phenanthrenes and Cardiovascular-Diseases

Triptolide (TPL), the active component of Tripterygium wilfordii Hook F (Twhf) has been used to treat cancer and bone loss conditions for over two hundred years in traditional Chinese medicine (TCM). In this paper, we reviewed the specific molecular mechanisms in the treatment of cancer, bone loss and cardiovascular disease. In addition, we analyze the toxicity of TPL and collect some optimized derivatives extracted from TPL. Although positive results were obtained in most cell culture and animal studies, further studies are needed to substantiate the beneficial effects of TPL.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Arthritis, Rheumatoid; Autophagy; Cardiovascular Diseases; Diterpenes; Epoxy Compounds; Humans; Medicine, Chinese Traditional; Neoplasms; Osteoporosis; Phenanthrenes; Plant Extracts; Signal Transduction; Tripterygium

Salvia miltiorrhiza Bunge (Danshen), a famous traditional Chinese herb, has been used clinically for the treatment of various diseases for centuries. Document data showed that tanshinones, a class of lipophilic abietane diterpenes rich in this herb, possess multiple biological effects in vitro and in vivo models. Among which, 15,16-dihydrotanshinone I (DHT) has received much attention in recent years. In this systematical review, we carefully selected, analyzed, and summarized high-quality publications related to pharmacological effects and the underlying mechanisms of DHT. DHT has anti-cancer, cardiovascular protective, anti-inflammation, anti-Alzheimer's disease, and other effects. Furthermore, several molecules such as hypoxia-inducible factor (HIF-1α), human antigen R (HuR), acetylcholinesterase (AchE), etc. have been identified as the potential targets for DHT. The diverse pharmacological activities of DHT provide scientific evidence for the local and traditional uses of Salvia miltiorrhiza Bunge. We concluded that DHT might serve as a lead compound for drug discovery in related diseases while further in-depth investigations are still needed.

Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Biological Products; Cardiovascular Diseases; Furans; Humans; Neuroprotective Agents; Phenanthrenes; Quinones; Salvia miltiorrhiza

To further evaluate the scope and mechanism of potential cardiotoxicity associated with the antimalarial drug halofantrine, case reports submitted to the US Food and Drug Administration Spontaneous Reporting System were examined. Because halofantrine was associated with electrocardiographic prolongation of the QT interval and ventricular arrhythmias, in vitro cardiac electrophysiologic studies (isolated perfused cardiac model and isolated ventricular myocytes) were conducted to test the hypothesis that halofantrine or its metabolite is responsible for cardiotoxicity.. Although it is difficult to ascertain causality and to estimate overall incidence, a significant number of adverse events related to the cardiovascular system were reported, including QT interval prolongation, life-threatening arrhythmias, and sudden death. The effect of halofantrine and its active metabolite (N-desbutylhalofantrine) on repolarization were examined in an isolated perfused heart model. Results indicate that halofantrine was able to prolong the QT interval, whereas N-desbutylhalofantrine had minimal effect on the QT interval relative to baseline. In an attempt to further elucidate the mechanism of QT interval prolongation, the effects of racemic halofantrine, its stereoisomers, and N-desbutylhalofantrine on repolarizing currents in isolated ventricular myocytes were studied with use of patch-clamp techniques. Halofantrine produced a stereoselective block of the delayed rectifier potassium channel in isolated feline myocytes.. These results indicate that halofantrine is similar to quinidine and class III antiarrhythmics in its ability to prolong repolarization. We conclude that high plasma concentrations of halofantrine should be avoided, especially in women, and that N-desbutylhalofantrine may have potential as a safer antimalarial drug.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Animals; Antimalarials; Cardiovascular Diseases; Cats; Child; Child, Preschool; Disease Models, Animal; Female; Heart Conduction System; Humans; Infant; Male; Middle Aged; Myocardium; Phenanthrenes

Sodium tanshinone IIA sulfonate (STS) has been widely used by Chinese medicine practitioners for chronic cardiovascular diseases. However, its direct clinical efficacy in patients with acute coronary syndrome following percutaneous coronary intervention (PCI) has not been reported yet. The present trial aimed to investigate potential cardioprotection of STS in patients undergoing PCI for non-ST elevation acute coronary syndrome (NSTE-ACS).. In a randomized, double-blind, placebo-controlled trial, 372 patients with NSTE-ACS were randomly assigned to receive STS (n = 192) or saline (n = 180) for 2 days before and 3 days after PCI along with standard therapy. The primary endpoint was the composite incidence of major adverse cardiac events (MACEs), including death, non-fatal myocardial infarction, repeated revascularization of the target vessel, and stent thrombosis, within 30 days after PCI.. The 30-day MACEs occurred in 18.8% of the patients in the STS group and in 27.2% of the patients in the control group (P = 0.038); this difference was mostly driven by reduction of myocardial infarction incidence (17.2% vs. 26.7%, P = 0.027). Post-procedural elevation of troponin-I was also significantly lower in the STS group (26.56% vs. 47.78%, P < 0.001). Multivariable analysis identified STS as a predictor of decreased risk of MACE occurrence (odds ratio: 0.60, 95% confidence interval: 0.36 to 0.99; P = 0.045).. Addition of STS to the standard treatments recommended by the current practice guidelines in patients with NSTE-ACS undergoing PCI could reduce myocardial injury and the occurrence of short-term cardiovascular events, primarily driven by non-fatal myocardial infarction.. ChiCTR-TRC-14005182.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Double-Blind Method; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Phenanthrenes

