[Pathogenesis of chronic heart failure in rats based on ferroptosis-mediated oxidative stress and intervention effect of Shenfu Injection].

This study aims to investigate the pathogenesis of chronic heart failure based on ferroptosis-mediated oxidative stress and predict the targets of Shenfu Injection in treating chronic heart failure. A rat model of chronic heart failure was established by the isoproterenol induction method. According to the random number table method, the modeled rats were assigned into three groups: a model group, a Shenfu Injection group, and a ferrostatin-1(ferroptosis inhibitor) group. In addition, a normal group was designed. After 15 days of intervention, the cardiac mass index and left ventricular mass index were determined. Echocardiography was employed to eva-luate the cardiac function. Hematoxylin-eosin staining and Masson staining were employed to reveal the pathological changes and fibrosis of the heart, and Prussian blue staining to detect the aggregation of iron ions in the myocardial tissue. Transmission electron microscopy was employed to observe the mitochondrion ultrastructure in the myocardial tissue. Colorimetry was adopted to measure the levels of iron metabolism, lipid peroxidation, and antioxidant indicators. Flow cytometry was employed to measure the content of lipid-reactive oxygen species(ROS) and the fluorescence intensity of ROS. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of ferroptosis-related factors in the myocardial tissue. The results showed that the rats in the model group had reduced cardiac function, elevated levels of total iron and Fe~(2+), lowered level of glutathione(GSH), increased malondialdehyde(MDA), decreased superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px), and rising levels of ROS and lipid-ROS. In addition, the model group showed fibrous tissue hyperplasia with inflammatory cell infiltration and myocardial fibrosis, iron ion aggregation, and characteristic mitochondrial changes specific for iron death. Moreover, the model group showcased upregulated protein and mRNA levels of p53 and COX2 and downregulated protein and mRNA levels of GPX4, FTH1, SLC7A11, and Nrf2 in the myocardial tissue. The intervention with Shenfu Injection significantly improved the cardiac function, recovered the iron metabolism, lipid peroxidation, and antioxidant indicators, decreased iron deposition, improved mitochondrial structure and function, and alleviated inflammatory cell infiltration and fibrosis. Furthermore, Shenfu Injection downregulated the mRNA and protein levels of p53 and COX2 and upregulated the mRNA and protein levels of GPX4, FTH1, SLC7A11, and Nrf2 in the myocardial tissue. Shenfu Injection can improve the cardiac function by regulating iron metabolism, inhibiting ferroptosis, and reducing oxidative stress injury.

[Protective effect of Shenfu Injection on regulation of autophagy in rats with chronic heart failure based on PI3K/Akt/mTOR pathway].

This study aimed to investigate the mechanism and target sites of Shenfu Injection in the intervention of chronic heart fai-lure based on the PI3K/Akt/mTOR autophagy signaling pathway. The chronic heart failure model was induced in rats by subcutaneous injection of isoproterenol. The model rats were randomly divided into model group, Shenfu Injection group, and 3-methyladenine autophagy inhibitor(3-MA) group. A normal group was also set up. After 15 days of administration, cardiac function indexes of the rats were detected by echocardiography. The serum N-terminal pro-B-type natriuretic peptide(NT-proBNP) levels were measured using the ELISA. HE and Masson staining was performed to observe the morphological changes in myocardial tissues, and electron microscopy was used to observe the autophagosomes in myocardial tissues. Western blot was conducted to measure the changes in autophagy-related proteins(LC3 Ⅱ/Ⅰ and p62), PI3K, Akt, mTOR, and phosphorylation levels. The results showed that compared with normal group, model group in rats led to reduced cardiac function, significant activation of cardiac autophagy, increased fibrotic lesions in myocardial tissues, structural disorder of the myocardium, increased autophagosomes, and cytoplasmic vacuolization. Compared with model group, Shenfu Injection group in rats led to cardiac function significantly improved, myocardial fibrosis decreased, and the number of autophagosomes and cytoplasmic vacuolization decreased. The phosphorylation levels of PI3K, Akt, and mTOR were significantly increased(P<0.01). In the 3-MA group, autophagy was inhibited through the activation of the PI3K/Akt/mTOR signaling pathway, resulting in improved cardiac function, reduced myocardial fibrosis, and no significant cytoplasmic vacuolization. The findings suggest that Shenfu Injection can activate the PI3K/Akt/mTOR signaling pathway and inhibit autophagy, thereby improving cardiac function.

