[Role of NLRP3 inflammasome in heart failure and traditional Chinese medicine intervention: a review].

Heart failure is characterized by high incidence and mortality rates, and the search for effective treatment strategies for heart failure and the improvement of clinical outcomes have always been important research directions. Imbalanced inflammation has been proven to be one of the critical pathological factors in heart failure, positively correlated with adverse events such as impaired cardiac function and myocardial fibrosis. In recent years, studies have confirmed that the activation of the NOD-like receptor thermal protein domain-associated protein 3(NLRP3) inflammasome plays a common regulatory role in the inflammation imbalance induced by various factors in heart failure. Moreover, certain traditional Chinese medicine(TCM) and active components can significantly inhibit the activation of the NLRP3 inflammasome, thereby improving heart failure. This article first overviewed the basic information about the NLRP3 inflammasome, summarized the regulatory mechanisms of the NLRP3 inflammasome in heart failure induced by various factors, introduced recent research progress on TCM and active components that inhibited the NLRP3 inflammasome to improve heart failure, aiming to provide references for innovative drug research in the field of integrated Chinese and western medicine for the prevention and treatment of heart failure.

[Role of macrophages in heart failure and traditional Chinese medicine intervention].

As the disease with high morbidity and mortality in the world, heart failure affects the development of human society. Due to its complicated pathology and limited treatment options, it is urgent to discover new disease targets and develop new treatment strategies. As innate immune cells accompanied by the evolution of heart failure, macrophages play an important role in cardiac homeostasis and stress. In recent years, the role of macrophages in the heart has attracted more and more attention as a potential target for heart failure intervention, and the research on cardiac macrophages has made important progress. Traditional Chinese medicine(TCM) has significant effects on regulating inflammatory response, treating heart failure, and maintaining homeostasis. In this article, researches on the functions of cardiac macrophages and application of TCM were reviewed from the source and classification of cardiac macrophages and the relationship of macrophages and cardiac inflammation, myocardial fibrosis, cardiac angiogenesis, and cardiac electrical conduction, which provided a basis for further basic research and clinical applications.

[Mechanism of Jiming Powder in ameliorating heart failure with preserved ejection fraction based on metabolomics].

In this study, untargeted metabolomics was conducted using the liquid chromatography-tandem mass spectrometry(LC-MS/MS) technique to analyze the potential biomarkers in the plasma of mice with heart failure with preserved ejection fraction(HFpEF) induced by a high-fat diet(HFD) and nitric oxide synthase inhibitor(Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) and explore the pharmacological effects and mechanism of Jiming Powder in improving HFpEF. Male C57BL/6N mice aged eight weeks were randomly assigned to a control group, a model group, an empagliflozin(10 mg·kg~(-1)·d~(-1)) group, and high-and low-dose Jiming Powder(14.3 and 7.15 g·kg~(-1)·d~(-1)) groups. Mice in the control group were fed on a low-fat diet, and mice in the model group and groups with drug intervention were fed on a high-fat diet. All mice had free access to water, with water in the model group and Jiming Powder groups being supplemented with L-NAME(0.5 g·L~(-1)). Drugs were administered on the first day of modeling, and 15 weeks later, blood pressure and cardiac function of the mice in each group were measured. Heart tissues were collected for hematoxylin-eosin(HE) staining to observe pathological changes and Masson's staining to observe myocardial collagen deposition. Untargeted metabolomics analysis was performed on the plasma collected from mice in each group, and metabolic pathway analysis was conducted using MetaboAnalyst 5.0. The results showed that the blood pressure was significantly lower and the myocardial concentric hypertrophy and left ventricular diastolic dysfunction were significantly improved in both the high-dose and low-dose Jiming Powder groups as compared with those in the model group. HE and Masson staining showed that both high-dose and low-dose Jiming Powder significantly alleviated myocardial fibrosis. In the metabolomics experiment, 23 potential biomarkers were identified and eight strongly correlated metabolic pathways were enriched, including linoleic acid metabolism, histidine metabolism, alpha-linolenic acid metabolism, glycerophospholipid metabolism, purine metabolism, porphyrin and chlorophyll metabolism, arachidonic acid metabolism, and pyrimidine metabolism. The study confirmed the pharmacological effects of Jiming Powder in lowering blood pressure and ameliorating HFpEF and revealed the mechanism of Jiming Powder using the metabolomics technique, providing experimental evidence for the clinical application of Jiming Powder in treating HFpEF and a new perspective for advancing and developing TCM therapy for HFpEF.

[Effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction].

Jiming Powder is a traditional ancient prescription with good therapeutic effect in the treatment of heart failure, but its mechanism lacks further exploration. In this study, a mouse model of coronary artery ligation was used to evaluate the effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction. The study constructed a mouse model of heart failure after myocardial infarction using the method of left anterior descending coronary artery ligation. The efficacy of Jiming Powder was evaluated from multiple angles, including ultrasound imaging, hematoxylin-eosin(HE) staining, Masson staining, Sirius Red staining, and serum myocardial enzyme spectrum detection. Western blot analysis was performed to detect key proteins involved in ventricular remodeling, including transforming growth factor-ß1(TGF-ß1), α-smooth muscle actin(α-SMA), wingless-type MMTV integration site family member 3a(Wnt3a), ß-catenin, matrix metallopeptidase 2(MMP2), matrix metallopeptidase 3(MMP3), TIMP metallopeptidase inhibitor 1(TIMP1), and TIMP metallopeptidase inhibitor 2(TIMP2). The results showed that compared with the model group, the high and low-dose Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVID;s) and diastole(LVID;d), increased the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improved cardiac function in mice after myocardial infarction, and effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactic dehydrogenase(LDH), thus protecting ischemic myocardium. HE staining showed that Jiming Powder could attenuate myocardial inflammatory cell infiltration after myocardial infarction. Masson and Sirius Red staining demonstrated that Jiming Powder effectively inhibited myocardial fibrosis, reduced the collagen Ⅰ/Ⅲ ratio in myocardial tissues, and improved collagen remodeling after myocardial infarction. Western blot results showed that Jiming Powder reduced the expression of TGF-ß1, α-SMA, Wnt3a, and ß-catenin, decreased the levels of MMP2, MMP3, and TIMP2, and increased the level of TIMP1, suggesting its role in inhibiting cardiac fibroblast transformation, reducing extracellular matrix metabolism in myocardial cells, and lowering collagen Ⅰ and α-SMA content, thus exerting an anti-myocardial fibrosis effect after myocardial infarction. This study revealed the role of Jiming Powder in improving ventricular remodeling and treating myocardial infarction, laying the foundation for further research on the pharmacological effect of Jiming Powder.

[Detoxification of cardiotoxic traditional Chinese medicine and traditional Chinese medicine for prevention of cardiotoxicity: a review].

Cardiotoxicity is smong the main safety problems of drugs in clinical application. In recent years, traditional Chinese medicine has been gradually emphasized and studies on the evaluation of cardiac safety and prevention of cardiotoxicity of Chinese medicine have been on the rise, particularly the cardiotoxic Chinese medicine or the Chinese medicine components targeting cardiotoxicity. As for the research methods for cardiac safety evaluation of Chinese medicine, this review introduces the related clinical indexes and cell and animal models. As to the improvement of heart safety, this study reviews the material basis and mechanism of cardiotoxic Chinese medicines as well as the alleviation of cardiotoxicity by controlling the content of toxic compounds and changing dosage form, processing method, and compatibility of Chinese medicine. In addition, the effective components and mechanisms of prescriptions and active compounds in Chinese medicine for preventing and treating cardiotoxicity induced by chemotherapeutic drugs in recent years were summarized. This review is expected to serve as a reference for cardiac safety evaluation and clinical rational application of Chinese medicine.

