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Si-Miao-Yong-An Decoction Protects Against Cardiac Hypertrophy and Dysfunction by Inhibiting Platelet Aggregation and Activation.

ABSTRACT: Objective: The aim of this study was to determine whether Si-Miao-Yong-An decoction (SMYAD) could ameliorate pressure overload-induced heart hypertrophy and its mechanisms. Methods: C57BL/6 mice were subjected to either sham or transverse aortic constriction (TAC) surgery to induce heart hypertrophy. SMYAD (14.85 g/kg/day, ig) or captopril (16.5 mg/kg/day, ig) was administered to the mice for 4 weeks. Cardiac function was evaluated based on echocardiography. Heart hypertrophy was detected using hematoxylin and eosin or wheat germ agglutinin staining. Protein expression of CD41, CD61, and P-selectin were measured with Western blot and immunohistochemistry. The expression levels of atrial natriuretic peptide, brain natriuretic peptide, ?-myosin heavy chain, ?-thromboglobulin, and von Willebrand factor were evaluated by quantitative polymerase chain reaction. Results: Four weeks after TAC, mice developed exaggerated cardiac hypertrophy and demonstrated a strong decrease in left ventricular ejection fraction compared with sham (29.9 ± 9.3% versus 66.0 ± 9.9%; P < 0.001). Conversely, SMYAD improved cardiac dysfunction with preserved left ventricular ejection fraction (66.5 ± 17.2%; P < 0.001). Shortening fraction was increased by SMYAD, while the left ventricular internal diameter and left ventricular volume were decreased in SMYAD group. SMYAD treatment significantly attenuated cardiac hypertrophy as reflected by the inhibition of atrial natriuretic peptide, brain natriuretic peptide, ?-myosin heavy chain mRNA expression, and by the decreasing of cardiac myocyte cross-sectional area. Furthermore, Western blot and immunohistochemistry indicated that the protein expression of platelet aggregation markers (CD41 and CD61) and platelet activation marker (P-selectin) were significantly higher in model mice compared with control. These pathological alterations in TAC-induced mice were significantly ameliorated or blocked by SMYAD administration. Conclusions: Our results suggested that SMYAD exerted its effect by inhibiting platelet aggregation and activation as revealed by CD41/CD61/P-selectin downregulation. Inhibition the activation of the platelets might contribute to the therapeutic effect of SMYAD in failing heart.

SUBMITTER: Su C

PROVIDER: S-EPMC6759602 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Si-Miao-Yong-An Decoction Protects Against Cardiac Hypertrophy and Dysfunction by Inhibiting Platelet Aggregation and Activation.

Su Congping C Wang Qing Q Zhang Huimin H Jiao Wenchao W Luo Hui H Li Lin L Chen Xiangyang X Liu Bin B Yu Xue X Li Sen S Wang Wei W Guo Shuzhen S

Frontiers in pharmacology 20190918

<b>Objective:</b> The aim of this study was to determine whether Si-Miao-Yong-An decoction (SMYAD) could ameliorate pressure overload-induced heart hypertrophy and its mechanisms. <b>Methods:</b> C57BL/6 mice were subjected to either sham or transverse aortic constriction (TAC) surgery to induce heart hypertrophy. SMYAD (14.85 g/kg/day, ig) or captopril (16.5 mg/kg/day, ig) was administered to the mice for 4 weeks. Cardiac function was evaluated based on echocardiography. Heart hypertrophy was d ...[more]

PMID: 31619988

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Project description:AimsWe assessed the efficacy of the traditional Chinese medicine formulation Jia-Wei-Si-Miao-Yong-An decoction (HJ11) in the treatment of acute coronary syndrome and evaluated its impact on the intestinal microbiota and their metabolites.MethodsAn acute coronary syndrome model was established in rats, which were randomly assigned to the model, HJ11 treatment, and atorvastatin treatment groups. Rats were then administered saline solution (model and sham operation control groups) or drugs by oral gavage for 28 d. Echocardiography was performed and serum creatine kinase-MB and cardiac troponin I levels were monitored to examine the cardiac function. Inflammation was evaluated using hematoxylin and eosin staining of heart tissue, and serum interleukin-2, interleukin-6, tumor necrosis factor alpha, and high-sensitivity C-reactive protein measurements. Gut microbiota composition was analyzed via 16S rRNA gene sequencing. Metabolomics was used to determine fecal metabolites and elucidate the modes of action of HJ11 in acute coronary syndrome treatment.ResultsHJ11 improved cardiac function and attenuated inflammation in rats with acute coronary syndrome. Relative to the untreated model group, the HJ11-treated group presented normalized Firmicutes/Bacteroidetes ratio and reduced abundances of the bacterial genera norank_f__Ruminococcaceae, Desulfovibrio, Clostridium_sensu_stricto_1, Adlercreutzia, Staphylococcus, Bacteroides, Prevotella, Rikenellaceae_RC9_gut_group, unclassified_o__Bacteroidales, and Ruminococcus_gauvreauii_group. We found 23 differentially expressed intestinal metabolites, and the enriched metabolic pathways were mainly related to amino acid metabolism. We also discovered that asymmetric dimethylarginine levels were strongly associated with cardiovascular disease. Correlation analyses revealed strong associations among intestinal microflora, their metabolites, proinflammatory factors, and cardiac function. Hence, the therapeutic effects of HJ11 on acute coronary syndrome are related to specific alterations in gut microbiota and their metabolites.ConclusionThis work demonstrated that HJ11 effectively treats acute coronary syndrome. HJ11 seems to increase the abundance of beneficial bacterial taxa (Bacteroides and Rikenellaceae_RC9_gut_group), mitigate the risk factors associated with cardiovascular disease, alter bacterial metabolites, lower asymmetric dimethylarginine levels, and effectively treat acute coronary syndrome.

