A network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum Moldavica L. in the treatment of cardiovascular diseases
Abstract Aim of the study Cardiovascular disease (CVD) seriously endangers human health and is characterized by high mortality and disability. The effectiveness of Dracocephalum moldavica L. in the treatment of CVD has been proven by clinical practice. However, the mechanism by which DML can treat C...
| 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/s12906-023-04316-x |
| _version_ | 1797363684201201664 |
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| author | Rui-fang Zheng Kaderyea Kader Di-wei Liu Wen-ling Su Lei Xu Yuan-yuan Jin Jian-guo Xing |
| author_facet | Rui-fang Zheng Kaderyea Kader Di-wei Liu Wen-ling Su Lei Xu Yuan-yuan Jin Jian-guo Xing |
| author_sort | Rui-fang Zheng |
| collection | DOAJ |
| description | Abstract Aim of the study Cardiovascular disease (CVD) seriously endangers human health and is characterized by high mortality and disability. The effectiveness of Dracocephalum moldavica L. in the treatment of CVD has been proven by clinical practice. However, the mechanism by which DML can treat CVD has not been systematically determined. Materials and methods The active compounds in DML were screened by literature mining and pharmacokinetic analysis. Cytoscape software was used to construct the target-disease interaction network of DML in the treatment of CVD. Gene ontology and signalling pathway enrichment analyses were performed. The key target pathway network of DML compounds was constructed and verified by pharmacological experiments in vitro. A hydrogen glucose deprivation/reoxygenation model was established in H9c2 cells using hypoxia and glucose deprivation for 9 h combined with reoxygenation for 2 h. The model simulated myocardial ischaemic reperfusion injury to investigate the effects of total flavonoids of Cymbidium on cell viability, myocardial injury markers, oxidative stress levels, and reactive oxygen radical levels. Western blot analysis was used to examine NOX-4, Bcl-2/Bax, and PGC-1α protein expression. Results Twenty-seven active components were screened, and 59 potential drug targets for the treatment of CVD were obtained. Through the compound-target interaction network and the target-disease interaction network, the key targets and key signalling pathways, such as NOX-4, Bcl-2/Bax and PGC-1α, were obtained. TFDM significantly decreased LDH and MDA levels and the production of ROS and increased SOD activity levels in the context of OGD/R injury. Further studies indicated that NOX-4 and Bax protein levels and the p-P38 MAPK/P38 MAPK andp-Erk1/2/Erk1/2 ratios were suppressed by TFDM. The protein expression of Bcl-2 and PGC-1α was increased by TFDM. Conclusions Our results showed that DML had multicomponent, multitarget and multichannel characteristics in the treatment of CVD. The mechanism may be associated with the following signalling pathways: 1) the NOX-4/ROS/p38 MAPK signalling pathway, which inhibits inflammation and reactive oxygen species (ROS) production, and 2) the Bcl-2/Bax and AMPK/SIRT1/PGC-1α signalling pathways, which inhibit apoptosis. |
| first_indexed | 2024-03-08T16:24:30Z |
| format | Article |
| id | doaj.art-a5519763f5ed4c21871195685d88c14a |
| institution | Directory Open Access Journal |
| issn | 2662-7671 |
| language | English |
| last_indexed | 2024-03-08T16:24:30Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Complementary Medicine and Therapies |
| spelling | doaj.art-a5519763f5ed4c21871195685d88c14a2024-01-07T12:10:58ZengBMCBMC Complementary Medicine and Therapies2662-76712024-01-0124111610.1186/s12906-023-04316-xA network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum Moldavica L. in the treatment of cardiovascular diseasesRui-fang Zheng0Kaderyea Kader1Di-wei Liu2Wen-ling Su3Lei Xu4Yuan-yuan Jin5Jian-guo Xing6Xinjiang Key Laboratory of Uygur Medical Research, Xinjiang Institute of Materia MedicaXinjiang Key Laboratory of Uygur Medical Research, Xinjiang Institute of Materia MedicaXinjiang Key Laboratory of Uygur Medical Research, Xinjiang Institute of Materia MedicaXinjiang Key Laboratory of Uygur Medical Research, Xinjiang Institute of Materia MedicaXinjiang Key Laboratory of Uygur Medical