[Research trends and hot spots of Chuanxiong Rhizoma from 2010 to 2023].

This study aims to objectively and quantitatively analyze the research status and hot spots of Chuanxiong Rhizoma and provide guidance for further research and clinical application of this herbal medicine. Firstly, the research articles involving Chuanxiong Rhizoma from 2010 to 2023 were retrieved from seven databases including Web of Science, PubMed, Medline, CNKI, VIP, Wanfang, and SinoMed. Then, NoteExpress and manual reading were employed to complete the de-duplication and screening of the articles, and the annual number of publications and journals was analyzed. Finally, CiteSpace was used for systematic analysis of the research institutions, authors, and keywords, and the corresponding knowledge maps were established. After screening, 1 137 articles in Chinese and 433 articles in English were included, and the annual number of publications showed an increasing trend. Chinese Journal of Experimental Traditional Medical Formulae and Journal of Ethnopharmacology were the top Chinese and English journal in the number of publications. Chengdu University of Traditional Chinese Medicine and Nanjing University of Chinese Medicine published the most articles in Chinese and English, respectively. PENG Cheng and FENG Yi were the authors published more articles in Chinese and English. Ferulic acid, signaling pathway, mechanism, headache, ligustrazine, and apoptosis were frequent keywords. A total of 20 clusters and 30 bursts were generated. The comprehensive analysis showed that the research trends and hot spots in this field mainly focused on pharmacological components and isolation, pharmacological effects and mechanism, clinical application and efficacy, compatibility and efficacy of drug pairs, quality evaluation and control, and cultivation and germplasm improvement.

[Mechanism of ferroptosis in chronic heart failure based on theory of "harmful hyperactivity and responding inhibition"].

Chronic heart failure is the end stage of heart diseases caused by multiple causes. Myocardial cell injury is the key cause of cardiac function deterioration. Ferroptosis, an iron-dependent programmed death mode, is characterized by iron overload and excessive accumulation of lipid peroxides. Studies have demonstrated that inhibiting ferroptosis has a protective effect on myocardial cells. The theory of "harmful hyperactivity and responding inhibition" is an important rule developed by physicians to explain the generation and restriction of the five elements and the pathological imbalance of the human body, and can guide medication. Correlating with the nature, humans need to rely on the law of responding inhibition to maintain the harmony of five Zang-organs and the steady state of Fu-organs. The pathogenesis of ferroptosis in chronic heart failure highly coincides with the process of failing to "inhibition and hyperactivity becoming harmful". The initial factor of ferroptosis is the deficiency of heart Qi, which results in the inability to maintain the balance of cardiomyocyte redox system. The involvement of the five Zang-organs leads to the loss of distribution of body fluid and blood. As a result, the phlegm turbidity, blood stasis, and water retention in the meridians occur, which are manifested as the accumulation of iron and lipid peroxides, which is the aggravating factor of ferroptosis. The two factors interact with each other, leading to the spiral development and thus aggravating heart failure. According to the traditional Chinese medicine(TCM) pathogenesis of ferroptosis, the authors try to treat the chronic heart failure by stages in accordance with the general principle of restraining excess and alleviating hyperactivity. The early-stage treatment should "nourish heart Qi, regulate the five Zang-organs, so as to restrain excess". The middle-stage treatment should "active blood, resolve phlegm, dispel pathogen, and eliminate turbidity", so as to alleviate hyperactivity. The late-stage treatment should "warm Yang, replenish Qi, active blood, and excrete water". Following the characteristics of pathogenesis, the TCM intervention can reduce iron accumulation and promote the clearance of lipid peroxide, thus inhibiting ferroptosis and improving cardiac function.

