Centella asiatica (L.) Urb. attenuates cardiac hypertrophy and improves heart function through multi-level mechanisms revealed by systems pharmacology

Ding, Bojiao; Niu, Weihong; Wang, Siyi; Zhang, Fan; Wang, Haiqing; Chen, Xuetong; Chen, Sen; Ma, Shuangxin; Kang, Wenhui; Wang, Mingjuan; Liang, Li; Xiao, Wei; Guo, Zihu; Wang, Yonghua

doi:10.1016/j.jep.2022.115106

Cited by 8 publications

(3 citation statements)

References 44 publications

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“…The targets with Inference Score greater than or equal to 200 were selected from the CTD (http://ctd.Mdibl.Org/) database as anti‐MI drug targets, and the database of MI‐related targets was established by combining literature mining methods (Ding et al, 2022). The aforementioned SP targets were compared with those related to MI, and the predicted targets for the treatment of MI were summarized to establish a library of SP anti‐MI targets.…”

Section: Methodsmentioning

confidence: 99%

Establishment of fingerprint and mechanism of anti‐myocardial ischemic effect of Syringa pinnatifolia

Zhang

et al. 2022

Biomedical Chromatography

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This study established the fingerprint of Syringa pinnatifolia Hemsl. (SP), analyzed the SP ingredients absorbed into the rats blood, and evaluated its anti-myocardial ischemic effect to provide a scientific basis for the follow-up development and research of SP and lay a foundation for its clinical application using ultra-performance liquid chromatography-Q Exactive-mass spectrometry and GC-MS. Myocardial infarction was induced in rat by ligating the left anterior descending branch of the rat coronary artery, and SP alcohol extract was administered to evaluate its anti-myocardial ischemic effect. We analyzed the SP ingredients absorbed into the rats blood, screened the active compounds, established a database of SP anti-myocardial ischemic targets, and explored the possible mechanism of SP in treating myocardial infarction using bioinformatics. The rats were examined using echocardiography, serum biomarkers were determined, and pathological changes were observed by histopathological examination. TUNEL staining was performed to detect the apoptotic level of cells, and Western blot and quantitative real-time polymerase chain reaction were performed to detect the expression levels of Bcl-2, Bax, and Caspase-3 in heart tissues.In the fingerprint of SP, 24 common peaks were established, and the similarity evaluation results of 10 batches of SP were all >0.9. Ultra-performance liquid chromatography-Q Exactive-mass spectrometry and GC-MS detected 17 active ingredients in the drug-containing serum, including terpenoids, flavonoids, phenols, phenylpropanoids, and phenolic acids, the most abundant of which was resveratrol.Enrichment analysis of SP targets against myocardial ischemia revealed that key candidate targets of SP were significantly enriched in multiple pathways associated with apoptosis. Resveratrol was administered to the successfully modeled rats, and the results showed that the resveratrol group significantly decreased left ventricular enddiastolic diameter and left ventricular end-systolic diameter and significantly increased ejection fraction and fractional shortening in all groups compared with the model group. Resveratrol significantly decreased the levels of creatine kinase isoenzyme and lactate dehydrogenase in serum compared to the model group (P < 0.001).Hematoxylin-eosin staining of rat myocardial tissue showed that all lesions were reduced under microscopic observation in the resveratrol group compared with the model group. Real-time polymerase chain reaction and Western blot results showed

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Section: Methodsmentioning

confidence: 99%

Establishment of fingerprint and mechanism of anti‐myocardial ischemic effect of Syringa pinnatifolia

Zhang

et al. 2022

Biomedical Chromatography

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“…Some studies used the method of network pharmacology to explore the potential therapeutic targets and biological mechanisms of CA in the treatment of fibrotic disorders, but only one or six compounds were involved [ 12 , 13 , 14 ]. In addition, through the combination of network pharmacological prediction and experimental verification, it was reported in the literature that CA can improve cardiac hypertrophy, hypertrophic scar, and liver injury [ 15 , 16 , 17 ]. The study of network pharmacology regarding CA involved very few components and has not yet been applied to an anti-angiogenesis activity.…”

Section: Introductionmentioning

confidence: 99%

Uncovering the Anti-Angiogenic Mechanisms of Centella asiatica via Network Pharmacology and Experimental Validation

