Background Myocardial infarction (MI), one of the most severe cardiovascular diseases, is influenced by altered macrophage status and metabolic reprogramming (MR), yet the mechanisms of their crosstalk remain unclear. This study used bioinformatics to explore key genes associated with macrophages and MR function in MI.Methods Single-cell and bulk transcriptomics data of MI were obtained from public databases, and MR-related genes (MRGs) were downloaded from literature. Macrophage-associated differentially expressed genes (DEGs1) were identified from the single-cell data. Candidate genes were determined by intersecting MI-related DEGs (DEGs2), DEGs1, and MRGs. Machine learning, gene expression, and receiver operating characteristic (ROC) curve analyses were used to identify key genes. Drug prediction analysis was performed. Single-cell data were further analyzed to explore the underlying biological mechanisms of MI, followed by cell communication and pseudo-temporal analyses. Finally, RT-qPCR was used to validate the mRNA expression of key genes.Results A total of 304 DEGs1, 1,258 DEGs2, and 1,804 MRGs were intersected, identifying 6 candidate genes. The key genes (ABCG1, GNG11, and RPL24) were successfully identified. Pathways co-enriched by key genes included Huntington's disease, olfactory transduction, oxidative phosphorylation, proteasome, and spliceosome. Two drugs targeting ABCG1, APT and vitamin E, were identified. Macrophages displayed significant interactions with B/plasma cells and dendritic cells (DC) in MI samples. The expression of ABCG1 was significantly increased in MI, while GNG11 and RPL24 were decreased.Conclusion ABCG1, GNG11, and RPL24 were identified as key regulators of macrophage function and MR in MI, providing valuable insights for the development of targeted therapies.

PAH is marked by excessive PASMCs and resistance to apoptosis. ERS drives pulmonary vascular remodeling. Betaine from Lycium barbarum L. protects against PAH, is orally available to humans and shows no obvious toxicity for humans and animals at 100, 200, 400 mg/kg. However, the ERS link remains unexplored. This study investigates betaine's PAH protective mechanisms. SD rats received a single subcutaneous injection of notaline to induce PAH and received betaine and sildenafil avenate for 21 d. Betaine significantly improved abnormal changes in echocardiography, hemodynamics, and pathomorphology. Betaine inhibited the proliferation of HPASMCs induced by PDGF-BB. Moreover, betaine suppressed the protein expression of GRP78 and improved the protein expression of p-PERK in rat lungs. It also significantly upregulated PERK and eIF2 alpha phosphorylation in HPASMCs. Upon PERK siRNA knockdown, betaine restores PERK and eIF2 alpha phosphorylation. Betaine activates PERK-eIF2 alpha, mitigates ERS, and targets PERK, as a potential PAH therapy.

Lonicerae Japonicae Flos (LJF, called Jinyinhua in China), comes from the dried flower buds or flowers to be opened of Lonicera japonica Thunb. in the Lonicera family. It has a long history of medicinal use and has a wide range of application prospects. As modern research advances, an increasing number of scientific experiments have demonstrated the anticancer potential of LJF. However, there is a notable absence of systematic reports detailing the anti-tumor effects of LJF. This review integrates the principles of Traditional Chinese Medicine (TCM) with contemporary pharmacological techniques, drawing upon literature from authoritative databases such as PubMed, CNKI, and WanFang to conduct a comprehensive study of LJF. Notably, a total of 507 compounds have been isolated and characterized from the plant to date, which include volatile oils, organic acids, flavonoids, iridoids, triterpenes and triterpenoid saponins. Pharmacological studies have demonstrated that LJF extract, along with components such as chlorogenic acid, luteolin, rutin, luteoloside, hyperoside and isochlorogenic acid, exhibits potential anticancer activities. Consequently, we have conducted a comprehensive review and summary of the mechanisms of action and clinical applications of these components. Furthermore, we have detailed the pharmacokinetics, quality control, and toxicity of LJF, while also discussing its prospective applications in the fields of biomedicine and preventive healthcare. It is hoped that these studies will provide valuable reference for the clinical research, development, and application of LJF.

