine (TCM), has shown promising clinical efficacy in the treatment of RA. However, the synergistic effects of key response components group (KRCG) in the treatment of RA have not been well studied. Methods The components and potential targets of HGWD were extracted from published databases. A novel node influence calculation model that considers both the node control force and node bridging force was designed to construct the core response space (CRS) and obtain key effector proteins. An increasing coverage coefficient (ICC) model was employed to select the KRCG. The effectiveness and potential mechanism of action of KRCG were confirmed using CCK-8, qPCR, and western blotting. Results A total of 796 key effector proteins were identified in CRS. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses confirmed their effectiveness and reliability. In addition, 59 components were defined as KRCG, which contributed to 85.05% of the target coverage of effective proteins. Of these, 677 targets were considered key reaction proteins, and their enriched KEGG pathways accounted for 84.89% of the pathogenic genes and 87.94% of the target genes. Finally, four components (moupinamide, 6-Paradol, hydrocinnamic acid, and protocatechuic acid) were shown to inhibit the inflammatory response in RA by synergistically targeting the cAMP, PI3K-Akt, and HIF-1α pathways. Conclusions We have introduced a novel model that aims to optimize and analyze the mechanisms behind herbal formulas. The model revealed the KRCG of HGWD for the treatment of RA and proposed that KRCG inhibits the inflammatory response by synergistically targeting cAMP, PI3K-Akt, and HIF-1α pathways. Overall, the novel model is plausible and reliable, offering a valuable reference for the secondary development of herbal formulas.https://doi.org/10.1186/s12906-023-04315-yRheumatoid arthritisHuangqi-Guizhi-Wuwu-DecoctionNetwork pharmacologyKey response components group |
| spellingShingle | Qinwen Liu Qian Luo Qiling Fan Yi Li Aiping Lu Daogang Guan Screening of the key response component groups and mechanism verification of Huangqi-Guizhi-Wuwu-Decoction in treating rheumatoid arthritis based on a novel computational pharmacological model BMC Complementary Medicine and Therapies Rheumatoid arthritis Huangqi-Guizhi-Wuwu-Decoction Network pharmacology Key response components group |
| title | Screening of the key response component groups and mechanism verification of Huangqi-Guizhi-Wuwu-Decoction in treating rheumatoid arthritis based on a novel computational pharmacological model |
| title_full | Screening of the key response component groups and mechanism verification of Huangqi-Guizhi-Wuwu-Decoction in treating rheumatoid arthritis based on a novel computational pharmacological model |
| title_fullStr | Screening of the key response component groups and mechanism verification of Huangqi-Guizhi-Wuwu-Decoction in treating rheumatoid arthritis based on a novel computational pharmacological model |
| title_full_unstemmed | Screening of the key response component groups and mechanism verification of Huangqi-Guizhi-Wuwu-Decoction in treating rheumatoid arthritis based on a novel computational pharmacological model |
| title_short | Screening of the key response component groups and mechanism verification of Huangqi-Guizhi-Wuwu-Decoction in treating rheumatoid arthritis based on a novel computational pharmacological model |
| title_sort | screening of the key response component groups and mechanism verification of huangqi guizhi wuwu decoction in treating rheumatoid arthritis based on a novel computational pharmacological model |
| topic | Rheumatoid arthritis Huangqi-Guizhi-Wuwu-Decoction Network pharmacology Key response components group |
| url | https://doi.org/10.1186/s12906-023-04315-y |
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