Coronary microembolization (CME) is a prevalent cardiovascular disease, especially nowadays when percutaneous coronary intervention is widely applied. However, neither cardio-protective agents nor devices for distal protection could effectively prevent the occurrence of CME. Therefore, we aimed to develop a new drug for CME. Rats were orally administrated with different doses of Cryptotanshinone (CTS, 5, 15, 45 mg/kg) daily for 2 weeks, respectively, following CME surgery. Then cardiac function and cardiac injury were evaluated in CME rats as well as measuring oxidative stress and apoptosis in cardiomyocytes. Compared to sham group, CME operation induced cardiac dysfunction, cardiac injury, the activation of platelet and endothelium, cardiomyocyte apoptosis and oxidative stress, all of which could be dose-dependently restored by CTS pretreatment. Moreover, NF-κB signaling pathway participated in the development of CME and also in the preventive process of CTS against CME. CTS might serve as a potential and promising candidate drug to prevent the occurrence of CME.

Topics: Administration, Oral; Animals; Apoptosis; Cardiovascular Diseases; Disease Models, Animal; Embolism; Male; Myocytes, Cardiac; NF-kappa B; Oxidative Stress; Phenanthrenes; Rats; Rats, Sprague-Dawley; Signal Transduction

Inflammation may play an important role in the association between exposure to polycyclic aromatic hydrocarbons (PAHs) and atherosclerotic cardiovascular disease (ASCVD) risk. However, the underlying mechanisms remain unclear.. To investigate the association of PAHs exposure with ASCVD risk and effects of mean platelet volume (MPV) or Club cell secretory protein (CC16) on the association.. A total of 2022 subjects (689 men and 1333 women) were drawn from the baseline Wuhan residents of the Wuhan-Zhuhai Cohort study. Data on demography and the physical examination were obtained from each participant. Urinary monohydroxy PAH metabolites (OH-PAHs) levels were measured by a gas chromatography-mass spectrometry. We estimated the association between each OH-PAHs and the 10-year ASCVD risk or coronary heart disease (CHD) risk using logistic regression models, and further analyze the mediating effect of MPV or plasma CC16 on the association by using structural equation modeling.. The results of multiple logistic regression models showed that some OH-PAHs were positively associated with ASCVD risk but not CHD risk, including 2-hydroxyfluoren (β = 1.761; 95% CI: 1.194-2.597), 9-hydroxyfluoren (β = 1.470; 95% CI: 1.139-1.898), 1-hydroxyphenanthrene (β = 1.480; 95% CI: 1.008-2.175) and ΣOH-PAHs levels (β = 1.699; 95% CI: 1.151-2.507). The analysis of structural equation modeling shows that increased MPV and increased plasma CC16 levels contributed 13.6% and 15.1%, respectively, to the association between PAHs exposure and the 10-year ASCVD risk (p < 0.05).. Exposure to PAHs may increase the risk of atherosclerosis, which was partially mediated by MPV or CC16.

Topics: Cardiovascular Diseases; China; Cohort Studies; Environmental Exposure; Female; Gas Chromatography-Mass Spectrometry; Humans; Inflammation; Logistic Models; Male; Mean Platelet Volume; Middle Aged; Phenanthrenes; Polycyclic Aromatic Hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) are environmental and occupational carcinogens produced by the incomplete combustion of organic materials, such as coal and petroleum product combustion, tobacco smoking, and food cooking, that may be significant contributors to the burden of cardiovascular disease in human populations. The purpose of this study was to investigate associations between ten monohydroxy urinary metabolites of four PAHs and three serum biomarkers of cardiovascular disease (fibrinogen, homocysteine, and white blood cell count). Using data on 3219 participants aged 20 years and older from the National Health and Nutrition Examination Survey (NHANES) 2001-2004 dataset, the associations between PAH metabolites and serum inflammatory markers were analyzed using the Spearman correlations and multiple linear regression modeling. The PAH metabolites of naphthalene, fluorene, phenanthrene, and pyrene each showed both positive and negative correlations with homocysteine, fibrinogen, and white blood cell count (correlation coefficient range: -0.077-0.143) in nonsmoking participants. Using multiple linear regression models adjusted for age, gender, race/ethnicity, and body mass index, estimates of weighted geometric means of inflammatory marker levels were not significantly different between high and low levels (75th vs. 25th percentiles) for all PAH metabolites in nonsmoking subjects. The results of this study do not provide evidence for a relationship between PAH exposure (as measured by urinary levels of PAH metabolites) and serum biomarkers of cardiovascular disease after controlling for tobacco use.