To investigate the mechanism of action of Banxia-Shengjiang drug pair on the inhibition of gastric cancer (GC) using network pharmacology and bioinformatics techniques. The action targets of the Banxia (Pinellia ternata (Thunb.) Makino) -Shengjiang (Zingiber officinale Roscoe) drug pair obtained from the TCMSP database were intersected with differentially expressed genes (DEGs) and GC-related genes, and the intersected genes were analyzed for pathway enrichment to identify the signaling pathways and core target genes. Subsequently, the core target genes were analyzed for clinical relevance gene mutation analysis, methylation analysis, immune infiltration analysis and immune cell analysis. Finally, by constructing the PPI network of hub genes and corresponding active ingredients, the key active ingredients of the Banxia-Shengjiang drug pair were screened for molecular docking with the hub genes. In this study, a total of 557 target genes of Banxia-Shengjiang pairs, 7754 GC-related genes and 1799 DEGs in GC were screened. Five hub genes were screened, which were PTGS2, MMP9, PPARG, MMP2, and CXCR4. The pathway enrichment analyses showed that the intersecting genes were associated with RAS/MAPK signaling pathway. In addition, the clinical correlation analysis showed that hub genes were differentially expressed in GC and was closely associated with immune infiltration and immunotherapy. The results of single nucleotide variation (SNV) and copy number variation (CNV) indicated that mutations in the hub genes were associated with the survival of gastric cancer patients. Finally, the PPI network and molecular docking results showed that PTGS2 and MMP9 were potentially important targets for the inhibition of GC by Banxia-Shengjiang drug pair, while cavidine was an important active ingredient for the inhibition of GC by Banxia-Shengjiang drug pair. Banxia-Shengjiang drug pair may regulate the immune function and inhibit GC by modulating the expression of core target genes such as RAS/MAPK signaling pathway, PTGS2 and MMP9.

Purpose This study mainly made use of network pharmacology and molecular docking to analyze the therapeutic mechanism of pulmonary arterial hypertension (PAH) by the traditional medicinal food plant Lycium barbarum L. in Ningxia. Methods The related targets and active compounds in PAH and Lycium barbarum L. were analyzed through the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP), GeneCards databases, Online Mendelian Inheritance in Man (OMIM) databases,Cytoscape (3.7.1) software,the STRING database,the Database for Annotation Visualization and Integrated Discovery (DAVID) database. In addition, the main active compounds were molecularly docked with key targets. Results The results showed that 35 active ingredients of Lycium barbarum L. were obtained. The protein-protein interaction (PPI) network includes 140 potential target proteins. Gene Ontology (GO) enrichment analysis yielded 34 entries from three parts: biological processes, cell composition, and molecular function. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis obtained 157 pathways, mainly involving Chemical carcinogenesis receptor activation, Lipid and atherosclerosis, Hepatitis B/C, Chemical carcinogenesis reactive oxygen species, as well as Signaling pathways such as HIF-1, TNF, PI3K-Akt, and MAPK. Molecular docking results showed that the affinity of the key targets to quercetin is less than -5 kcal/mol, and the affinity with betaine is less than 0. Conclusion In conclusion, it was preliminarily predicted that the active compounds of Lycium barbarum L., such as quercetin and betaine, acted on key targets such as AKT1, EGFR, MYC played an intervention role in PAH by regulating multiple signaling pathways, which provided a theoretical basis for the development and application of Lycium barbarum L. and the treatment of PAH.

Background: Coronary artery disease is a prevalent global cardiovascular ailment, with percutaneous coronary intervention (PCI) standing out as a crucial method for relieving symptoms and enhancing the quality of life in patients with coronary heart disease. However, the presence of concurrent chronic total occlusion (CTO) and bifurcation lesions within coronary arteries elevates the complexity and treatment risks, especially when the entry point of the CTO is ambiguous. Objective: This study aims to present an innovative approach for treating CTO complicated with bifurcation lesions, focusing on true cavity pathfinding assisted by a balloon. Methods: Two cases of CTO patients with concomitant bifurcation lesions are described. One case involves CTO of the left anterior descending artery) combined with anterior non-angle trigeminal lesions, while the other entails CTO of the posterior left artery combined with posterior angle trigeminal lesions. True lumen identification using a balloon and subsequent opening of the CTO blood vessel were performed in both cases. Results: In both cases, the true lumen was successfully located with the assistance of a balloon, leading to the successful opening of the CTO blood vessel. This approach not only simplified the procedure but also reduced procedural difficulty and associated risks of complications compared to traditional guide wire operations. Conclusion: The application of true cavity pathfinding assisted by a balloon offers a novel and effective strategy for managing CTO complicated with bifurcation lesions. The method simplifies the procedure, decreases procedural difficulty, and lowers the risk of complications associated with guide wire operations. However, further studies and long-term follow-up data are warranted to validate the reliability and long-term efficacy of this innovative approach.