A bibliometric and visual analysis of research trends and hotspots of myocardial apoptosis: A review.

BACKGROUND: Recent studies have found that cardiomyocyte apoptosis is closely associated with the pathophysiological development of various cardiovascular diseases, for example chronic heart failure and myocardial infarction. At present, there are many researches in this field, such as pharmacological research, traditional Chinese medicine intervention research and pathway research. However, the relevant research is fragmented, with few comprehensive analysis and systematic combing. METHODS: The relevant literature on cardiomyocyte apoptosis was downloaded from the Web of Science Core Collection (WoSCC) and PubMed databases. Citespace 6.1.R2 software Microsoft Excel 2019 and VOSviewer1.6.18.0 were used for bibliometric and visual analysis of publication volume, countries, institutions, journals, authors, keywords. RESULTS: Since 1996, there are 1881 research articles and reviews related to cardiomyocyte apoptosis published by 10,313 researchers from 1648 institutions in 58 countries or regions were included. The number of annual publications showed an upward trend, especially in recent years. Countries participating in this research area include China, the United States, and Japan. Capital Medical University, Harbin Medical University are the key research institution, and other institutions also have substantial contribution on the project as to cardiomyocyte apoptosis. The journal EUR REV MED PHARMACO has a large number of publications, whereas CIRCULATION has the highest number of co-citations. Keywords analysis showed that apoptosis, expression and oxidative stress had higher frequencies, leading to 8 clusters. CONCLUSIONS: Cardiomyocyte apoptosis is a hot research field in recent years. Through visualization and bibliometric analysis, it is found that this field focus on hotspots like clinical manifestations including heart failure or myocardial infarction, and microscopic mechanisms such as oxidative stress and inflammation.

Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-ß 1/Smad Pathway Regulation.

OBJECTIVE: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. METHODS: Salt-sensitive (Dahl/SS) rats were fed with normal diet (0.3% NaCl) and the high-salt diet (8% NaCl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats (SS-13BN) were fed with the high-salt diet (8% NaCl) as the negative control group. After modeling, the model rats were randomly divided into heart failure (HF) group, Shenmai Injection (SMI) group and pirfenidone (PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay (ELISA), hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis. RESULTS: After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were significantly reduced, and the serum NT-proBNP concentration increased significantly (all P<0.05); furthermore, the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased (P<0.05); the protein and mRNA expressions of collagen type I (Col I) were up-regulated (P<0.05), and the mRNA expressions of transforming growth factor ß 1 (TGF- ß 1), Smad2 and Smad3 were significantly up-regulated (P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly (P<0.05), and the mRNA expressions of Col I, TGF- ß 1, Smad2 and Smad3, as well as Col I protein expression, were all significantly down-regulated (all P<0.05). CONCLUSION: Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-ß 1/Smad signaling pathway.

[Shenfu Injection improves chronic heart failure by regulating pyroptosis based on NLRP3/caspase-1 pathway].

This study investigated the mechanisms and targets of Shenfu Injection in the intervention in chronic heart failure(CHF) through the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/caspase-1 signaling pathway. A CHF model was induced in rats by subcutaneous injection of isoproterenol. Model rats were randomly divided into a model group, a Shenfu Injection group, and a MCC950(NLRP3 inhibitor) group, and a blank group was also set up as a control. After 15 days of treatment, echocardiography was performed to measure cardiac function parameters [left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS)]. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP), interleukin(IL)-1ß, and IL-18. Hematoxylin-eosin(HE) and Masson staining were used to observe morphological changes in myocardial tissues, and Western blot was used to measure the expression levels of NLRP3/caspase-1 pathway-related proteins [NLRP3, caspase-1, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), IL-1ß, and IL-18]. The study found that isoproterenol-induced CHF in rats resulted in decreased cardiac function, worsened myocardial fibrosis, increased expression levels of NLRP3, ASC, caspase-1, GSDMD-N, IL-1ß, and IL-18 in myocardial tissues, elevated serum inflammatory factors, and induced myocardial cell pyroptosis. Following Shenfu Injection intervention, the Shenfu Injection group showed significantly improved LVEF and LVFS, a significant decrease in NT-proBNP, a marked downregulation of NLRP3, ASC, caspase-1, GSDMD-N, IL-1ß, and IL-18 protein expression levels, reduced serum inflammatory factors IL-1ß and IL-18 expression in CHF rats, and a decrease in the rate of TUNEL-positive cells. Shenfu Injection can significantly improve cardiac function in CHF, inhibit myocardial fibrosis, and alleviate the progression of myocardial cell pyroptosis through the inhibition of the NLRP3/caspase-1 pathway.