Research, Xinjiang Institute of Materia MedicaInstitute of Medicinal Biotechnology, Dongcheng District, Chinese Academy of Medical SciencesXinjiang Key Laboratory of Uygur Medical Research, Xinjiang Institute of Materia MedicaAbstract Aim of the study Cardiovascular disease (CVD) seriously endangers human health and is characterized by high mortality and disability. The effectiveness of Dracocephalum moldavica L. in the treatment of CVD has been proven by clinical practice. However, the mechanism by which DML can treat CVD has not been systematically determined. Materials and methods The active compounds in DML were screened by literature mining and pharmacokinetic analysis. Cytoscape software was used to construct the target-disease interaction network of DML in the treatment of CVD. Gene ontology and signalling pathway enrichment analyses were performed. The key target pathway network of DML compounds was constructed and verified by pharmacological experiments in vitro. A hydrogen glucose deprivation/reoxygenation model was established in H9c2 cells using hypoxia and glucose deprivation for 9 h combined with reoxygenation for 2 h. The model simulated myocardial ischaemic reperfusion injury to investigate the effects of total flavonoids of Cymbidium on cell viability, myocardial injury markers, oxidative stress levels, and reactive oxygen radical levels. Western blot analysis was used to examine NOX-4, Bcl-2/Bax, and PGC-1α protein expression. Results Twenty-seven active components were screened, and 59 potential drug targets for the treatment of CVD were obtained. Through the compound-target interaction network and the target-disease interaction network, the key targets and key signalling pathways, such as NOX-4, Bcl-2/Bax and PGC-1α, were obtained. TFDM significantly decreased LDH and MDA levels and the production of ROS and increased SOD activity levels in the context of OGD/R injury. Further studies indicated that NOX-4 and Bax protein levels and the p-P38 MAPK/P38 MAPK andp-Erk1/2/Erk1/2 ratios were suppressed by TFDM. The protein expression of Bcl-2 and PGC-1α was increased by TFDM. Conclusions Our results showed that DML had multicomponent, multitarget and multichannel characteristics in the treatment of CVD. The mechanism may be associated with the following signalling pathways: 1) the NOX-4/ROS/p38 MAPK signalling pathway, which inhibits inflammation and reactive oxygen species (ROS) production, and 2) the Bcl-2/Bax and AMPK/SIRT1/PGC-1α signalling pathways, which inhibit apoptosis.https://doi.org/10.1186/s12906-023-04316-xTotal Flavonoids from Dracocephalum Moldavica LCardiovascular diseaseNetwork pharmacologyPharmacological evaluationRecombinant NADPH oxidase 4 |
| spellingShingle | Rui-fang Zheng Kaderyea Kader Di-wei Liu Wen-ling Su Lei Xu Yuan-yuan Jin Jian-guo Xing A network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum Moldavica L. in the treatment of cardiovascular diseases BMC Complementary Medicine and Therapies Total Flavonoids from Dracocephalum Moldavica L Cardiovascular disease Network pharmacology Pharmacological evaluation Recombinant NADPH oxidase 4 |
| title | A network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum Moldavica L. in the treatment of cardiovascular diseases |
| title_full | A network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum Moldavica L. in the treatment of cardiovascular diseases |
| title_fullStr | A network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum Moldavica L. in the treatment of cardiovascular diseases |
| title_full_unstemmed | A network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum Moldavica L. in the treatment of cardiovascular diseases |
| title_short | A network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum Moldavica L. in the treatment of cardiovascular diseases |
| title_sort | network pharmacology approach to decipher the mechanism of total flavonoids from dracocephalum moldavica l in the treatment of cardiovascular diseases |
| topic | Total Flavonoids from Dracocephalum Moldavica L Cardiovascular disease Network pharmacology Pharmacological evaluation Recombinant NADPH oxidase 4 |
| url | https://doi.org/10.1186/s12906-023-04316-x |
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