Objectives:Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease with high mortality. Isorhamnetin (ISO), one of the main natural flavonoids extracted from sea buckthorn, has pharmacological effects such as anti-inflammatory, anti-proliferative and antioxidant. This study aimed to investigate the protective effect of ISO on PAH and its relationship with the phosphorylation of the c-Src tyrosine kinase (p-c-src)/NOX1 signaling pathway. Materials and Methods:Ninety-five rats were randomly divided into five groups. The normal group received only a subcutaneous injection of saline, while the other groups received a subcutaneous injection of monocrotaline(MCT) (60 mg/kg) to establish a PAH model. The treatment group received ISO (50, 100, 150 mg/kg/d) treatment for 21 days, and after 21 days, all rat lung tissues were separated. Results:The results showed that ISO could significantly improve the hemodynamics of MCT-induced PAH rats, such as mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP), and had inhibitory effects on right ventricular hypertrophy in PAH rats, and on pulmonary vascular remodeling in PAH rats. In addition, ISO can reduce the content of 5-hydroxytryptamine (5-HT) in PAH rats, increase the expression of Nrf2 protein in the lung tissue of PAH rats, activate the antioxidant system, enhance the activity of SOD in lung tissue of PAH rats, and inhibit NOX1, 5-HTT, p-c-src and Proliferating Cell Nuclear Antigen(PCNA) protein expression, and decrease MDA content. Conclusion:Our research confirmed the therapeutic effect of ISO on MCT-induced PAH rats, which may be related to regulating the p-c-src/NOX1 signaling pathway.

Over the past few years, there has been a gradual increase in the incidence of cancer, affecting individuals at younger ages. With its refractory nature and substantial fatality rate, cancer presents a notable peril to human existence and wellbeing. Hawthorn, a medicinal food homology plant belonging to the Crataegus genus in the Rosaceae family, holds great value in various applications. Due to its long history of medicinal use, notable effects, and high safety profile, hawthorn has garnered considerable attention and plays a crucial role in cancer treatment. Through the integration of modern network pharmacology technology and traditional Chinese medicine (TCM), a range of anticancer active ingredients in hawthorn have been predicted, identified, and analyzed. Studies have shown that ingredients such as vitexin, isoorientin, ursolic acid, and maslinic acid, along with hawthorn extracts, can effectively modulate cancer-related signaling pathways and manifest anticancer properties via diverse mechanisms. This review employs network pharmacology to excavate the potential anticancer properties of hawthorn. By systematically integrating literature across databases such as PubMed and CNKI, the review explores the bioactive ingredients with anticancer effects, underlying mechanisms and pathways, the synergistic effects of drug combinations, advancements in novel drug delivery systems, and ongoing clinical trials concerning hawthorn’s anticancer properties. Furthermore, the review highlights the preventive health benefits of hawthorn in cancer prevention, offering valuable insights for clinical cancer treatment and the development of TCM with anticancer properties that can be used for both medicinal and edible purposes.

The onset and progression of pulmonary arterial hypertension (PAH), a malignant disease, are associated with environmental and epigenetic factors. Recent advancements in transcriptomics and proteomics technology have provided new insights into PAH and identified novel gene targets involved in the development of the disease. Transcriptomic analysis has led to the discovery of possible novel pathways, such as miR-483 targeting several PAH-related genes and a mechanistic link between the increase in HERV-K mRNA and protein. Proteomic analysis has revealed crucial details, including the loss of SIRT3 activity and the significance of the CLIC4/Arf6 pathway in PAH pathogenesis. Gene profiles and protein interaction networks of PAH have been analyzed, clarifying the roles of differentially expressed genes or proteins in the occurrence and development of PAH. This article discusses these recent advances.