[Protective effect of Shenfu Injection on rats with chronic heart failure based on HMGB1/TLR4/NF-κB signaling pathway].

The study aimed to explore the mechanism and targets of Shenfu Injection in the regulation of inflammatory injury in chronic heart failure rats based on the high mobility group box-1/Toll like receptor 4/nuclear factor kappa-B(HMGB1/TLR4/NF-κB) signaling pathway. The rat model of chronic heart failure was established using isoproterenol. The modeled rats were divided into three groups by random number table: the model group, Shenfu group and glycopyrrolate group, and the normal group was also set. The rats were administrated for 15 consecutive days, and on the following day after the last administration, they were sacrificed for sample collection. The cardiac mass index and left ventricular mass index of the rats in each group were measured, and the echocardiogram was used to analyze the cardiac function indices, and ELISA to test the inflammatory indices in rat serum. The pathological morphology and fibrosis status of rat heart tissues were observed by HE staining and Masson staining, respectively. The content of HMGB1 was determined by immunofluorescence staining. The protein and mRNA expression of HMGB1/TLR4/TLR4 signaling pathway was detected by Western blot and RT-qPCR, respectively. The results showed that the chronic heart failure rat model was successfully prepared. The rats in the model group had reduced cardiac function, increased levels of HMGB1 and inflammatory factors(P<0.05), and elevated protein and mRNA expression of HMGB1, TLR4, MyD88, and NF-κB P65 in myocardial tissue(P<0.05), with fibrous connective tissue hyperplasia, inflammatory cell infiltration and severe fibrosis. Shenfu Injection improved cardiac function, decreased the levels of HMGB1 and inflammatory factors(P<0.05) and the protein and mRNA expression of HMGB1, TLR4, MyD88, and NF-κB P65 in myocardial tissue(P<0.05), ameliorated interstitial fibrous connective tissue hyperplasia and inflammatory cell infiltration, and reduced fibrosis. In conclusion, Shenfu Injection can reduce inflammatory damage and improve cardiac function in chronic heart failure rats by regulating the HMGB1/TLR4/NF-κB signaling pathway.

Effect of Traditional Chinese Medicine on the Cardiovascular Diseases.

Background: Traditional Chinese medicine (TCM) is the health care system developed with the help of clinical trials that are based ideally on the scientific model of regulation. Objective: This systematic health care system relies on some specific unique theories and practical experiences to treat and cure diseases, thus enhancing the public's health. Review Methodology: The current review covers the available literature from 2000 to 2021. The data was collected from journals research articles, published books, thesis, and electronic databases, search engines such as Google Scholar, Elsevier, EBSCO, PMC, PubMed, ScienceDirect, Willey Online Library, Springer Link, and CNKI) searching key terms, cardiovascular disease, traditional Chinese medicines, natural products, and bioactive compounds. Full-length articles and abstracts were screened for the collection of information included in the paper. Results: Clinical trials on the TCM and basic research carried out on its mechanism and nature have led to the application and development of the perfect design of the research techniques, for example, twofold striking in acupuncture that aid in overcoming the limitations and resistances in integrating and applicability of these experiences and trials into the pre-existing biomedical models. Furthermore, TCM has also been utilized from ancient times to treat heart diseases in Asia, particularly in China, and is now used by people in many other areas. Cardiovascular disease (CVD) is mainly developed by oxidative stress. Hence antioxidants can be beneficial in treating this particular disease. TCM has a wide variety of antioxidant components. Conclusion: The current review article summarizes the underlying therapeutic property of TCM and its mechanism. It also overviews the evidence of the mechanism of TCM action in CVD prevention by controlling oxidative stress and its signaling pathway.