Zhao,

Li,

Wang

et al. 2024

Molecules

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Background: Centella asiatica (CA) has been used to address cancer for centuries in traditional Chinese medicine (TCM). Previous studies demonstrated its anti-angiogenesis efficacy, but the underlying mechanism of its action remains to be further clarified. This study aims to investigate the underlying mechanisms of CA and its triterpenes in anti-angiogenesis for cancer therapeutics through network pharmacology and experimental validation. Methods: Cytoscape was used to construct a network of compound–disease targets and protein–protein interactions (PPIs) from which core targets were identified. GO and KEGG analyses were performed using Metascape, and the AutoDock-Vina program was used to realize molecular docking for further verification. Then, VEGF165 was employed to establish an induced angiogenesis model. The anti-angiogenic effects of CA were evaluated through assays measuring cell proliferation, migration, and tubular structure formation. Results: Twenty-five active ingredients in CA had potential targets for anti-angiogenesis including madecassoside, asiaticoside, madecassic acid, asiatic acid, and asiaticoside B. In total, 138 potential targets for CA were identified, with 19 core targets, including STAT3, SRC, MAPK1, and AKT1. A KEGG analysis showed that CA is implicated in cancer-related pathways, specifically PD-1 and AGE-RAGE. Molecular docking verified that the active components of CA have good binding energy with the first four important targets of angiogenesis. In experimental validation, the extracts and triterpenes of CA improved VEGF165-induced angiogenesis by reducing the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Conclusions: Our results initially demonstrate the effective components and great anti-angiogenic activity of CA. Evidence of the satisfactory anti-angiogenic action of the extracts and triterpenes from CA was verified, suggesting CA’s significant potential as a prospective agent for the therapy of cancer.

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“…empty pods [ 14 ], Plantago asiatica L. seeds [ 15 ], and Centella asiatica (L.) Urb. [ 16 ] were demonstrated to decrease cardiac hypertrophy.…”

Section: Introductionmentioning

confidence: 99%

Parkia speciosa Hassk. Empty Pod Extract Prevents Cardiomyocyte Hypertrophy by Inhibiting MAPK and Calcineurin-NFATC3 Signaling Pathways

Mustafa

Jalil

Saleh

et al. 2022

Life

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Cardiac hypertrophy is an early hallmark during the clinical course of heart failure. Therapeutic strategies aiming to alleviate cardiac hypertrophy via the mitogen-activated protein kinase (MAPK)/calcineurin-nuclear factor of activated T-cells (NFAT) signaling pathway may help prevent cardiac dysfunction. Previously, empty pod ethanol crude extract of Parkia speciosa Hassk was shown to demonstrate protective effects against cardiomyocyte hypertrophy. Therefore, the current study aimed to investigate the effects of various fractions of the plant ethanol extract on the MAPK/NFAT signaling pathway in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. Simultaneous treatment with ethyl acetate (EA) fraction produced the most potent antihypertrophic effect evidenced by the reduced release of B-type natriuretic peptide (BNP). Subsequently, treatment with the EA fraction (6.25, 12.5, and 25 μg/mL) prevented an Ang II-induced increase in cell surface area, hypertrophic factors (atrial natriuretic peptide and BNP), reactive oxygen species, protein content, and NADPH oxidase 4 expression in the cells. Furthermore, EA treatment attenuated the activation of the MAPK pathway and calcineurin-related pathway (GATA-binding protein 4 and NFATC3), which was similar to the effects of valsartan (positive control). Our findings indicate that the EA fraction prevents Ang II-induced cardiac hypertrophy by regulating the MAPK/calcineurin-NFAT signaling pathway.

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Centella asiatica (L.) Urb. attenuates cardiac hypertrophy and improves heart function through multi-level mechanisms revealed by systems pharmacology

Cited by 8 publications

References 44 publications

Establishment of fingerprint and mechanism of anti‐myocardial ischemic effect of Syringa pinnatifolia

Establishment of fingerprint and mechanism of anti‐myocardial ischemic effect of Syringa pinnatifolia

Uncovering the Anti-Angiogenic Mechanisms of Centella asiatica via Network Pharmacology and Experimental Validation

Parkia speciosa Hassk. Empty Pod Extract Prevents Cardiomyocyte Hypertrophy by Inhibiting MAPK and Calcineurin-NFATC3 Signaling Pathways

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