Chronic low-grade inflammation is regarded to an important signature of atherosclerosis (AS). Macrophage (Mψ) and related polarization have been demonstrated to play a crucial role in the occurrence and development of AS inflammation. Butyrate, a bioactive molecule produced by the intestinal flora, has been increasingly demonstrated to exhibit a vital role for regulating the inflammation in chronic metabolic diseases. However, the effectiveness and multiple anti-inflammation mechanisms of butyrate on AS still need to be further understood.ApoE−/−mice fed with high-fat diet as AS model were administered with sodium butyrate (NaB) for 14 weeks of treatment. Our results showed that the atherosclerotic lesion in the AS group was dramatically reduced after NaB intervention. Moreover, deteriorated routine parameters of AS including body weights (BWs), low-density lipoprotein (LDL-C), triglyceride (TG), total cholesterol (TC) were significantly reversed by NaB administration. Abnormal elevated plasma and aorta pro-inflammatory indicators including interleukin (IL)-1β, IL-6, IL-17A, tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS), as well as reduced anti-inflammatory IL-10 in plasma were respectively rectified after NaB administration. Consistently, accumulated Mψ and associated imbalance of polarization in the arota were attenuated with NaB treatment. Importantly, we demonstrated that the suppression of Mψ and associated polarization of NaB was dependent on binding G-protein coupled receptor (GPR) and inhibiting histone deacetylase HDAC3. Moreover, we found that intestinal butyrate-producing bacteria, anti-inflammatory bacteria and intestinal tight junction protein zonula occludens-1 (ZO)-1 may contribute to this effectiveness. Intriguingly, according to transcriptome sequencing of atherosclerotic aorta, 29 elevated and 24 reduced miRNAs were found after NaB treatment, especially miR-7a-5p, suggesting that non-coding RNA may possess a potential role in the protection of NaB against AS. Correlation analysis showed that there were close complicated interactions among gut microbiota, inflammation and differential miRNAs. Collectively, this study revealed that dietary NaB may ameliorate atherosclerotic inflammation by regulating Mψ polarization via GPR43/HDAC-miRNAs axis inApoE−/−mice.

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterised by elevated pulmonary pressure, right ventricular failure (RVF) and ultimately death. Aggressive treatment of RVF is considered an important therapeutic strategy to treat PAH. Previous studies have indicated that betaine may be may a promising therapeutic approach for PAH-induced RVF. Therefore, in this study, betaine solution for injection was prepared and characterised using various techniques. The therapeutic efficacy of three different methods of administration (intragastric, nebulised inhalation and intravenous injection) were comprehensively evaluated in terms of pharmacokinetics, tissue distribution and pharmacodynamics. The pharmacokinetic results demonstrated that betaine injection administered via nebulised inhalation significantly prolonged betaine's half-life and increased its internal circulation time compared to the intragastric and intravenous routes. Biodistribution experiments verified that the betaine formulation accumulated in the lung tissue when administered via inhalation. The results of the pharmacodynamic analysis further confirmed that right ventricular systolic pressure, mean pulmonary artery pressure and right ventricular hypertrophy index increased in the model group and that inhaled betaine suppressed these pathological changes to a level comparable to those observed in the control group. Taken together, these results indicate that betaine administered by inhalation is a promising strategy for the treatment of PAH-induced RVF.