Topics: Adult; Aged; Biomarkers; Cardiovascular Diseases; Female; Fibrinogen; Fluorenes; Homocysteine; Humans; Leukocyte Count; Linear Models; Male; Middle Aged; Naphthalenes; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Pyrenes; United States

The association between background, enduring environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and cardiovascular diseases has not been well studied in the general population. In this study, we used the National Health and Nutrition Examination Survey (NHANES) 2001-2004 to investigate the associations between eight monohydroxy PAHs (OH-PAHs) and self-report CVD. In a logistic regression model adjusting for cigarette smoking and other covariates, phenanthrene metabolite, 2-hydroxyphennathrene (2-PHEN), was significantly associated with self-report CVD. Compared to subjects within the lowest tertile of 2-PHEN, subjects within the middle and highest tertiles had higher self-report CVD (the 2nd tertile: AOR=1.29, 95%CI: 0.97-1.72; the 3rd tertile: AOR=1.45, 95%CI: 1.01-2.07; p for trend=0.04). In addition, fluorene metabolite (i.e. 2-hydroxyfluorene) also showed a marginally significant linear trend with self-report CVD (p for trend=0.07). Further studies are necessary to explore the associations between these highly prevalent pollutants and CVD.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Environmental Exposure; Environmental Pollution; Female; Humans; Male; Middle Aged; Nutrition Surveys; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; United States; Young Adult

Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, a famous Chinese medicine which has been used in the treatment of cardiovascular disorders for many years. Using caffeine as a probe drug, this project was designed to investigate the effect of STS on the activity of CYP1A2 in humans. Sixteen unrelated healthy volunteers were recruited for this two-phase, randomized and crossover study. The volunteers received either placebo or 60 mg day(-1) of STS injections through vein for 13 days. Pharmacokinetics of caffeine and the metabolite paraxanthine was determined by high-performance liquid chromatography. CYP1A2 activity was monitored by the ratio of paraxanthine to caffeine at 6 h in plasma. Enzyme activity analysis showed that STS significantly increased the activity of CYP1A2 by 41.1% [90% confidence interval (CI), 17.4-64.8%] (p = 0.036). The area under the curve [AUC((0-24h))] of caffeine significantly decreased by 13.3% [90% CI = 7.0-19.6%] (p = 0.005) with 13 days of treatment of STS. AUC((0-24h)) of paraxanthine significantly increased by 17.4% [90% CI = 4.3-30.5%] (p = 0.035). No significant difference was found for other parameters of caffeine and paraxanthine between two phases. STS has significantly induced the activity of CYP1A2 in vivo. Simultaneously, AUC((0-24h)) of caffeine and paraxanthine were significantly affected by STS. The findings have provided some useful information for safe and effective usage of STS in clinic.

Topics: Adolescent; Adult; Caffeine; Cardiovascular Diseases; Cytochrome P-450 CYP1A2; Enzyme Activation; Humans; Male; Phenanthrenes; Theophylline; Time Factors

The pathogenesis of sepsis is mediated in part by bacterial endotoxin, which stimulates macrophages/monocytes to sequentially release early (e.g., TNF, IL-1, and IFN-gamma) and late (e.g., high mobility group box 1 (HMGB1) protein) proinflammatory cytokines. The recent discovery of HMGB1 as a late mediator of lethal sepsis has prompted investigation for development of new experimental therapeutics. We found that many steroidal drugs (such as dexamethasone and cortisone) and nonsteroidal anti-inflammatory drugs (such as aspirin, ibuprofen, and indomethacin) failed to influence endotoxin-induced HMGB1 release even at superpharmacological concentrations (up to 10-25 microM). However, several steroid-like pigments (tanshinone I, tanshinone IIA, and cryptotanshinone) of a popular Chinese herb, Danshen (Salvia miltiorrhiza), dose dependently attenuated endotoxin-induced HMGB1 release in macrophage/monocyte cultures. A water-soluble tanshinone IIA sodium sulfonate derivative (TSNIIA-SS), which has been widely used as a Chinese medicine for patients with cardiovascular disorders, selectively abrogated endotoxin-induced HMGB1 cytoplasmic translocation and release in a glucocorticoid receptor-independent manner. Administration of TSNIIA-SS significantly protected mice against lethal endotoxemia and rescued mice from lethal sepsis even when the first dose was given 24 h after the onset of sepsis. The therapeutic effects were partly attributable to attenuation of systemic accumulation of HMGB1 (but not TNF and NO) and improvement of cardiovascular physiologic parameters (e.g., decrease in total peripheral vascular resistance and increase in cardiac stroke volume) in septic animals. Taken together, these data re-enforce the pathogenic role of HMGB1 in lethal sepsis, and support a therapeutic potential for TSNIIA-SS in the treatment of human sepsis.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Cytokines; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Endotoxemia; High Mobility Group Proteins; HMGB1 Protein; Humans; Male; Mice; Mice, Inbred BALB C; Phenanthrenes; Protein Transport; Rats; Rats, Sprague-Dawley; Repressor Proteins; Stroke Volume; Vascular Resistance