Bacterial diversity in the intestinal mucosa of heart failure rats treated with Sini Decoction.

BACKGROUND: Sini Decoction (SND), a classic Chinese medicine prescription, has been proved to have a good effect on heart failure (HF), whereas its underlying mechanism is still unclear. In order to explore the therapeutic mechanism of SND, we combined with 16S rRNA gene sequencing to analyze the composition of gut microflora in rats with HF. MATERIAL AND METHODS: Twenty Sprague-Dawley (SD) rats were divided into four groups (n = 5): normal group, model group, SND treatment group (SNT group), and metoprolol (Met) treatment group (Meto group). All the rats except the normal group were intraperitoneally injected with doxorubicin (concentration 2 mg/mL, dose 0.15 mL/100 g) once a week to induce HF. After successfully modeling, SND and Met were gavaged to rats, respectively. After the treatment period, blood was collected for hematological analyses, myocardial tissue and colon tissues were collected for Hematoxylin-Eosin (H&E) staining, and mucosal scrapings were collected for Illumina Miseq high-throughput sequencing. RESULTS: Echocardiographic results suggested that both left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) in Model rats decreased compared with normal rats. The results of H&E staining showed that compared with the model group, the structures of myocardial tissue and colon tissue in the SNT group and Meto group showed a recovery trend. Alpha results showed that the model group had higher species diversity and richness compared with the normal group. After treatment, the richness and diversity of intestinal bacteria in the SNT group were significantly restored, and Met also showed the effect of adjusting bacterial diversity, but its effect on bacterial richness was not ideal. At the Family level, we found that the number of several bacteria associated with HF in the model group increased significantly. Excitingly, SND and Met had shown positive effects in restoring these HF-associated bacteria. Similarly, the results of Linear discriminant analysis (LDA) showed that both SND and Met could reduce the accumulation of bacteria in the model group caused by HF. CONCLUSION: Collectively, SND can improve HF by regulating the intestinal flora. This will provide new ideas for the clinical treatment of patients with HF.

Identification and Comparison of Potential Biomarkers by Proteomic Analysis in Traditional Chinese Medicine-Based Heart Failure Syndromes.

Heart failure (HF) is an epidemic disease affecting a large population worldwide. Traditional Chinese medicine (TCM) is playing an increasingly important role in the clinical treatment of HF. According to the TCM theory, HF could be classified into Yang deficiency and Qi-yin deficiency; however, there are few objective and biological lines of evidence for differentiation of TCM HF syndromes to date. In this study, data-independent acquisition (DIA) mass spectrometry was applied to comparatively analyze the protein expression in serum samples obtained from 12 Yang deficiency patients, 12 Qi-yin deficiency patients, and 12 healthy volunteers. Compared to the healthy controls, a total of 121 differentially expressed proteins (DEPs) (77 upregulated and 44 downregulated proteins) were identified in Yang deficiency samples, while 59 DEPs (49 upregulated and 10 downregulated proteins) were detected in Qi-yin deficiency samples. Enrichment analyses of these DEPs based on the GO and KEGG databases revealed functional clusters associated with the immune system, signal transduction, and infectious disease. Several previously reported HF biomarker proteins were found to be the hub proteins in a protein-protein interaction network analysis. Three novel hub DEPs were identified as potential biomarkers for differentiation between different TCM syndromes of HF. The results provide biological insight into the differences of different TCM HF syndromes and an opportunity for specific biomarker identification for different TCM HF syndromes.

Test-Retest Reliability of the Coronary Heart Disease Damp Phlegm and Blood Stasis Pattern Questionnaire: Results from a Multicenter Clinical Trial.