Excessive pulmonary arterial smooth muscle cells (PASMCs) proliferation and anti-apoptosis are vital pathophysiological components of pulmonary arterial remodeling in pulmonary arterial hypertension (PAH). Endoplasmic reticulum stress (ERS) is increasingly recognized as a common pathophysiological reaction to lead to pulmonary vascular remodeling. Betaine is an anti-inflammatory and improve immunity alkaloid, which extracted from Lycium barbarum L. In our previous studies have demonstrated that betaine has protective effects on PAH. Nevertheless, whether the therapeutic effect betaine on PAH is related to ERS remains unclear. Therefore, this study aimed to investigate the effects and mechanisms of betaine on PAH. In vivo, betaine significantly improved abnormal changes in echocardiography, hemodynamics and pathomorphology. The results of CCK-8 showed betaine inhibited proliferation of HPASMCs induced by PDGF-BB of HPASMCs. Furthermore, betaine suppressed protein expression of GRP78, CHOP and Caspase-12 and improved protein expression of p-PERK in rat lungs. Betaine significantly upregulated PERK phosphorylation and eIF2α phosphorylation in HPASMCs. After PERK was intervened with siRNA, betaine could restore the reduction of PERK and eIF2α phosphorylation level caused by PERK siRNA. Betaine played a therapeutic role in treating pulmonary arterial hypertension by enhancing PERK-eIF2α signaling pathway, inhibiting ERS and its target was PERK.

The aim of this study was to investigate the vasodilatory effects of betaine, an alkaloid isolated from Lycium barbarum, on isolated pulmonary artery rings in rats and its possible mechanisms. Pulmonary vessels of normal Sprague-Dawley rats were isolated and pre-contracted using norepinephrine. Then, betaine was cumulatively added in differing concentrations (0.02-0.14 mg/mL), and the tension curve was observed and recorded. Changes in the tension of the pulmonary artery rings with an intact endothelium and a dissected endothelium were recorded. The interactions among betaine and NG-nitro-L-arginine methyl ester, indomethacin, 4-aminopyridine, barium chloride, and glibenclamide were evaluated. The experimental results show that betaine can relax the pulmonary artery rings pre-contracted by norepinephrine. Furthermore, pre-incubation with NG-nitro-L-arginine methyl ester and indomethacin did not inhibit betaine vasodilation, demonstrating that vasodilation by betaine is endothelium-dependent. Additionally, pretreatment of pulmonary artery rings with 4-aminopyridine and glibenclamide had no effect on betaine. However, pretreatment of pulmonary artery rings with barium chloride attenuated the effects of betaine. In conclusion, the vasodilatory effects of betaine on pulmonary artery rings is associated with inward rectifier potassium channels.

Pulmonary vascular remodeling was shown to lead to pulmonary arterial hypertension (PAH), further trigger excessive apoptosis of cardiomyocytes, and ultimately cause right ventricular failure (RVF), which involves the activation of Rho A/ROCK signaling pathway. Betaine has been found efficacious for attenuating PAH through its anti-inflammatory effects in our previous research while its effects on RVF due to PAH remains inconclusive. Thus, we attempted to elucidate the protective effects of betaine on PAH, RVF due to PAH as well as the potential mechanisms. To this end, male Sprague Dawley rats received a single subcutaneous injection of monocrotaline (50 mg/kg) to imitate PAH and RVF, and subsequently oral administration of betaine (100, 200, and 400 mg/kg/day). Betaine treatment improved the hemodynamics and histomorphological parameters and echocardiographic changes. Moreover, betaine also alleviated the pulmonary vascular remodeling and cardiomyocyte apoptosis. The mechanisms study revealed that administration of betaine significantly increased the expression of Rho A, ROCK1, and ROCK2. Furthermore, betaine alleviated the changes of its downstream molecules P53, Bcl-2, Bax, phosphorylated MYPT1 (p-MYPT1), total MYPT1 (t-MYPT1), p27kip1, and Cleaved Caspase-3. According to what we observed, this study indicated that betaine treatment could protect RVF due to PAH, which may be achieved through an altered Rho A/ROCK signaling pathway.

