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| Exploration of effect and mechanism of Shenlan Granule on transverse aortic constriction-induced heart failure in mice based on network pharmacology and experimental verification |
| Hits 706 Download times 281 Received:September 11, 2024 |
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| DOI
10.11656/j.issn.1672-1519.2025.02.14 |
| Key Words
Shenlan Granule;transverse aortic constriction;heart failure;network pharmacology |
| Author Name | Affiliation | E-mail | | LIU Yan | Cardiovascular Department, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China
Zhengzhou Hospital of Chinese Medicine, Zhengzhou 450046, China | | | CHEN Xiaoyan | Joint Formula and Syndrome Research Laboratory, Guangzhou University of Chinese Medicine & Zhengzhou Hospital of Chinese Medicine, Zhengzhou 450046, China
School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510405, China | | | ZHANG Li | Joint Formula and Syndrome Research Laboratory, Guangzhou University of Chinese Medicine & Zhengzhou Hospital of Chinese Medicine, Zhengzhou 450046, China
Henan Provincial Key Cardiovascular Disease Laboratory of Chinese Medicine, Zhengzhou 450046, China | 532825609@qq.com | | XU Xuegong | Joint Formula and Syndrome Research Laboratory, Guangzhou University of Chinese Medicine & Zhengzhou Hospital of Chinese Medicine, Zhengzhou 450046, China
Henan Provincial Key Cardiovascular Disease Laboratory of Chinese Medicine, Zhengzhou 450046, China
Henan Provincial Transformation Engineering Research Center of Chinese Medicine for Chronic Diseases, Zhengzhou 450046, China | xuxg1115@126.com |
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| Abstract
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| [Objective] The study aims to investigate the potential mechanism of Shenlan Granule（SLG） on heart failure（HF） via network pharmacology and animal experiments. [Methods] TCMSP，GeneCards，and BATMAN databases were used to screen the active ingredients and related targets of SLG for HF prevention. The protein-protein interaction network（PPI） and “drug-component-target” network were constructed using the STRING database and Cytoscape software. GO and KEGG enrichment analyses of the targets were performed by R-studio. The HF model was established by C57 mice using the transverse aortic constriction method. These mice were divided into sham surgery group，model group，low-dose SLG group，high-dose SLG group，and captopril group. After 4 weeks of continuous drug administration，echocardiography was used to detect ejection fraction（EF），fractional shortening rate（FS），left ventricular end-systolic internal diameter（LVIDs），and left ventricular end-diastolic internal diameter（LVIDs）. ELISA was used to detect the levels of pro-brain natriuretic peptide（NT-proBNP）and interleukin（IL）-6，IL-1β，and tumor necrosis factor α（TNF-α） in serum. HE staining was used to observe myocardial injury. Masson staining was used to observe the degree of myocardial fibrosis. WGA staining was used to observe the size of cardiomyocytes. The qPCR was used to detect the mRNA expression levels of serine/threonine protein kinase（AKT），nuclear factor κB（NF-κB），and IL-1β. Western blot was used to detect the protein expression of phosphatidylinositol 3-kinase（PI3K），p-PI3K，p-AKT，AKT，p-NF-κB，and NF-κB. [Results] AA total of 84 active ingredients were screened out from SLG. The key targets for the treatment of HF include IL-6，AKT1，STAT3，IL-1β，etc. GO analysis which obtained 2 841 items suggested that the potential targets that acted on biological processes were lipopolysaccharide reaction，active oxygen metabolism，and the regulation of blood vessel diameter，etc. KEGG analysis suggested that the related pathways were the PI3K/AKT signaling pathway，tumor necrosis signaling pathway，NF-κB signaling pathway，etc. Experimental results show that compared with the model group，SLG dose groups significantly decreased EF and FS（P<0.01），decreased LVIDd and LVIDs（P<0.05 or P<0.01），decreased the contents of NT-proBNP，IL-6，IL-1β and TNF-α in serum（P<0.05 or P<0.01），decreased the volume of myocardial collagen fibers（P<0.01），decreased the mean cross-sectional area of cells（P<0.05 or P<0.01），and decreased the mRNA expression levels of IL-1β，AKT and NF-κB（P<0.05 or P<0.01）. The ratio of p-PI3K/PI3K，p-AKT/AKT，and p-NF-κB/NF-κB protein was also decreased（P<0.01）. [Conclusion] SLG may exert cardioprotective effects on HF mice under pressure load by regulating the level of cardiac inflammation via the PI3K/AKT/NF-κB signaling pathway. |
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