BACKGROUND: Damp phlegm and blood stasis pattern (DPBSP) is the main pattern in coronary heart disease (CHD) patients. To quantify and standardize the diagnosis of DPBSP, questionnaires are usually administered. The CHD Damp Phlegm and Blood Stasis Pattern Questionnaire (CHD-DPBSPQ) is the standard metric for measuring CHD-DPBSP signs and symptoms in practice and clinical research. The CHD-DPBSPQ has moderate diagnostic efficiency, as evidenced by its receiver operating characteristic curves. Furthermore, and high reliability and validity have been shown in some studies but not in a multicenter clinical trial. Our purpose was to evaluate the test-retest reliability of a proprietary CHD-DPBSPQ. METHODS: The CHD-DPBSPQ uses a standard procedure for measuring symptoms. The (interrater) reliability and validity of this questionnaire have been previously studied. Here, we evaluated the test interval and weighted kappa value of items of test-retest (intrarater) reliability of the CHD-DPBSPQ. The test-retest reliability was evaluated by the intraclass correlation coefficient (ICC) for the total CHD-DPBSPQ score and the phlegm domain and blood stasis domain scores. Weighted kappa statistics were calculated for the individual CHD-DPBSPQ items. RESULTS: Using the CHD-DPBSPQ, 79 patients with late-stage CHD who were participating in a multicenter clinical trial were assessed twice. The ICCs for the CHD-DPBSPQ score were as follows: 0.827 for the total CHD-DPBSPQ, 0.778 for the phlegm domain score, and 0.828 for the blood stasis domain score. The reliability was slightly better in patients whose test interval was ≤14 days. The weighted kappa values of individual items showed moderate consistency. CONCLUSIONS: The CHD-DPBSPQ was found to have excellent test-retest reliability in this sample of patients.

[Animal model analysis of rheumatoid arthritis based on clinical characteristics of Chinese and Western medicine].

Rheumatoid arthritis(RA) is an autoimmune disease involving multiple joints bilaterally with symmetrical polyarthritis as the main symptom. The high disability rate of this disease seriously affects the quality of life of patients and even threatens their lives. The establishment of a good animal model is of great significance for the diagnosis and clinical prevention of RA. Based on the clinical characteristics of RA in traditional Chinese and Western medicine, the common animal models of RA were summarized, including drug-induced, gene-related, and syndrome and disease combined models. Joint swelling, pain, redness, nodules, and joint deformity are the main criteria for model evaluation, which have certain differences from the clinical diagnostic criteria of RA. From the perspective of syndrome differentiation, the animal model combining syndrome and disease only simulates the syndrome of traditional Chinese medicine and has no direct causal relationship with the formation of RA. In this paper, we analyzed the advantages and disadvantages of animal models of RA and the coincidence degree of the models with the clinical characteristics and then put forward the corresponding recommendations for the evaluation and improvement of these models, aiming to make the animal models of RA closer to the clinical symptoms and play an important role in the clinical diagnosis and treatment of RA.

Exploring the Molecular Mechanism of Action of Yinchen Wuling Powder for the Treatment of Hyperlipidemia, Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