Pulmonary arterial hypertension (PAH) is a malignant disease with high mortality and closely involves the bone morphogenetic protein (BMP) pathway. Mutations in BMPR2 caused proliferation of pulmonary artery smooth muscle cells (PASMCs) leading to PAH. Isorhamnetin, one of the main naturally occurring flavonoids extracted from Hippophae rhamnoides L, shows antiinflammatory and anti‐proliferative properties. Nevertheless, the effects of isorhamnetin on PAH remain unclear. This study aimed to investigate whether isorhamnetin has protective effects against PAH and explore possible mechanisms. An in vivo model of PAH induced by monocrotaline (MCT) was employed, and sildenafil and isorhamnetin were orally administered for 21 consecutive days. An in vitro model induced by TNF‐α was employed, and cell proliferation of HPASMCs was detected. Results indicated that isorhamnetin significantly improved hemodynamic, histopathological, and echocardiographic changes in MCT‐induced PAH in rats. In vitro, isorhamnetin suppressed TNF‐α‐induced HPASMCs proliferation. Furthermore, isorhamnetin improved protein expression of BMPR2 and suppressed protein expression of TNF‐α and IL‐6 in rat lungs. Isorhamnetin improved protein expression of BMPR2 and p‐smad1/5 and mRNA expression of Id1 and Id3 in HPASMCs. Isorhamnetin ameliorated MCT‐induced PAH in rats and inhibited TNF‐α‐induced HPASMCs proliferation by a mechanism likely involving the regulation of the BMP signaling pathway.

Pulmonary arterial hypertension (PAH) is a destructive and rare disorder characterized by a progressive increase in pulmonary artery pressure and vasoconstriction, ultimately leading to right ventricular failure and death. 18β-Glycyrrhetinic acid (18β-GA) is an active ingredient in the commonly used Chinese herbal medicine radix glycyrrhizae, and it possesses antioxidant, anti-inflammatory, anti-tumor, and other pharmacological properties. This study aimed to determine whether 18β-GA has protective effects against monocrotaline (MCT)-induced PAH and whether it is associated with oxidative stress. The PAH of rats was induced by MCT (60 mg/kg) and oral administration of 18β-GA (100, 50, or 25 mg/kg/day), sildenafil (30 mg/kg), or saline for 21 consecutive days. The development of PAH was evaluated by hemodynamic parameters and right ventricular hypertrophy index. Hematoxylin and eosin staining, Masson trichrome staining, and electron microscopy were used to determine the degree of vascular remodeling and proliferation in lung tissue. Moreover, the antioxidant capacity and malondialdehyde levels in the lungs were measured according to the instructions provided by the test kits, and the expression levels of nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox2) and Nox4 were detected through Western blot analysis. Results of our study indicated that 18β-GA treatment significantly improved the hemodynamic and pathomorphological data of the rats, reduced the changes in oxidative stress biomarkers, and inhibited Nox2 and Nox4 expression. Our research indicated that 18β-GA has a protective effect against MCT-induced PAH by inhibiting oxidative stress in rats.

PURPOSE:Excessive proliferation, migration and anti-apoptosis of pulmonary artery smooth muscle cells (PASMCs) are the basis for the development of pulmonary vascular remodeling, and it is the driving force for pulmonary arterial hypertension (PAH). 18β-glycyrrhetinic acid (18β-GA) is the main active substance extracted from Chinese herbal medicine licorice, with outstanding anti-inflammatory, anti-oxidation and anti-proliferative effects. Our team found in previous studies that 18β-GA has protective effects on monocrotaline-induced PAH in rats. However, the anti-angiogenic effect of 18β-GA on PAH remains unclear. Therefore, in order to further investigate whether the beneficial effects of 18β-GA on PAH are related to its antiproliferative effect, we conducted experiments in vivo and in vitro.METHODS AND RESULTS:In vivo, 18β-GA relieved mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricular hypertrophy index, improving pulmonary remodeling. In vitro, 18β-GA significantly inhibited PDGF-BB-induced proliferation and DNA synthesis of HPASMCs, blocking the progression of G0/G1 to S phase of the cell cycle. Furthermore, after treatment with 18β-GA, the expression of Rho A, ROCK1, ROCK2 was decreased and ROCK activity was inhibited in HPASMC. In addition, 18β-GA also attenuated PDGF-induced changes in p27kip1, Bax and Bcl-2.CONCLUSIONS:In summary, these results indicate that 18β-GA regulates the activity of RhoA-ROCK signaling pathway, inhibits the proliferation of HPASMCs, and has potential value in the treatment of PAH.