[Common anti-inflammatory effects of heat-clearing and toxin-removing Chinese medicines on diverse cardiovascular diseases].

Cardiovascular diseases seriously affect human health and their prevalence continues to increase with the aging of the population. The integrated therapy of traditional Chinese medicine(TCM) and western medicine for cardiovascular diseases has achieved certain results, but it is still faced with new challenges. Studies have shown that inflammation plays an important role in the development of cardiovascular diseases and some of these mechanisms have common features. For example, in cardiovascular diseases, C-C motif chemokine receptor 2(CCR2)-expressing macrophages increase and promote inflammation, and excessive activation of NOD-like receptor protein 3(NLRP3) inflammasome leads to the elevation of inflammatory factors. There is also new understanding of the pathogenesis and treatment of cardiovascular diseases in TCM. The heat-toxicity theory in cardiovascular diseases and the therapeutic principle of clearing heat and removing toxin have attracted attention. The clinical and pharmacological studies on the treatment of cardiovascular diseases such as Huanglian Jiedu Decoction and Simiao Yong'an Decoction are also gradually increasing. The present study analyzed the common features of the inflammatory response mechanisms in diverse cardiovascular diseases and discussed the significance of the prevention and treatment of diverse cardiovascular diseases by the treatment method of clearing heat and removing toxin to regulate inflammation, which is expected to provide new ideas and references for clinical treatment and drug research on cardiovascular diseases with the same treatment method for different diseases.

[Construction of "2R network pharmacology" research method for effective components of traditional Chinese medicine based on "prediction of dominant components-screening of potential targets"].

Chinese traditional medicine compound is the main form of Chinese medicine clinical application. The elucidation of the effective components of traditional Chinese medicine is one of the key scientific issues to promote the modernization of traditional Chinese medicine. At present, there are many research ideas on the effective components of traditional Chinese medicine compounds. By analyzing the current status and existing problems of existing research ideas, the author proposes a "double reduction network pharmacology"(2 R network pharmacology) research method based on "prediction of dominant components-potential target selection". Chemical components with good properties were selected by ADMET property prediction technology, and compared with the blood components and target organ components to determine the dominant components with potential therapeutic effect, that is "reducing constituents"; the potential core regulatory pathway of traditional Chinese medicine compound was enriched by RNA-Seq technology combined with network database, and then the target of traditional Chinese medicine compound was mined based on the signal pathway, that is "reducing targets". To improve the efficiency and accuracy of effective component screening, the network relationship of "component target" was established by the related technology of network pharmacology. The purpose of this study is to provide practical research ideas and methods for clarifying the effective components of traditional Chinese medicine, revealing the law of compatibility of traditional Chinese medicine and clarifying the target of drug action.

Chlorogenic acid: A potent molecule that protects cardiomyocytes from TNF-α-induced injury via inhibiting NF-κB and JNK signals.

The traditional Chinese herb Lonicerae Japonicae Flos has shown significant clinical benefits in the treatment of heart failure, but the mechanism remains unclear. As the main active ingredient found in the plasma after oral administration of Lonicerae Japonicae Flos, chlorogenic acid (CGA) has been reported to possess anti-inflammatory, anti-oxidant and anti-apoptosis function. We firstly confirmed the cardioprotective effects of CGA in transverse aortic constriction (TAC)-induced heart failure mouse model, through mitigating the TNF-α-induced toxicity. We further used TNF-α-induced cardiac injury in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to elucidate the underlying mechanisms. CGA pre-treatment could reverse TNF-α-induced cellular injuries, including improved cell viability, increased mitochondrial membrane potential and inhibited cardiomyocytes apoptosis. We then examined the NF-κB/p65 and major mitogen-activated protein kinases (MAPKs) signalling pathways involved in TNF-α-induced apoptosis of hiPSC-CMs. Importantly, CGA can directly inhibit NF-κB signal by suppressing the phosphorylation of NF-κB/p65. As for the MAPKs, CGA suppressed the activity of only c-Jun N-terminal kinase (JNK), but enhanced extracellular signal-regulated kinase1/2 (ERK1/2) and had no effect on p38. In summary, our study revealed that CGA has profound cardioprotective effects through inhibiting the activation of NF-κB and JNK pathway, providing a novel therapeutic alternative for prevention and treatment of heart failure.

iTRAQ-based quantitative proteomic analysis provides insight for molecular mechanism of neuroticism.

BACKGROUND: Neuroticism is a core personality trait and a major risk factor for several mental and physical diseases, particularly in females, who score higher on neuroticism than men, on average. However, a better understanding of the expression profiles of proteins in the circulating blood of different neurotic female populations may help elucidate the intrinsic mechanism of neurotic personality and aid prevention strategies on mental and physical diseases associated with neuroticism. METHODS: In our study, female subjects were screened for inclusion by the Eysenck Personality Questionnaire (EPQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) scales and routine physical examination. Subjects who passed the examination and volunteered to participate were grouped by neuroticism using EPQ scores (0 and 1 = low neuroticism group; > 5 = high neuroticism group). Proteins in serum samples of the two neuroticism groups were identified using isobaric tags for relative and absolute quantification (iTRAQ) technology. RESULTS: A total of 410 proteins exhibited significant differences between high and low neuroticism, 236 proteins were significantly upregulated and 174 proteins were significantly downregulated. Combine the results of GO and KEGG enrichment analysis of differences proteins between high and low neuroticism with the PPI network, it could be observed that the Alpha-synuclein (SNCA), ATP7A protein (ATP7A), Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (GNG2), cyclin-dependent kinase 6 (CDK6), myeloperoxidase (MPO), azurocidin (AZU1), Histone H2B type 1-H (HIST1H2BH), Integrin alpha-M (ITGAM) and Matrix metalloproteinase-9 (MMP9) might participate in the intrinsic mechanism of neuroticism by regulating response to catecholamine stimulus, catecholamine metabolic process, limbic system development and transcriptional misregulation in cancer pathway. CONCLUSIONS: Our study revealed the characteristics of the neurotic personality proteome, which might be intrinsic mechanism of the neurotic population.

[Anti-inflammatory mechanism of heat-clearing and detoxifying Chinese herbs].

Heat-clearing and detoxifying Chinese herbs (HDCHs) are mainly used to treat carbuncle, sore throat, erysipelas, gills, dysentery and other diseases induced by heat-toxicity. Inflammation is a defensive response to damaging factors in living organism with vascular system. In recent years, a large amount of experimental and clinical studies showed that HDCHs had good therapeutic effect on inflammation. This review analyzed the anti-inflammatory mechanism of 11 HDCHs by retrieving literature in past 5 years, including Lonicerae Japonicae Flos (Jinyinhua), Lonicerae Flos (Jinyinhua), Lonicerae Japonicae Caulis (Rendongteng), Forsythiae Fructus (Lianqiao), Rhizoma Coptidis（Huanglian）, Gardeniae Fructus (Zhizi), Andrographis Herba (Chuanxinlian), Taraxaci Herba (Pugongying), Scrophulariae Radix (Xuanshen), Pulsatillae Radix (Baitouweng), and Agrimoniae Herba (Xianhecao). The data showed that the regulatory effect of HDCHs on inflammation may be involved mainly in the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK) or janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, with similarity of action links among these three. Based upon the analysis of literature, we proposed some promising directions in this research field, providing a reliable theoretical basis for both experimental researches and clinical practices of HDCHs.

[Overview of research projects funding in traditional Chinese medicine oncology field supported by National Natural Science Foundation of China].

In this paper, the funding situation of traditional Chinese medicine oncology research projects supported by National Natural Science Fund from 1986-2016 was reviewed. The characteristics of funded projects were summarized from funding amount, funding expenses, funding category, and the main research contents of projects, etc. At the same time, the main problems in the projects were analyzed in this paper, in order to provide reference for the relevant fund applicants.

[Analysis of projects funded by NSFC in field of Chinese material medica resource in recent three years].

The paper reviewed the sponsorship and final reports of projects focus on Science of Chinese materia medica resource in Medical Science Department, National Natural Science Foundation of China. The applicant and supportive organizations were analyzed. The progress and results of some projects were summarized by research fields including formation mechanism of Dao-di herbs, research of plant taxonomy, breeding and cultivation of medical plants, ecological and environmental adaptability of Chinese materia medica resource, quality assessment of Chinese materia medica resource, and biosynthesis and regulation of active compounds. In addition, the potential problems and the most and least focused areas in the application were summarized for reference.

Role of SIRT1 in Streptococcus pneumoniae-induced human ß-defensin-2 and interleukin-8 expression in A549 cell.

Streptococcus pneumoniae is an important pathogen of pneumonia in human. Human alveolar epithelium acts as an effective barrier and is an active participant in host defense against invasion of bacterial by production of various mediators. Sirtuin 1 (SIRT1), the prototypic class III histone deacetylase, is involved in the molecular control of lifespans and immune responses. This study aimed at examining the role of SIRT1 in mediating S. pneumoniae-induced human ß-defensin-2 (hBD2) and interleukin-8(IL-8) expression in the alveolar epithelial cell line A549 and the underlying mechanisms involved. A549 cells were infected with S. pneumoniae for indicated times. Exposure of A549 cells to S. pneumoniae increased the expressions of SIRT1 protein, hBD2 and IL-8 mRNA, and protein. The SIRT1 activator resveratrol enhanced S. pneumoniae-induced gene expression of hBD2 but decreased IL-8 mRNA levels. Blockade of SIRT1 activity by the SIRT1 inhibitors nicotinamide reduced S. pneumoniae-induced hBD2 mRNA expression but increased its stimulatory effects on IL-8 mRNA. S. pneumoniae-induced activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). SIRT1 expression was attenuated by selective inhibitors of ERK and p38 MAPK. The hBD2 mRNA production was decreased by pretreatment with p38 MAPK inhibitor but not with ERK inhibitor, whereas the IL-8 mRNA expression was controlled by phosphorylation of ERK. These results suggest that SIRT1 mediates the induction of hBD2 and IL-8 gene expression levels in A549 cell by S. pneumoniae. SIRT1 may play a key role in host immune and defense response in A549.

[Effects of a compound Chinese herbal medicine Yixin Jiedu formula on haemodynamic in rats with heart failure of qi-deficiency and blood stasis syndrome].

OBJECTIVE: To explore the effects of Yixin Jiedu Formula (YXJDF), a compound Chinese herbal medicine, on hemodynamic and B-type natriuretic (BNP) in a rat model of heart failure with qi deficiency and blood stasis syndrome. Moreover, its therapeutic effects in improving the symptoms were also studied. METHODS: The model of heart failure was established by ligation of left coronary artery in rats. Rats were randomly divided into sham-operated group, model group, YXJDF group and positive control (sodium fosinopril tablet) group. On the second day after the operation, rats in different groups received different treatments. Rats in the YXJDF group were treated with YXJDF (9.33g/kg); rats in the positive control group received solution of sodium fosinopril tablet (1.2mg/kg) and rats in the model and the control groups were given an equal volume of saline, respectively. Drugs were delivered by intragastric administration for 28d. Symptoms such as respiratory rate and red-green-blue value of color of the plantar skin were also collected. Then hemodynamic indexes were evaluated and the levels of plasma BNP were examined by enzyme-linked immunosorbent assay (ELISA) in all groups. RESULTS: After 28d, rats in the YXJDF group and the positive control group were more active than rats in the model group. Both YXJDF and sodium fosinopril tablet significantly improved the purple degree of the plantar skin and the respiratory rate. Compared with rats in the sham-operated group, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) of the model group decreased significantly (P<0.05); rats in the YXJDF group and the positive control group showed significant improvement on SBP, DBP and MAP (P<0.05). In ventricular hemodynamic, left ventricular systolic pressure (LVSP), maximal rate of left ventricular systolic pressure (LV+dP/dt(max)) and maximal rate of left ventricular diastolic blood pressure (LV-dP/dt(max)) of the model group were significantly down-regulated when compared with the sham-operated group (P<0.05); YXJDF and sodium fosinopril tablet increased the LVSP, LV+dP/dt(max) and LV-dP/dt(max) (P<0.05), and thus improved ventricular hemodynamic in rats with heart failure. ELISA results showed that plasma BNP level of the model group was higher than that of the sham-operated group (P<0.05); YXJDF and sodium fosinopril tablet down-regulated the plasma BNP level significantly (P<0.05) compared with the model group. CONCLUSION: YXJDF can strengthen left ventricular contractile force, increase LVSP, LV+dP/dt(max) and LV-dP/dtmax, SBP and SDP, and MAP, and improve hemodynamic indicators in rats with heart failure after myocardial infarction. YXJDF can also relieve the symptoms of qi deficiency and blood stasis syndrome.