BACKGROUND: Yinchen Wuling powder is often used to treat clinical hyperlipidemia, although its mechanism of action remains unclear. In this study, we aimed to investigate the active ingredients found in Yinchen Wuling powder and find its mechanism of action when treating hyperlipidemia, using a combination of network pharmacology, molecular docking, and molecular dynamics simulation approaches. METHODS: The TCMSP database was used to obtain the principle active ingredients found in Yinchen Wuling powder and the NCBI and DisGeNet databases were used to obtain the main target genes involved in hyperlipidemia, and the intersectional targets were obtained by EXCEL. We also used Cytoscape 3.7.2 software to construct a "Traditional Chinese Medicine-Active Ingredient-Target" network and use STRING platform to conduct "protein-protein interactional" (PPI) analyses on the intersection targets. Bioconductor software and RX 64 4.0.0 software were then used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis on the targets. Molecular docking of core protein-ligand interactions was modeled using AutoDock Vina software. A simulation of molecular dynamics was conducted for the optimal core protein-ligand obtained by molecular docking using Amber18 software. RESULTS: A total of 63 active ingredients were found in Yinchen Wuling powder, corresponding to 175 targets, 508 hyperlipidemia targets, and 55 intersection targets in total. Cytoscape 3.7.2 showed that the key active ingredients were quercetin, isorhamnetin, taxifolin, demethoxycapillarisin, and artepillin A. The PPI network showed that the key proteins involved were AKT1, IL6, VEGFA, and PTGS2. GO enrichment analysis found that genes were enriched primarily in response to oxygen levels and nutrient levels of the vesicular lumen and were associated with membrane rafts. These were mainly enriched in AGE-RAGE (advanced glycation end products-receptor for advanced glycation end products) signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis, as well as other pathways. The molecular docking results indicated key binding activity between PTGS2-quercetin, PTGS2-isorhamnetin, and PTGS2-taxifolin. Results from molecular dynamics simulations showed that PTGS2-quercetin, PTGS2-isorhamnetin, and PTGS2-taxifolin bound more stably, and their binding free energies were PTGS2-quercetin -29.5 kcal/mol, PTGS2-isorhamnetin -32 kcal/mol, and PTGS2-taxifolin -32.9 kcal/mol. CONCLUSION: This study is based on network pharmacology and reveals the potential molecular mechanisms involved in the treatment of hyperlipidemia by Yinchen Wuling powder.

[Analysis of animal models of hypertension based on characteristics of clinical symptoms of Chinese and western medicine].

Hypertension, a cardiovascular disease with main clinical manifestations of dizziness and elevated blood pressure, especially elevated arterial pressure, features high prevalence rate and low control rate, which affects patients' quality of life. Therefore, establishing a good animal model of hypertension is of great significance for its diagnosis and clinical prevention and treatment. Based on the clinical characteristics of hypertension in traditional Chinese and western medicine, this study summarized the advantages and disadvantages of current hypertension animal models: gene-related model, surgery-caused model, drug-induced model, and environment-induced model, and investigated the similarity to the clinical symptoms in traditional Chinese medicine and Western medicine. Among them, spontaneously hypertensive rats, models established with the surgical two-kidney one-clip, one-kidney one-clip, two-kidney two-clip, and abdominal aorta constriction methods, models induced with the drug deoxycorticosterone acetate, and models induced with the high-fat high-purine diet showed symptoms highly similar to the clinical manifestations. Then, the corresponding evaluation and improvement methods of hypertension animal models were proposed. This study provides suggestions for the establishment of hypertension animal model so that the symptoms are more similar to the clinical characteristics of hypertension in traditional Chinese and Western medicine, which is important for the clinical diagnosis and treatment of hypertension.

Cross-Talk between Gut Microbiota and the Heart: A New Target for the Herbal Medicine Treatment of Heart Failure?

Heart failure (HF) is the severe and terminal stage of various heart diseases. A growing number of studies have suggested the potential clinical significance of gut microbiota in the pathophysiology of HF. Herbal medicine (HM) plays a role in rebalancing the composition of gut microbiota and is widely used in the prevention and treatment of HF. There are many similarities between intestinal microecology and the traditional Chinese medicine (TCM) theory, such as the holistic concept and the theory of the "heart's connection with the small intestine." These similarities provide a theoretical basis for HM to prevent and treat diseases by regulating the intestinal flora and its metabolites. In this work, the cross-talk between gut microbiota and the heart is reviewed, and the relationship between TCM and gut microbiota is discussed. Based on the current literature and research, we hypothesize that the cross-talk between gut microbiota and the heart may offer a new therapeutic target for HF intervention.

[Research on Dynamic Evolution of Blockade of Heart Vessel Syndrome Based on Metabonomics].

Objective To observe the changes of metabolomics in the evolution process of blockade of heart vessel syndrome (BHVS). Methods The formation of BHVS in three stages were sim- ulated by using high-fat forage and ligating the left anterior descending coronary artery. Increased blood lipid was in the early stage of blood stasis syndrome (BSS) group. Atherosclerosis (AS) was formed in the middle stage of BSS group (sub-BSS). Coronary artery was ligated on the basis of AS was the 3rd stage of BSS (BHVS group). There were 8 rats in each group. Totally 24 rats was used as the blank con- trol group and each stage had 8 rats. The changes of metabolite contents were analyzed using principal component analysis (PCA) and partial least squares method (PLS) with gas chromatography-mass spectrometer (GC-MS) among different groups. Results (1) In the 32 kinds of identified metabolites, citric acid was closest associated with the evolution process of BHVS, followed by cholesterol, inositol, ornithine, proline, isoleucine, octadecanoic acid, lactic acid, urea, leucine, linoleic acid, mannose. (2) Metabolic markers in the three stages: octadecanoic acid, lactic acid (positively correlated) , and mannose (negatively correlated) in the early stage of BSS. Ornithine, proline, inositol (positively correla- ted) , and isoleucine (negatively correlated) in the middle stage of BSS (sub-BSS). Leucine, isoleucine, citric acid (positively correlated) , and lactic acid (negatively correlated) in the BHVS stage. Conclusions High fat diet causes disordered in vivo lipid metabolism in pre-stage BSS, and the organism initiates anti- inflammation. Continued high fat diet leads to disordered urea cycle, imbalanced intestinal flora, changed vascular morphology, and liver dysfunction in the sub-BSS stage. Acute myocardial ischemia leads to glucose metabolism disorder in the BHVS stage.

[Relevant Research on ACE Gene Single Nucleotide Polymorphisms and Premature Coronary Heart Disease Patients with Blood Stasis Syndrome].

OBJECTIVE: To explore the relationship between angiotensin converting enzyme (ACE) gene single nucleotide polymorphisms (SNP) and premature coronary heart disease (PCHD) patients with blood stasis syndrome (BSS). METHODS: rs4343, rs4293, and rs4267385 were selected at SNP from ACE gene. Allele and genotype were detected. Frequencies of allele and genotype were compared by using time-of-flight mass spectrometry technique (TOF-MS). RESULTS: Compared with the healthy control group, genotype of rs4293 and rs4267385 in ACE gene were similar, but there was statistical difference in polymorphisms and allele frequencies of rs4343 in the I and II group (P < 0.05, P < 0.01). The frequency of G allele was higher in the 3 groups than in the healthy control group (P < 0.05, P < 0.01). The relative risk analysis showed that the risk for PCHD occurrence in G allele carriers at rs4343 (GG +AG) was 3. 6 times the risk in non-G allele carriers (95% CI: 1.224-10.585, P = 0.02). There was also statistical difference in sex, age, TC, and TG after adjusted Logistic regression analysis (OR = 3.994, 95% CI: 1.230-12.974, P = 0.021). CONCLUSION: The polymorphism at rs4343 (G2350A) might be one of risk factors for PCHD occurrence, but not a predisposing factor for PCHD patients of BSS.

[Study on relationship between the polymorphism of angiotensin converting enzyme gene and blood stasis syndrome in patients with coronary heart disease].

OBJECTIVE: To explore the relationship between the insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE), and blood stasis syndrome (BSS) in patients with coronary heart disease (CHD). METHODS: The ACE gene type in 48 patients of CHD of BSS type, 52 CHD patients of non-BSS type and 54 healthy subjects (control) was determined by PCR assay, also levels of endothelin (ET), angiotensin II (Ag II), and nitric oxide (NO) were determined. RESULTS: Occurrence of DD genotype and allele genotype of ACE gene was higher in patients of BSS than that in patients of non-BSS and control (P < 0.01). ET/NO level was higher in patients of BSS than that in control (P < 0.01). ET and Ag II levels in patients of BSS were significantly higher than those in patients of non-BSS (P < 0.05) and control (P < 0.01). Levels of ET/NO and Ag II in subjects with DD genotype in various groups were higher than those in subjects with Ag II or ID genotype, the highest level occurred in patients of BSS with DD genotype, when compared with the other two groups, the difference in Ag II was significant (P < 0.05 and P < 0.01), when compared with control, the difference in ET/NO was significant (P < 0.01). CONCLUSION: DD genotype of ACE gene may be the susceptible gene of CHD in patients of BSS type.