Project description:ObjectiveModified Si-Miao-Yong-An decoction (MSMYA) was empirically originated from Si-Miao-Yong-An Decoction, which has been utilized for centuries to treat vasculopathy as well as heart diseases through clearing heat and detoxifying. This study aimed at confirming MSMYA's therapeutic effects for treating myocardial ischemia/reperfusion (I/R) injury and its underlying mechanisms.MethodsRats were intragastrically administered with MSMYA for 4 weeks after ischemia/reperfusion (I/R) operation. Superoxide dismutase (SOD) and malondialdehyde (MDA) concentration were determined by calorimetry. Coagulation function was determined using an automated coagulation analyzer. Levels of cysteinyl aspartate specific proteinase (caspase)-1, interleukin (IL)-1β, interleukin (IL)-18, and lactate dehydrogenase (LDH) were measured by an enzyme-linked immunosorbent assay (ELISA). Infarct size was determined by triphenyltetrazolium chloride (TTC) staining. Myocardial histopathological and ultrastructure changes were examined by H&E staining and electron microscopy, respectively. Relative mRNA expression of NLRP3, an apoptosis-associated speck-like proteins containing the caspase activation and recruitment domain (ASC), caspase-1, IL-1β, and IL-18 were analyzed using quantitative real-time polymerase chain reaction (PCR). Meanwhile, their relative protein expressions were measured using western blotting.ResultsThe results showed MSMYA can inhibit oxidative stress by increasing SOD and reducing MDA, suppress inflammatory reaction by decreasing NLRP3 inflammasome-related cytokines' level, improve coagulation function by increasing prothrombin time (PT) and activating partial thromboplastin time (APTT), and ameliorate myocardial histopathological and ultrastructural changes. In addition, MSMYA's cardioprotective effects probably related to suppressing NLRP3 inflammasome pathway activation by reducing NLRP3 inflammasome molecular mRNA and protein relative expression.ConclusionThe results indicated that MSMYA played an important role in protecting the myocardium from I/R injury. The likely mechanism is the inhibition of oxidative stress, improvement of cardiac injury, and the reduction of NLRP3-related inflammatory cytokines release. This provides a basis for further research on the mechanism and clinical application of MSMYA to improve myocardial I/R injury.

Project description:BackgroundAbdominal aortic aneurysm (AAA) is a fatal disease characterized by high morbidity and mortality in old population. Globally, effective drugs for AAA are still limited. Si-Miao-Yong-An decoction (SMYAD), a traditional Chinese medicine (TCM) formula with a high medical value, was reported to be successfully used in an old AAA patient. Thus, we reason that SMYAD may serve as a potential anti-AAA regime.ObjectiveThe exact effects and detailed mechanisms of SMYAD on AAA were explored by using the experimental study and bioinformatics analysis.MethodsFirstly, C57BL/6N mice induced by Bap and Ang II were utilized to reproduce the AAA model, and the effects of SMYAD were systematically assessed according to histology, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Then, network pharmacology was applied to identify the biological processes, pathways, and hub targets of SMYAD against AAA; moreover, molecular docking was utilized to identify the binding ability and action targets.ResultsIn an animal experiment, SMYAD was found to effectively alleviate the degree of pathological expansion of abdominal aorta and reduce the incidence of Bap/Ang II-induced AAA, along with reducing the damage to elastic lamella, attenuating infiltration of macrophage, and lowering the circulating IL-6 level corresponding to the animal study, and network pharmacology revealed the detailed mechanisms of SMYAD on AAA that were related to pathways of inflammatory response, defense response, apoptotic, cell migration and adhesion, and reactive oxygen species metabolic process. Then, seven targets, IL-6, TNF, HSP90AA1, RELA, PTGS2, ESR1, and MMP9, were identified as hub targets of SMYAD against AAA. Furthermore, molecular docking verification revealed that the active compounds of SMYAD had good binding ability and clear binding site with core targets related to AAA formation.ConclusionSMYAD can suppress AAA development through multicompound, multitarget, and multipathway, which provides a research direction for further study.

Dataset Information

Si-Miao-Yong-An Decoction Protects Against Cardiac Hypertrophy and Dysfunction by Inhibiting Platelet Aggregation and Activation.

Publications

Si-Miao-Yong-An Decoction Protects Against Cardiac Hypertrophy and Dysfunction by Inhibiting Platelet Aggregation and Activation.

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