[Analysis of plasma metabonomics of mini-swines with qi deficiency and blood stasis syndrome due to chronic myocardial ischemia].

OBJECTIVE: To study the changes of plasma metabolites of mini-swines with qi deficiency and blood stasis syndrome due to chronic myocardial ischemia and to explore the relationship between plasma metabonomics and qi deficiency and blood stasis syndrome. METHODS: Twenty-two mini-swines were used in this study and were divided into sham-operation group (n=10) and model group (n=12). Ameroid constrictors were placed around the left anterior descending coronary artery of mini-swines in model group to induce chronic myocardial ischemia. Twelve weeks after Ameroid placement, physical signs, coronary angiography and echocardiography were used to evaluate qi deficiency and blood stasis syndrome; gas chromatography-mass spectrometry (GC-MS) and data mining method were used to analyze plasma metabolites of the mini-swines. RESULTS: Twelve weeks after operation, mini-swines in model group were confirmed with qi deficiency and blood stasis syndrome. Principal component analysis (PCA) found that plasma GC-MS spectra of the two groups were significantly different. Compared with sham-operation group, endogenous metabolites in plasma were changed in model group. The levels of lipid metabolites such as glycerol, acetic acid and tricosadiynoic acid, myo-inositol, as well as amino acid metabolite proline were raised, while concentrations of glucose (eg. d-glucose, and a-D-glucoside), amino acid (eg. alanine, phenylalanine, and urea) and lipid metabolites (eg. hexadecanoic acid, propionic acid, butanoic acid, and octadecanoic acid) were declined. CONCLUSION: Significant differences in metabolic spectrum exist in mini-swines with qi deficiency and blood stasis syndrome due to chronic myocardial ischemia and normal mini-swines. Disorders in glucose, amino acid and lipid metabolism result in a deterioration of coronary artery disease; citric acid, glucose, octadecanoic acid, hexadecanoic acid, glycerol and acetic acid are contributory to separation of the healthy from qi deficiency and blood stasis syndrome. These metabolites pattern may be used in clinical diagnosis and treatment of coronary artery disease, and also can provide a new approach to objective research in traditional Chinese medicine syndrome.

