Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

OBJECTIVETo evaluate the protective effect of quercetin against lipopolysaccharide (LPS)-induced cardiac injury in mice.

METHODSC57BL/6J mice were randomized into 4 groups to receive intraperitoneal injection of saline (negative control) or LPS (20 mg/kg), or fed with quercetin (100 mg/kg for 7 days) with or without subsequent LPS injection (quercetin+LPS group and quercetin control group, respectively). Six hour after LPS injection, the mice were tested for cardiac function with an echocardiograph, and the protein expressions of Bax, Bcl-2, iNOS, and eNOS in the myocardium were evaluated with Western blotting; serum NO concentration was also measured. The survival of the mice within 5 days after LPS injection was recorded to draw the survival curve.

RESULTSQuercetin pretreatment significantly improved the cardiac function of LPS-challenged mice (P<0.05), and attenuated LPS-induced increment in myocardial iNOS expression and decrement in eNOS level. LPS significantly increased the myocardial Bax expression and slightly decreased Bcl-2 expression; quercetin pretreatment decreased Bax expression to the control level and significantly lowered Bax/Bcl-2 ratio as compared with the LPS group. Serum NO level was significantly increased by nearly 2.5 folds in LPS-challenged mice, but was markedly decreased with quercetin pretreatment (P<0.05). The 5-day survival rate of LPS-treated mice was 10%, which was increased to 45% in quercetin- pretreated mice (P<0.05).

CONCLUSIONQuercetin can alleviate LPS-induced cardiac dysfunctions in mice to increase their survival rate following LPS challenge.

Animals ; Cardiotonic Agents ; pharmacology ; Heart ; drug effects ; Lipopolysaccharides ; adverse effects ; Mice ; Mice, Inbred C57BL ; Myocardium ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Quercetin ; pharmacology

Anthracyclines ; administration & dosage ; adverse effects ; Antineoplastic Agents ; administration & dosage ; adverse effects ; Biomarkers ; blood ; Cardiomyopathies ; chemically induced ; diagnosis ; prevention & control ; Cardiotonic Agents ; therapeutic use ; Child ; Child, Preschool ; Echocardiography ; Heart ; drug effects ; Heart Diseases ; chemically induced ; diagnosis ; prevention & control ; Humans ; Risk Factors ; Survival Analysis ; Troponin I ; analysis

OBJECTIVETo investigate the effects of Chinese herbs for supplementing qi, nourishing yin and activating blood circulation on heart function of patients with acute coronary syndrome (ACS) after successful percutaneous coronary intervention (PCI).

METHODSOne hundred patients with ACS after successful PCI were randomly assigned to a Western medicine (WM) treatment group (WMG) and a combined treatment group (CMG) treated by Chinese herbs for supplementing qi, nourishing yin and activating blood circulation, besides Western medicine treatment, with 50 cases in each group. Both treatment courses were 6 months. The followup was scheduled at baseline, 6 months and 1 year after PCI, and New York Heart Association (NYHA) functional class, Chinese medicine (CM) symptom scores, blood stasis syndrome scores, and major adverse cardiovascular events (MACE) were observed, serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and hyper-sensitivity C-reactive protein (Hs-CRP) were measured, an echocardiogram was conducted to examine left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), inter-ventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), and ventricular wall motion index (VWMI).

RESULTSCompared with the baseline, LVEF significantly increased (P<0.01), and CM symptom scores, blood stasis syndrome scores, VWMI, LVEDV, LVESV, NT-proBNP, and Hs-CRP all decreased (P<0.01) in both groups at 6 months and at 1 year after PCI. There were no significant differences in all the above parameters at 1 year vs those at 6 months after PCI (P>0.05). VWMI, LVEDV, LVESV, NT-proBNP, Hs-CRP, LVEF, and CM symptom and blood stasis syndrome scores were all improved obviously in CMG than those in WMG (P<0.05 or P<0.01) at 6 months and at 1 year after PCI. There were no significant differences in NYHA functional class between CMG and WMG at different follow-up timepoints; it was notable that value was 0.054 when comparing the cases of NYHA functional class between the two groups at 1-year follow-up. During the 1-year follow-up, 3 MACE and 11 MACE occurred in CMG and WMG, respectively; the MACE rate in CMG was lower than that in WMG (6% vs 22%, P<0.05).

CONCLUSIONChinese herbs for supplementing qi, nourishing yin and activating blood circulation could improve heart function, reduce the CM symptom scores and blood stasis syndrome scores, and decrease the incidence of MACE in patients with ACS after successful PCI.