AIMSCardiovascular disease is the leading cause of death with high morbidity and mortality, and chronic heart failure is the terminal phase of it. This study aimed to investigate the protective effects of the low-dose rosuvastatin on isoproterenol-induced chronic heart failure and to explore the possible related mechanisms.METHODSMale Sprague Dawley rats were given isoproterenol 5 mg/kg once a day for 7 days to establish heart failure model by subcutaneous injection. Simultaneously, low-dose rosuvastatin (5 mg/kg) was orally administrated from day 1 to day 14. Protective effects were evaluated by hemodynamic parameter, histopathological variables, serum asymmetric dimethylarginine (ADMA), cardiac troponin I (cTnI), brain natriuretic peptide (BNP) and myocardial nitric oxide (NO), and the levels of dimethylarginine dimethylaminohydrolase 2 (DDAH2), arginine methyltransferases 1 (PRMT1) and endothelial nitric oxide synthase (eNOS) expression were analyzed.RESULTSTherapeutic rosuvastatin (5 mg/kg) significantly attenuated isoproterenol-induced hypertrophy, remodeling and dysfunction of ventricle, reduced the increased serum content of ADMA, cTnI, and BNP, and elevated myocardial NO in rats (P<.05). Besides, rosuvastatin also significantly inhibited fibrosis of myocardium, normalized the increased PRMT1 and decreased DDAH2 expression.CONCLUSIONSLow-dose rosuvastatin exerted cardioprotective effects on isoproterenol-induced heart failure in rats by modulating DDAH-ADMA-NO pathway, and it may present the new therapeutic value in ameliorating chronic heart failure.

Oxymatrine (OMT) is an active constituent of traditional Chinese herb Sophora japonica Ait which has been shown to exert potent anti-inflammatory,anti-oxidant and anti-fibrosis properties. Our previous studies have demonstrated that OMT has protective effects on isoproterenol-induced heart failure in rats through regulation of DDAH/ADMA metabolism pathway.In this study,we further investigated whether OMT could attenuate isoproterenol-induced heart failure through the regulation of COX-2/PGI2 pathway. Heart failure was induced in Sprague-Dawley rats by 5mg/kg isoproterenol subcutaneous injection for 7days. The rats were maintained on normal diet and randomly divided into five groups: control, isoproterenol, isoproterenol with OMT (50, 100mg/kg), and OMT alone groups (n=12 in each group). Serum brain natruretic peptide (BNP, a heart failure biomarker), histopathological variables, expression of Cytosolic phospholipase A2 (cPLA2), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and Prostacyclin synthase (PGIS) were analysed. Administration of OMT significantly reduced the increased BNP in plasm of isoproterenol-induced rats, attenuated cardiac fibrosis,suppressed overexpression of myocardial COX-1 expression, up-regulated COX-2 and PGIS expression, but had no effects on isoproterenol-induced elevated protein cPLA2. And compared with control group, any indexes in sham rats treated with OMT (100mg/kg) alone were unaltered. These results demonstrated that OMT has cardioprotective effects on isoproterenol-induced heart failure in rats by regulating COX-2/PGI2 pathway.

OBJECTIVE:To investigate the protective effects of oxymatrine on chronic heart failure induced by isoproterenol (ISO) and to observe its effects on ADMA metabolism pathway in ISO-induced chronic heart failure in rats.METHOD:Male Sprague-Dawley rats were given oxymatrine (100,50 mg kg-1) orally for 14 days. Heart failure was induced in rats by subcutaneous injection of isoproterenol (5 mg kg-1 d-1 ) at the 8th day for 1 week. Serum parameters, haemodynamic parameters, Heart weight, and histopathological variables were analysed. Expression of protein levels were measured by Western blot.RESULT:Oxymatrine (100,50 mg kg-1) significantly attenuated serum content of cTn I, improved left ventricle systolic and diastolic function and left ventricular remodeling, reduced the ISO-induced myocardial pathological changes compared with ISO group. In addition, oxymatrine (100,50 mg kg-1) significantly reduced serum level of ADMA (P <0. 01), normalize the reduced dimethylarginine dimethylaminohydrolase 2 (DDAH2) expression (P <0. 01) , but had no effect on the isoproterenol-induced upregulated protein arginine methyltransferases 1 expression.CONCLUSION:Oxymatrine could ameliorate the experimental ventricular remodeling in ISO-induced chronic heart failure in rats and the mechanism involved in reducing serum content of ADMA and increased DDAH2 expression.