Deciphering the effective combinatorial components from Si-Miao-Yong-An decoction regarding the intervention on myocardial hypertrophy.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Miao-Yong-An decoction (SMYAD), a classical traditional Chinese medicine (TCM) formula, has been used to treat various cardiovascular diseases in clinics. AIM OF THE STUDY: The aim of this study is to investigate the effective combinatorial components from SMYAD and its mechanism regarding the intervention on myocardial hypertrophy. MATERIALS AND METHODS: SMYAD constituents absorbed in rat plasma and heart were identified using UHPLC Q-Exactive-Orbitrap MS/MS. The identified constituents in SMYAD were further analyzed using ADMET (absorption, distribution, metabolism, excretion and toxicity) prediction and molecular docking. The effective constituents were identified using isoproterenol (ISO)-induced H9c2 cardiomyocyte hypertrophy, and neochlorogenic acid (NCA), chlorogenic acid (CA), cryptochlorogenic acid (CCA), isochlorogenic acid C (ICAC), angoroside C (AGDC), isochlorogenic acid A (ICAA), sweroside (SRD), and harpagide (HPD) in SMYAD extract were quantified by HPLC for compatibility. Finally, anti-hypertrophic activities of candidate effective combinatorial components, which were prepared according to the determined molar concentration ratio of effective constituents using reference substance solution, were analyzed using immunofluorescence staining and Quantitative real-time PCR. The expression levels of PI3Kα, p-ERK, p-Akt, Akt, p-mTOR, mTOR and HIF-1α were measured using Western blot. RESULTS: 32 prototypes of SMYAD were identified from plasma and heart tissue of rat. Combining with ADMET prediction, 31 dominant constituents were focused. Based on HIF-1 pathway identified in preliminary result, 17 targets were focused, which were used to dock with 31 constituents. 27 constituents were therefore hit as the potential effective constituents of SMYAD in inhibiting myocardial hypertrophy. Bioactivity evaluation showed that NCA, CA, CCA, ICAC, AGDC, ICAA, SRD, and HPD significantly inhibited the increase of H9c2 cell surface area induced by ISO. Except for ICAA and AGDC, the remaining 6 effective constituents, showing a certain inhibitory effect on ISO-induced ANP mRNA overexpression at high and low concentrations, participated in compatibility based on the molar concentration ratio determined by HPLC. Effective combinatorial components composed of the 6 effective constituents (effective combinatorial components ABC) showed significant inhibitory effect on the increase of cell surface area, and the overexpression of ANP and ß-MHC mRNA in H9c2 cells induced by ISO. Moreover, effective combinatorial components ABC significantly inhibited the protein overexpressions of p-Akt, p-mTOR and HIF-1α. Based on the results, we put forward the strategy of "Focusing constituents" and "Focusing targets" for the effective constituents research of TCM formula. CONCLUSION: Effective combinatorial components ABC composed of NCA, CA, CCA, ICAC, SRD and HPD from SMYAD inhibited ISO-induced cardiomyocyte hypertrophy and down-regulated expression of ANP and ß-MHC mRNA through the inactivation of Akt/mTOR/HIF-1α pathway.

[Diagnosis and treatment rule of traditional Chinese medicine for syndrome factors of chronic congestive heart failure: a study based on Shannon entropy method].

OBJECTIVE: The primary aim of this research is to systematically sort out and analyze available clinical documents for chronic congestive heart failure in traditional Chinese medicine (TCM) and integrated traditional Chinese and Western medicine, and to explore the diagnosis and treatment rule of TCM syndrome factors with data mining method. METHODS: Based on the China National Knowledge Internet (CNKI) and Chinese Biomedical Literature Database (CBM), using "chronic heart failure" or "chronic congestive heart failure" or "chronic cardiac insufficiency" and "traditional Chinese medicine" or "syndrome" or "integrated traditional Chinese and Western medicine" as keywords for literature selection, we used Shannon entropy nonlinear complex system method for the feature extraction after data preprocessing. RESULTS: The statistics showed that yang deficiency, qi deficiency, blood stasis, water retention, yin deficiency, and turbid phlegm were principal TCM syndrome factors; herbs of qi-tonifying, blood-activating, water-draining, phlegm-dispelling, exterior-releasing, interior-warming were main drugs for clinical application. The symptoms and Chinese herbs which intimately connect with TCM syndrome factors were extracted, while their diagnostic contribution degrees were quantified by correlation coefficient. The symptoms which had high scores were general syndromes while the symptoms which had low scores were specific manifestations of a certain patient. Common Chinese herbs corresponding to each syndrome factor were picked out, indirectly reflecting their frequencies in clinical application. CONCLUSION: Based on data mining of the relationship among the four diagnostic methods of TCM, syndrome factors and herbs, this study provided references for differentiation of TCM syndrome and selection of Chinese medicine according to clinical syndrome factors.