Acute Coronary Syndrome ; blood ; drug therapy ; physiopathology ; surgery ; C-Reactive Protein ; metabolism ; Cardiotonic Agents ; adverse effects ; pharmacology ; therapeutic use ; China ; epidemiology ; Coronary Circulation ; drug effects ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Female ; Heart Function Tests ; drug effects ; Humans ; Incidence ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; New York ; Peptide Fragments ; blood ; Percutaneous Coronary Intervention ; adverse effects ; Postoperative Complications ; epidemiology ; etiology ; Qi ; Societies, Medical ; Syndrome ; Ultrasonography ; Yin-Yang

Aspirin ; therapeutic use ; Bisoprolol ; therapeutic use ; Cardiomyopathies ; chemically induced ; etiology ; Cardiotonic Agents ; adverse effects ; Chest Pain ; diagnostic imaging ; Dobutamine ; adverse effects ; Echocardiography, Stress ; adverse effects ; Enalapril ; therapeutic use ; Humans ; Male ; Middle Aged ; Simvastatin ; therapeutic use

Periventricular-intraventricular hemorrhage (PV-IVH) is a major cause of neurological disabilities in preterm newborns. This study aimed to determine the perinatal factors associated with PV-IVH. We conducted a retrospective case-control study from preterm infants born at < or =34 weeks of gestation and admitted to Neonatal Intensive Care Units of Seoul National University Children's Hospital and Seoul National University Bundang Hospital between June 2003 and December 2007. Neonates with no cranial sonographic data or infants transferred from other centers after three days of age were excluded. Of 1,044 eligible subjects, 59 infants with PV-IVH grade 2, 3, and 4 were allocated to the case group. The control group consisted of 118 infants without PV-IVH who were matched for gestational age and birth weight to each case of PV-IVH. At the multivariate logistic regression model, metabolic acidosis (odds ratio [OR]: 6.94; 95% confidence interval [CI]: 1.12-43.23) and use of inotropes (OR: 3.70; 95% CI: 1.16-11.84) were associated with an increased risk of PV-IVH. Maternal use of antenatal corticosteroids decreases the risk of PV-IVH (OR: 0.36; 95% CI: 0.14-0.92).
Acidosis/complications ; Adult ; Birth Weight ; Cardiotonic Agents/adverse effects ; Case-Control Studies ; Cerebral Hemorrhage/*etiology/pathology ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/*etiology/pathology ; Male ; Odds Ratio ; Pregnancy ; Retrospective Studies ; Risk Factors

Traditional non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 selective inhibitors are among the most widely used drugs. However, their significant side effects in gastrointestinal and cardiovascular systems limited the use of these drugs. Recently, research and development of NO-donating NSAIDs (NO-NSAIDs) have become one of the most important strategies to reduce these side effects. NO-NSAIDs may exert a broad range of positive effects in terms of NO-mediated gastrointestinal and cardiovascular safety as well as comparable or increased anti-inflammatory, analgesic properties relative to NSAIDs. This review briefly deals with chemistry of NO-NSAIDs, more details are focused on biological significance, mechanism of action, and therapeutic potential of this novel class of drugs.
Acetaminophen ; analogs & derivatives ; chemistry ; pharmacology ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; pharmacology ; Aspirin ; analogs & derivatives ; chemistry ; pharmacology ; Cardiotonic Agents ; pharmacology ; Cyclooxygenase Inhibitors ; adverse effects ; pharmacology ; Flurbiprofen ; analogs & derivatives ; chemistry ; pharmacology ; Gastrointestinal Diseases ; chemically induced ; prevention & control ; Humans ; Ibuprofen ; analogs & derivatives ; chemistry ; pharmacology ; Naproxen ; analogs & derivatives ; chemistry ; pharmacology ; Nitrates ; chemistry ; pharmacology ; Nitric Oxide Donors ; pharmacology

OBJECTIVETo study the effects of Panax notoginseng saponins (PNS) on acute doxorubicin-induced myocardial injury in mice and the anti-tumor efficiency of doxorubicin.

METHODMice were given a dose of 15 mg x kg(-1) doxorubicin ip alone or in combination with 25, 50, 100 mg x kg(-1) PNS ig, 5 days before doxorubicin administration and following 3 days. Cardiotoxic effects were measured by serum levels of dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) and activities of antioxidant enzymes in heart tissue. In vitro experiments were performed using embryonic rat heart cell H9C2 to assess the protective effect of PNS (6.25-100 mg x L(-1)) against doxorubicin on cell viability. Anti-tumor efficiency of doxorubicin was evaluated by cytotoxic experiments using three cancer cell lines.

RESULTPretreatment with PNS significantly lowered the levels of serum LDH, CK and CK-MB, and normalized myocardial superoxide dismutase, glutathione peroxidase and catalase activities. PNS also attenuated the inhibitory effect of doxorubicin on the viability of H9C2 cells, but did not compromise its inhibitory effect on proliferation of cancer cells.

CONCLUSIONPNS was demonstrated to attenuate doxorubicin-induced myocardial damage without compromising its anti-tumor activity.

Animals ; Cardiotonic Agents ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Creatine Kinase ; blood ; Creatine Kinase, MB Form ; blood ; Doxorubicin ; adverse effects ; pharmacology ; Ginsenosides ; isolation & purification ; pharmacology ; Herb-Drug Interactions ; Humans ; Lactate Dehydrogenases ; blood ; Male ; Mice ; Mice, Inbred ICR ; Myocytes, Cardiac ; cytology ; drug effects ; Panax notoginseng ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats