Uncovering the molecular mechanisms of tonifying kidney and activating blood Decoction against myocardial fibrosis using network Pharmacology and experimental validation
Abstract Chronic heart failure(HF) has become a disease of global concern due to its high morbidity and mortality.This has highlighted the need for cardioprotective agents.The Tonifying Kidney and Activating Blood(KTBA) decoction has been approved for clinical treatment of chronic HF.Tanshinone IIA(...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-01276-9 |
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| author | Rui Xu Yanping Bi Yetao Ju Wenhao Yin Shujun Zhao Yan Zhang Xin Zhao |
| author_facet | Rui Xu Yanping Bi Yetao Ju Wenhao Yin Shujun Zhao Yan Zhang Xin Zhao |
| author_sort | Rui Xu |
| collection | DOAJ |
| description | Abstract Chronic heart failure(HF) has become a disease of global concern due to its high morbidity and mortality.This has highlighted the need for cardioprotective agents.The Tonifying Kidney and Activating Blood(KTBA) decoction has been approved for clinical treatment of chronic HF.Tanshinone IIA(Tan IIA), rooted from Salvia miltiorrhiza of KTBA, has been approved for treating cardiovascular conditions.However, the mechanism is still unclear.This study examined the impact of KTBA on cardiomyocyte fibrosis in a rat model of heart failure post-myocardial infarction, induced by ligation of the left anterior descending coronary artery, followed by exhaustive swimming and starvation. Additionally, the effects of Tan IIA on CCD-841CoN cells were assessed under ischemic conditions in a 37 °C incubator with hypoxic environment (1% O2, 5% CO2, and 94% N2). The investigation employed an integrative approach combining network pharmacology with molecular mechanism analysis.The findings of network pharmacology indicate that KTBA may exert its influence by targeting key proteins such as TNF, AKT1, STAT3, RELA (NF-κB p65), NFκBIA (I-κBα), and MAPK14 (p38α).Results showed that KTBA increased SERCA2a level, lowered collagen I and III, α-SMA, and phospholamban levels, reduced collagen fiber deposition, and delayed mitochondria injury.This cardioprotection effect was perhaps due to suppressing the expressions of p38MAPK, I-κBα, NF-κB, AQP4,AKT, PI3K, TNF-α, and STAT3 and increasing the levels of ZO-1 and Occludin in hippocampus of chronic HF rats, which were partially diminished by SB203580 and PDTC.Additionally, Tan IIA reduced levels of p38MAPK, I-κBα, NF-κB, STAT3, and increased levels of AQP4, Claudin-1, ZO-1, and ZO-2,that were reduced by siRNAs targeting p38MAPK, NF-κB, and AQP4.In conclusion, by modulating the p38MAPK/NF-κB/AQP4 axis, KTBA decoction delays cardiomyocyte fibrosis through alleviating hippocampal blood-brain barrier and Tan IIA improves enterocyte barrier integrity. |
| format | Article |
| id | doaj-art-db58191d68a64c25a6a5e666fc805988 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-db58191d68a64c25a6a5e666fc8059882025-08-20T03:16:31ZengNature PortfolioScientific Reports2045-23222025-05-0115112510.1038/s41598-025-01276-9Uncovering the molecular mechanisms of tonifying kidney and activating blood Decoction against myocardial fibrosis using network Pharmacology and experimental validationRui Xu0Yanping Bi1Yetao Ju2Wenhao Yin3Shujun Zhao4Yan Zhang5Xin Zhao6The Second Hospital of Dalian Medical UniversityThe Second Hospital of Dalian Medical UniversityThe Affiliated Hospital of Liaoning University of Traditional Chinese MedicineLiaoning University of Traditional Chinese MedicineLiaoning University of Traditional Chinese MedicineThe Affiliated Hospital of Liaoning University of Traditional Chinese MedicineThe Second Hospital of Dalian Medical UniversityAbstract Chronic heart failure(HF) has become a disease of global concern due to its high morbidity and mortality.This has