[Duplication of an animal model of myocardial ischemia with blood stasis syndrome in mini-swines].

OBJECTIVE: To establish an animal model of myocardial ischemia with blood stasis syndrome in mini-swines. METHODS: An animal model of myocardial ischemia was established in mini-swines by oppressing the coronary artery through the expansion of inner layer of Ameroid constrictor and the Ameroid constrictor was implanted into the distal end of the initial part of the first branch of interventricular septum of ramus descendens anterior arteriae coronariae sinistrae. Dynamic observation of behavior changes, general health status and changes of hemorheological parameters in the mini-swines were made after operation. RESULTS: The coronary angiography showed that the stenosis rate in ischemic group was more than 75% four weeks after operation. Compared with before operation and sham-operated group, there were great changes of behavior, general health status, tongue color and hemorheological parameters in ischemic group (P<0.05). CONCLUSION: The animal model of myocardial ischemia with blood stasis syndrome in mini-swines was established successfully 4 weeks after operation. The pathological process in the animal model is similar to that in the patients with chronic myocardial ischemia. So this model can be adopted in the research of myocardial ischemia with blood stasis syndrome.

Induction of matrix metalloproteinase, cytokines and chemokines in rat cortical astrocytes exposed to plasminogen activators.

Plasminogen activators are used in thrombolytic stroke therapy. However, it is increasingly recognized that they have other actions besides fibrinolysis. In this study, we assess potential pro-inflammatory effects of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) in rat cortical astrocytes. Both uPA and tPA induced rapid dose-dependent upregulation in MMP-2 and MMP-9, as demonstrated by zymography of conditioned media. In addition, a multiplex ELISA array demonstrated that patterned responses in chemokines and cytokines were also evoked. Exposure to tPA induced elevations in secreted MIP-2, MCP-1 and GRO/KC. Exposure to uPA induced elevations in secreted IFN-gamma, TNF-alpha, GMCSF, MIP-1alpha, MIP-2, MIP-3alpha, MCP-1, RANTES and fractalkine. These data suggest that plasminogen activators may trigger selected pro-inflammatory responses at the neurovascular interface. Whether these effects influence thrombolytic stroke therapy warrants further investigation.

The protective effect of the active components of ERPC on diabetic peripheral neuropathy in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Euonymus alatus, Radix trichosanthis, Panax notoginseng and Coptis chinensis are popular plants used in traditional Chinese medicine to treat diabetes. AIM OF THE STUDY: The aim of the study is to investigate the therapeutic effect of the active components of Euonymus alatus, Radix trichosanthis, Panax notoginseng and Coptis chinensis (cERPC) on diabetic peripheral neuropathy in the rats and explore the underlying mechanism involved. METHODS: After diabetes was induced in rats for 20 weeks, cERPC or water was administered for 12 weeks. After a hot plate test, motor nerve conduction velocity and sciatic nerve blood flow were determined; the sciatic nerves were isolated for toluidine blue staining; and the fibre area, fibre diameter, axon area, axon diameter and myelin thickness were evaluated. The levels of the myelin basic protein, myelin protein zero, Oct6 and Krox20 were measured by western blot or immunofluorescence. RESULTS: cERPC was efficient in reducing the response latency, increasing motor nerve conduction velocity, enhancing sciatic nerve blood flow and ameliorating the pathological changes in diabetic rats. cERPC also had a role in increasing the levels of myelin basic protein and myelin protein zero and improving the expression of Oct6 and Krox20 in sciatic nerves of diabetic rats. CONCLUSIONS: cERPC ameliorates diabetic peripheral neuropathy by attenuating electrophysiological, circulatory and morphological alterations, which is mediated by the Oct6-Krox20 pathway.