highlighted the need for cardioprotective agents.The Tonifying Kidney and Activating Blood(KTBA) decoction has been approved for clinical treatment of chronic HF.Tanshinone IIA(Tan IIA), rooted from Salvia miltiorrhiza of KTBA, has been approved for treating cardiovascular conditions.However, the mechanism is still unclear.This study examined the impact of KTBA on cardiomyocyte fibrosis in a rat model of heart failure post-myocardial infarction, induced by ligation of the left anterior descending coronary artery, followed by exhaustive swimming and starvation. Additionally, the effects of Tan IIA on CCD-841CoN cells were assessed under ischemic conditions in a 37 °C incubator with hypoxic environment (1% O2, 5% CO2, and 94% N2). The investigation employed an integrative approach combining network pharmacology with molecular mechanism analysis.The findings of network pharmacology indicate that KTBA may exert its influence by targeting key proteins such as TNF, AKT1, STAT3, RELA (NF-κB p65), NFκBIA (I-κBα), and MAPK14 (p38α).Results showed that KTBA increased SERCA2a level, lowered collagen I and III, α-SMA, and phospholamban levels, reduced collagen fiber deposition, and delayed mitochondria injury.This cardioprotection effect was perhaps due to suppressing the expressions of p38MAPK, I-κBα, NF-κB, AQP4,AKT, PI3K, TNF-α, and STAT3 and increasing the levels of ZO-1 and Occludin in hippocampus of chronic HF rats, which were partially diminished by SB203580 and PDTC.Additionally, Tan IIA reduced levels of p38MAPK, I-κBα, NF-κB, STAT3, and increased levels of AQP4, Claudin-1, ZO-1, and ZO-2,that were reduced by siRNAs targeting p38MAPK, NF-κB, and AQP4.In conclusion, by modulating the p38MAPK/NF-κB/AQP4 axis, KTBA decoction delays cardiomyocyte fibrosis through alleviating hippocampal blood-brain barrier and Tan IIA improves enterocyte barrier integrity.https://doi.org/10.1038/s41598-025-01276-9Chronic heart failureCardiac fibrosisTonifying kidney and activating blood DecoctionP38MAPK/NF-κB/AQP4 pathwayNetwork Pharmacology |
| spellingShingle | Rui Xu Yanping Bi Yetao Ju Wenhao Yin Shujun Zhao Yan Zhang Xin Zhao Uncovering the molecular mechanisms of tonifying kidney and activating blood Decoction against myocardial fibrosis using network Pharmacology and experimental validation Scientific Reports Chronic heart failure Cardiac fibrosis Tonifying kidney and activating blood Decoction P38MAPK/NF-κB/AQP4 pathway Network Pharmacology |
| title | Uncovering the molecular mechanisms of tonifying kidney and activating blood Decoction against myocardial fibrosis using network Pharmacology and experimental validation |
| title_full | Uncovering the molecular mechanisms of tonifying kidney and activating blood Decoction against myocardial fibrosis using network Pharmacology and experimental validation |
| title_fullStr | Uncovering the molecular mechanisms of tonifying kidney and activating blood Decoction against myocardial fibrosis using network Pharmacology and experimental validation |
| title_full_unstemmed | Uncovering the molecular mechanisms of tonifying kidney and activating blood Decoction against myocardial fibrosis using network Pharmacology and experimental validation |
| title_short | Uncovering the molecular mechanisms of tonifying kidney and activating blood Decoction against myocardial fibrosis using network Pharmacology and experimental validation |
| title_sort | uncovering the molecular mechanisms of tonifying kidney and activating blood decoction against myocardial fibrosis using network pharmacology and experimental validation |
| topic | Chronic heart failure Cardiac fibrosis Tonifying kidney and activating blood Decoction P38MAPK/NF-κB/AQP4 pathway Network Pharmacology |
| url | https://doi.org/10.1038/s41598-025-01276-9 |
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